December 2025
For more information about RYBREVANT FASPRO™, please refer to the full Prescribing Information and Important Safety Information.1
INDICATIONS
RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) and RYBREVANT® (amivantamab-vmjw) are indicated:
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
RYBREVANT FASPRO™ is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Administration-Related Reactions with RYBREVANT FASPRO™
RYBREVANT FASPRO™ can cause hypersensitivity and administration-related reactions (ARRs); signs and symptoms of ARR include dyspnea, flushing, fever, chills, chest discomfort, hypotension, and vomiting. The median time to ARR onset is approximately 2 hours.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), all Grade ARRs occurred in 13% of patients, including 0.5% Grade 3. Of the patients who experienced ARRs, 89% occurred with the initial dose (Week 1, Day 1).
Premedicate with antihistamines, antipyretics, and glucocorticoids and administer
RYBREVANT FASPRO™ as recommended. Monitor patients for any signs and symptoms of administration-related reactions during injection in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt RYBREVANT FASPRO™ injection if ARR is suspected. Resume treatment upon resolution of symptoms or permanently discontinue RYBREVANT FASPRO™ based on severity.
Infusion-Related Reactions with RYBREVANT®
RYBREVANT® can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.
RYBREVANT® with LAZCLUZE®
In MARIPOSA (n=421), IRRs occurred in 63% of patients, including Grade 3 in 5% and Grade 4 in 1% of patients. IRR-related infusion modifications occurred in 54%, dose reduction in 0.7%, and permanent discontinuation of RYBREVANT® in 4.5% of patients.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population (n=281), IRRs occurred in 50% of patients including Grade 3 (3.2%) adverse reactions. IRR-related infusion modifications occurred in 46%, and permanent discontinuation of RYBREVANT® in 2.8% of patients.
RYBREVANT® as a Single Agent
In CHRYSALIS (n=302), IRRs occurred in 66% of patients. IRRs occurred in 65% of patients on Week 1 Day 1, 3.4% on Day 2 infusion, 0.4% with Week 2 infusion, and were cumulatively 1.1% with subsequent infusions. 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range: 0.1 to 18 hours) after start of infusion. IRR-related infusion modifications occurred in 62%, and permanent discontinuation of RYBREVANT® in 1.3% of patients.
Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT® as recommended. Administer RYBREVANT® via a peripheral line on Week 1 and Week 2 to reduce the risk of IRRs. Monitor patients for signs and symptoms of IRRs in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity. If an anaphylactic reaction occurs, permanently discontinue RYBREVANT®.
Interstitial Lung Disease/Pneumonitis
RYBREVANT FASPRO™ and RYBREVANT® can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, ILD/pneumonitis occurred in 6% of patients, including Grade 3 in 1%, Grade 4 in 1.5%, and fatal cases in 1.9% of patients. 5% of patients permanently discontinued
RYBREVANT FASPRO™ and LAZCLUZE® due to ILD/pneumonitis.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT® and LAZCLUZE® due to ILD/pneumonitis.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population, ILD/pneumonitis occurred in 2.1% of patients with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% discontinued RYBREVANT® due to ILD/pneumonitis.
RYBREVANT® as a Single Agent
In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT® due to ILD/pneumonitis.
Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT FASPRO™ or RYBREVANT® and LAZCLUZE® (when applicable) in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.
Venous Thromboembolic (VTE) Events with Concomitant Use with LAZCLUZE®
RYBREVANT FASPRO™ and RYBREVANT® in combination with LAZCLUZE® can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. Without prophylactic anticoagulation, the majority of these events occurred during the first four months of treatment.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), all Grade VTE occurred in 11% of patients and 1.5% were Grade 3. 80% (n=164) of patients received prophylactic anticoagulation at study entry, with an all Grade VTE incidence of 7%. In patients who did not receive prophylactic anticoagulation (n=42), all Grade VTE occurred in 17% of patients. In total, 0.5% of patients had VTE leading to dose reductions of RYBREVANT FASPRO™ and no patients required permanent discontinuation. The median time to onset of VTEs was 95 days (range: 17 to 390).
RYBREVANT® with LAZCLUZE®
In MARIPOSA, VTEs occurred in 36% of patients including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT®, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE®; 1% of patients had VTE leading to dose reductions of RYBREVANT®, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE®; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT®, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE®. The median time to onset of VTEs was 84 days (range: 6 to 777).
Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended.
Monitor for signs and symptoms of VTE events and treat as medically appropriate. Withhold RYBREVANT FASPRO™ or RYBREVANT® and LAZCLUZE® based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT FASPRO™ or RYBREVANT® and LAZCLUZE® at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT FASPRO™ or RYBREVANT®. Treatment can continue with LAZCLUZE® at the same dose level at the discretion of the healthcare provider. Refer to the LAZCLUZE® Prescribing Information for recommended LAZCLUZE® dosage modification.
Dermatologic Adverse Reactions
RYBREVANT FASPRO™ and RYBREVANT® can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus and dry skin.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, rash occurred in 80% of patients, including Grade 3 in 17% and Grade 4 in 0.5% of patients. Rash leading to dose reduction occurred in 11% of patients, and
RYBREVANT FASPRO™ was permanently discontinued due to rash in 1.5% of patients.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, rash occurred in 86% of patients, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT® and 30% for LAZCLUZE®, rash leading to dose reductions occurred in 23% of patients for RYBREVANT® and 19% for LAZCLUZE®, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT® and 1.7% for LAZCLUZE®.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population, rash occurred in 82% of patients, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT® and 3.1% discontinued pemetrexed.
RYBREVANT® as a Single Agent
In CHRYSALIS, rash occurred in 74% of patients, including Grade 3 in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% and permanent discontinuation due to rash occurred in 0.7% of patients. Toxic epidermal necrolysis occurred in one patient (0.3%).
When initiating treatment with RYBREVANT FASPRO™ or RYBREVANT®, prophylactic and concomitant medications are recommended to reduce the risk and severity of dermatologic adverse reactions. Instruct patients to limit sun exposure during and for 2 months after treatment. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen.
If skin reactions develop, administer supportive care including topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT FASPRO™ or RYBREVANT® in combination with LAZCLUZE®, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT FASPRO™ or RYBREVANT® as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT FASPRO™ or RYBREVANT® based on severity.
Ocular Toxicity
RYBREVANT FASPRO™ and RYBREVANT® can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus and uveitis.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, all Grade ocular toxicity occurred in 13% of patients, including 0.5% Grade 3.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, ocular toxicity occurred in 16%, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT® and continue LAZCLUZE® based on severity.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population, ocular toxicity occurred in 16% of patients. All events were Grade 1 or 2.
RYBREVANT® as a Single Agent
In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients. All events were Grade 1-2.
Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO™ or RYBREVANT® based on severity.
Embryo-Fetal Toxicity
Based on animal models, RYBREVANT FASPRO™, RYBREVANT® and LAZCLUZE® can cause fetal harm when administered to a pregnant woman. Verify pregnancy status of females of reproductive potential prior to initiating RYBREVANT FASPRO™ and RYBREVANT®. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT FASPRO™ or RYBREVANT®, and for 3 weeks after the last dose of LAZCLUZE®.
ADVERSE REACTIONS
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), the most common adverse reactions (≥20%) were rash (80%), nail toxicity (58%), musculoskeletal pain (50%), fatigue (37%), stomatitis (36%), edema (34%), nausea (30%), diarrhea (22%), vomiting (22%), constipation (22%), decreased appetite (22%), and headache (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocyte count (6%), decreased sodium (5%), decreased potassium (5%), decreased albumin (4.9%), increased alanine aminotransferase (3.4%), decreased platelet count (2.4%), increased aspartate aminotransferase (2%), increased gamma-glutamyl transferase (2%), and decreased hemoglobin (2%).
Serious adverse reactions occurred in 33% of patients, with those occurring in ≥2% of patients including ILD/pneumonitis (6%); and pneumonia, VTE and fatigue (2.4% each). Death due to adverse reactions occurred in 5% of patients treated with RYBREVANT FASPRO™, including ILD/pneumonitis (1.9%), pneumonia (1.5%), and respiratory failure and sudden death (1% each).
RYBREVANT® with LAZCLUZE®
In MARIPOSA (n=421), the most common adverse reactions (ARs) (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (IRRs) (RYBREVANT®) (63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), and nausea (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%).
Serious ARs occurred in 49% of patients, with those occurring in ≥2% of patients including VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and IRRs (RYBREVANT®) (2.1% each). Fatal ARs occurred in 7% of patients due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).
RYBREVANT® with Carboplatin and Pemetrexed
In MARIPOSA-2 (n=130), the most common ARs (≥20%) were rash (72%), IRRs (59%), fatigue (51%), nail toxicity (45%), nausea (45%), constipation (39%), edema (36%), stomatitis (35%), decreased appetite (31%), musculoskeletal pain (30%), vomiting (25%), and COVID-19 (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased neutrophils (49%), decreased white blood cells (42%), decreased lymphocytes (28%), decreased platelets (17%), decreased hemoglobin (12%), decreased potassium (11%), decreased sodium (11%), increased alanine aminotransferase (3.9%), decreased albumin (3.8%), and increased gamma-glutamyl transferase (3.1%).
In MARIPOSA-2, serious ARs occurred in 32% of patients, with those occurring in >2% of patients including dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and PE (2.3%). Fatal ARs occurred in 2.3% of patients; these included respiratory failure, sepsis, and ventricular fibrillation (0.8% each).
In PAPILLON (n=151), the most common ARs (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), IRRs (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%).
In PAPILLON, serious ARs occurred in 37% of patients, with those occurring in ≥2% of patients including rash, pneumonia, ILD, PE, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified.
RYBREVANT® as a Single Agent
In CHRYSALIS (n=129), the most common ARs (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).
Serious ARs occurred in 30% of patients, with those occurring in ≥2% of patients including PE, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death.
LAZCLUZE® DRUG INTERACTIONS
Avoid concomitant use of LAZCLUZE® with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.
Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.
Please see full Prescribing Information for RYBREVANT FASPRO™, RYBREVANT® and LAZCLUZE®.
cp-491009v1
References
For more information about RYBREVANT FASPRO™, please refer to the full Prescribing Information and Important Safety Information.1
INDICATIONS
RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) and RYBREVANT® (amivantamab-vmjw) are indicated:
- in combination with LAZCLUZE® (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.
- in combination with carboplatin and pemetrexed for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor.
- in combination with carboplatin and pemetrexed for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.
- as a single agent for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA approved test, whose disease has progressed on or after platinum-based chemotherapy.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
RYBREVANT FASPRO™ is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Administration-Related Reactions with RYBREVANT FASPRO™
RYBREVANT FASPRO™ can cause hypersensitivity and administration-related reactions (ARRs); signs and symptoms of ARR include dyspnea, flushing, fever, chills, chest discomfort, hypotension, and vomiting. The median time to ARR onset is approximately 2 hours.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), all Grade ARRs occurred in 13% of patients, including 0.5% Grade 3. Of the patients who experienced ARRs, 89% occurred with the initial dose (Week 1, Day 1).
Premedicate with antihistamines, antipyretics, and glucocorticoids and administer
RYBREVANT FASPRO™ as recommended. Monitor patients for any signs and symptoms of administration-related reactions during injection in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt RYBREVANT FASPRO™ injection if ARR is suspected. Resume treatment upon resolution of symptoms or permanently discontinue RYBREVANT FASPRO™ based on severity.
Infusion-Related Reactions with RYBREVANT®
RYBREVANT® can cause infusion-related reactions (IRR) including anaphylaxis; signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. The median time to IRR onset is approximately 1 hour.
RYBREVANT® with LAZCLUZE®
In MARIPOSA (n=421), IRRs occurred in 63% of patients, including Grade 3 in 5% and Grade 4 in 1% of patients. IRR-related infusion modifications occurred in 54%, dose reduction in 0.7%, and permanent discontinuation of RYBREVANT® in 4.5% of patients.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population (n=281), IRRs occurred in 50% of patients including Grade 3 (3.2%) adverse reactions. IRR-related infusion modifications occurred in 46%, and permanent discontinuation of RYBREVANT® in 2.8% of patients.
RYBREVANT® as a Single Agent
In CHRYSALIS (n=302), IRRs occurred in 66% of patients. IRRs occurred in 65% of patients on Week 1 Day 1, 3.4% on Day 2 infusion, 0.4% with Week 2 infusion, and were cumulatively 1.1% with subsequent infusions. 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range: 0.1 to 18 hours) after start of infusion. IRR-related infusion modifications occurred in 62%, and permanent discontinuation of RYBREVANT® in 1.3% of patients.
Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT® as recommended. Administer RYBREVANT® via a peripheral line on Week 1 and Week 2 to reduce the risk of IRRs. Monitor patients for signs and symptoms of IRRs in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT® based on severity. If an anaphylactic reaction occurs, permanently discontinue RYBREVANT®.
Interstitial Lung Disease/Pneumonitis
RYBREVANT FASPRO™ and RYBREVANT® can cause severe and fatal interstitial lung disease (ILD)/pneumonitis.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, ILD/pneumonitis occurred in 6% of patients, including Grade 3 in 1%, Grade 4 in 1.5%, and fatal cases in 1.9% of patients. 5% of patients permanently discontinued
RYBREVANT FASPRO™ and LAZCLUZE® due to ILD/pneumonitis.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, ILD/pneumonitis occurred in 3.1% of patients, including Grade 3 in 1.0% and Grade 4 in 0.2% of patients. There was one fatal case of ILD/pneumonitis and 2.9% of patients permanently discontinued RYBREVANT® and LAZCLUZE® due to ILD/pneumonitis.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population, ILD/pneumonitis occurred in 2.1% of patients with 1.8% of patients experiencing Grade 3 ILD/pneumonitis. 2.1% discontinued RYBREVANT® due to ILD/pneumonitis.
RYBREVANT® as a Single Agent
In CHRYSALIS, ILD/pneumonitis occurred in 3.3% of patients, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) permanently discontinued RYBREVANT® due to ILD/pneumonitis.
Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT FASPRO™ or RYBREVANT® and LAZCLUZE® (when applicable) in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.
Venous Thromboembolic (VTE) Events with Concomitant Use with LAZCLUZE®
RYBREVANT FASPRO™ and RYBREVANT® in combination with LAZCLUZE® can cause serious and fatal venous thromboembolic (VTE) events, including deep vein thrombosis and pulmonary embolism. Without prophylactic anticoagulation, the majority of these events occurred during the first four months of treatment.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), all Grade VTE occurred in 11% of patients and 1.5% were Grade 3. 80% (n=164) of patients received prophylactic anticoagulation at study entry, with an all Grade VTE incidence of 7%. In patients who did not receive prophylactic anticoagulation (n=42), all Grade VTE occurred in 17% of patients. In total, 0.5% of patients had VTE leading to dose reductions of RYBREVANT FASPRO™ and no patients required permanent discontinuation. The median time to onset of VTEs was 95 days (range: 17 to 390).
RYBREVANT® with LAZCLUZE®
In MARIPOSA, VTEs occurred in 36% of patients including Grade 3 in 10% and Grade 4 in 0.5% of patients. On-study VTEs occurred in 1.2% of patients (n=5) while receiving anticoagulation therapy. There were two fatal cases of VTE (0.5%), 9% of patients had VTE leading to dose interruptions of RYBREVANT®, and 7% of patients had VTE leading to dose interruptions of LAZCLUZE®; 1% of patients had VTE leading to dose reductions of RYBREVANT®, and 0.5% of patients had VTE leading to dose reductions of LAZCLUZE®; 3.1% of patients had VTE leading to permanent discontinuation of RYBREVANT®, and 1.9% of patients had VTE leading to permanent discontinuation of LAZCLUZE®. The median time to onset of VTEs was 84 days (range: 6 to 777).
Administer prophylactic anticoagulation for the first four months of treatment. The use of Vitamin K antagonists is not recommended.
Monitor for signs and symptoms of VTE events and treat as medically appropriate. Withhold RYBREVANT FASPRO™ or RYBREVANT® and LAZCLUZE® based on severity. Once anticoagulant treatment has been initiated, resume RYBREVANT FASPRO™ or RYBREVANT® and LAZCLUZE® at the same dose level at the discretion of the healthcare provider. In the event of VTE recurrence despite therapeutic anticoagulation, permanently discontinue RYBREVANT FASPRO™ or RYBREVANT®. Treatment can continue with LAZCLUZE® at the same dose level at the discretion of the healthcare provider. Refer to the LAZCLUZE® Prescribing Information for recommended LAZCLUZE® dosage modification.
Dermatologic Adverse Reactions
RYBREVANT FASPRO™ and RYBREVANT® can cause severe rash including toxic epidermal necrolysis (TEN), dermatitis acneiform, pruritus and dry skin.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, rash occurred in 80% of patients, including Grade 3 in 17% and Grade 4 in 0.5% of patients. Rash leading to dose reduction occurred in 11% of patients, and
RYBREVANT FASPRO™ was permanently discontinued due to rash in 1.5% of patients.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, rash occurred in 86% of patients, including Grade 3 in 26% of patients. The median time to onset of rash was 14 days (range: 1 to 556 days). Rash leading to dose interruptions occurred in 37% of patients for RYBREVANT® and 30% for LAZCLUZE®, rash leading to dose reductions occurred in 23% of patients for RYBREVANT® and 19% for LAZCLUZE®, and rash leading to permanent discontinuation occurred in 5% of patients for RYBREVANT® and 1.7% for LAZCLUZE®.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population, rash occurred in 82% of patients, including Grade 3 (15%) adverse reactions. Rash leading to dose reductions occurred in 14% of patients, and 2.5% permanently discontinued RYBREVANT® and 3.1% discontinued pemetrexed.
RYBREVANT® as a Single Agent
In CHRYSALIS, rash occurred in 74% of patients, including Grade 3 in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% and permanent discontinuation due to rash occurred in 0.7% of patients. Toxic epidermal necrolysis occurred in one patient (0.3%).
When initiating treatment with RYBREVANT FASPRO™ or RYBREVANT®, prophylactic and concomitant medications are recommended to reduce the risk and severity of dermatologic adverse reactions. Instruct patients to limit sun exposure during and for 2 months after treatment. Advise patients to wear protective clothing and use broad spectrum UVA/UVB sunscreen.
If skin reactions develop, administer supportive care including topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. For patients receiving RYBREVANT FASPRO™ or RYBREVANT® in combination with LAZCLUZE®, withhold, reduce the dose, or permanently discontinue both drugs based on severity. For patients receiving RYBREVANT FASPRO™ or RYBREVANT® as a single agent or in combination with carboplatin and pemetrexed, withhold, dose reduce or permanently discontinue RYBREVANT FASPRO™ or RYBREVANT® based on severity.
Ocular Toxicity
RYBREVANT FASPRO™ and RYBREVANT® can cause ocular toxicity including keratitis, blepharitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, eye pruritus and uveitis.
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3, all Grade ocular toxicity occurred in 13% of patients, including 0.5% Grade 3.
RYBREVANT® with LAZCLUZE®
In MARIPOSA, ocular toxicity occurred in 16%, including Grade 3 or 4 ocular toxicity in 0.7% of patients. Withhold, reduce the dose, or permanently discontinue RYBREVANT® and continue LAZCLUZE® based on severity.
RYBREVANT® with Carboplatin and Pemetrexed
Based on the pooled safety population, ocular toxicity occurred in 16% of patients. All events were Grade 1 or 2.
RYBREVANT® as a Single Agent
In CHRYSALIS, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients. All events were Grade 1-2.
Promptly refer patients presenting with new or worsening eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT FASPRO™ or RYBREVANT® based on severity.
Embryo-Fetal Toxicity
Based on animal models, RYBREVANT FASPRO™, RYBREVANT® and LAZCLUZE® can cause fetal harm when administered to a pregnant woman. Verify pregnancy status of females of reproductive potential prior to initiating RYBREVANT FASPRO™ and RYBREVANT®. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise patients of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of RYBREVANT FASPRO™ or RYBREVANT®, and for 3 weeks after the last dose of LAZCLUZE®.
ADVERSE REACTIONS
RYBREVANT FASPRO™ with LAZCLUZE®
In PALOMA-3 (n=206), the most common adverse reactions (≥20%) were rash (80%), nail toxicity (58%), musculoskeletal pain (50%), fatigue (37%), stomatitis (36%), edema (34%), nausea (30%), diarrhea (22%), vomiting (22%), constipation (22%), decreased appetite (22%), and headache (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocyte count (6%), decreased sodium (5%), decreased potassium (5%), decreased albumin (4.9%), increased alanine aminotransferase (3.4%), decreased platelet count (2.4%), increased aspartate aminotransferase (2%), increased gamma-glutamyl transferase (2%), and decreased hemoglobin (2%).
Serious adverse reactions occurred in 33% of patients, with those occurring in ≥2% of patients including ILD/pneumonitis (6%); and pneumonia, VTE and fatigue (2.4% each). Death due to adverse reactions occurred in 5% of patients treated with RYBREVANT FASPRO™, including ILD/pneumonitis (1.9%), pneumonia (1.5%), and respiratory failure and sudden death (1% each).
RYBREVANT® with LAZCLUZE®
In MARIPOSA (n=421), the most common adverse reactions (ARs) (≥20%) were rash (86%), nail toxicity (71%), infusion-related reactions (IRRs) (RYBREVANT®) (63%), musculoskeletal pain (47%), stomatitis (43%), edema (43%), VTE (36%), paresthesia (35%), fatigue (32%), diarrhea (31%), constipation (29%), COVID-19 (26%), hemorrhage (25%), dry skin (25%), decreased appetite (24%), pruritus (24%), and nausea (21%). The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased albumin (8%), decreased sodium (7%), increased ALT (7%), decreased potassium (5%), decreased hemoglobin (3.8%), increased AST (3.8%), increased GGT (2.6%), and increased magnesium (2.6%).
Serious ARs occurred in 49% of patients, with those occurring in ≥2% of patients including VTE (11%), pneumonia (4%), ILD/pneumonitis and rash (2.9% each), COVID-19 (2.4%), and pleural effusion and IRRs (RYBREVANT®) (2.1% each). Fatal ARs occurred in 7% of patients due to death not otherwise specified (1.2%); sepsis and respiratory failure (1% each); pneumonia, myocardial infarction, and sudden death (0.7% each); cerebral infarction, pulmonary embolism (PE), and COVID-19 infection (0.5% each); and ILD/pneumonitis, acute respiratory distress syndrome (ARDS), and cardiopulmonary arrest (0.2% each).
RYBREVANT® with Carboplatin and Pemetrexed
In MARIPOSA-2 (n=130), the most common ARs (≥20%) were rash (72%), IRRs (59%), fatigue (51%), nail toxicity (45%), nausea (45%), constipation (39%), edema (36%), stomatitis (35%), decreased appetite (31%), musculoskeletal pain (30%), vomiting (25%), and COVID-19 (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased neutrophils (49%), decreased white blood cells (42%), decreased lymphocytes (28%), decreased platelets (17%), decreased hemoglobin (12%), decreased potassium (11%), decreased sodium (11%), increased alanine aminotransferase (3.9%), decreased albumin (3.8%), and increased gamma-glutamyl transferase (3.1%).
In MARIPOSA-2, serious ARs occurred in 32% of patients, with those occurring in >2% of patients including dyspnea (3.1%), thrombocytopenia (3.1%), sepsis (2.3%), and PE (2.3%). Fatal ARs occurred in 2.3% of patients; these included respiratory failure, sepsis, and ventricular fibrillation (0.8% each).
In PAPILLON (n=151), the most common ARs (≥20%) were rash (90%), nail toxicity (62%), stomatitis (43%), IRRs (42%), fatigue (42%), edema (40%), constipation (40%), decreased appetite (36%), nausea (36%), COVID-19 (24%), diarrhea (21%), and vomiting (21%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased albumin (7%), increased alanine aminotransferase (4%), increased gamma-glutamyl transferase (4%), decreased sodium (7%), decreased potassium (11%), decreased magnesium (2%), and decreases in white blood cells (17%), hemoglobin (11%), neutrophils (36%), platelets (10%), and lymphocytes (11%).
In PAPILLON, serious ARs occurred in 37% of patients, with those occurring in ≥2% of patients including rash, pneumonia, ILD, PE, vomiting, and COVID-19. Fatal adverse reactions occurred in 7 patients (4.6%) due to pneumonia, cerebrovascular accident, cardio-respiratory arrest, COVID-19, sepsis, and death not otherwise specified.
RYBREVANT® as a Single Agent
In CHRYSALIS (n=129), the most common ARs (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).
Serious ARs occurred in 30% of patients, with those occurring in ≥2% of patients including PE, pneumonitis/ILD, dyspnea, musculoskeletal pain, pneumonia, and muscular weakness. Fatal adverse reactions occurred in 2 patients (1.5%) due to pneumonia and 1 patient (0.8%) due to sudden death.
LAZCLUZE® DRUG INTERACTIONS
Avoid concomitant use of LAZCLUZE® with strong and moderate CYP3A4 inducers. Consider an alternate concomitant medication with no potential to induce CYP3A4.
Monitor for adverse reactions associated with a CYP3A4 or BCRP substrate where minimal concentration changes may lead to serious adverse reactions, as recommended in the approved product labeling for the CYP3A4 or BCRP substrate.
Please see full Prescribing Information for RYBREVANT FASPRO™, RYBREVANT® and LAZCLUZE®.
cp-491009v1
References
- RYBREVANT FASPRO™ [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
- George S, Bourlon MT, Overman MJ, et al. Systematic literature review of intravenous versus subcutaneous administration of oncology therapies: a clinical, economic and patient perspective. Cancer Treat Rev. 2025;139:102974. doi:10.1016/j.ctrv.2025.102974
- Bittner B, Richter W, Schmidt J. Subcutaneous administration of biotherapeutics: an overview of current challenges and opportunities. BioDrugs. 2018;32(5):425-440. doi:10.1007/s40259-018-0295-0
- Aguiar-Ibáñez R, Fotheringham I, Mittal L, et al. Differences between intravenous and subcutaneous modes of administration in oncology from the patient, healthcare provider, and healthcare system perspectives: a systematic review. Adv Ther. 2024;41(12):4396-4417. doi:10.1007/s12325-024-02985-9
Findings from first-ever quadruplet therapy study with subcutaneous DARZALEX FASPRO® showed 60 percent reduction in risk of disease progression or death
New regimen solidifies DARZALEX FASPRO® as a foundational frontline therapy in multiple myeloma with potential to significantly delay disease progression
July 30, 2024
HORSHAM, Pa., July 30, 2024 – Johnson & Johnson (NYSE:JNJ) announced today that the U.S. Food and Drug Administration (FDA) approved DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for induction and consolidation in patients with newly diagnosed multiple myeloma (NDMM) who are eligible for an autologous stem cell transplant (ASCT).1 Patients will have the opportunity to receive this DARZALEX FASPRO®-based quadruplet therapy at initial diagnosis, providing them with a new treatment that may significantly improve outcomes.
This approval is supported by data from the Phase 3 PERSEUS study evaluating DARZALEX FASPRO® in a regimen that included D-VRd induction and consolidation therapy compared to bortezomib, lenalidomide and dexamethasone (VRd) during induction and consolidation in patients with NDMM eligible for ASCT.1 Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone.1
“Multiple myeloma has a highly varied clinical course among patients and in each individual patient, and there is a continued need for innovation and therapies that employ different targets and combinations to provide patients with treatment options at diagnosis and throughout the course of their disease,” said Amrita Y. Krishnan, M.D., Professor and Director of the Judy and Bernard Briskin Multiple Myeloma Center, City of Hope.* “The efficacy data supporting this new quadruplet regimen, combined with its established safety and tolerability profile, provide compelling evidence that adding D-VRd upon initial diagnosis as compared to VRd can deepen responses and prolong remissions in the context of autologous stem cell transplantation.”
Findings from the PERSEUS study demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), with D-VRd reducing the risk of disease progression or death by 60 percent compared to VRd (HR [95% CI]: 0.40 [0.29, 0.57]; p-value < 0.0001).1 Treatment with D-VRd induction and consolidation resulted in deeper responses at the end of consolidation compared to VRd: minimal residual disease (MRD) negativity rates of 57.5 percent vs. 32.5 percent, and MRD-negativity rates in patients with complete response (CR) or better of 76.6 percent vs. 58.5 percent, respectively.1
“This latest indication for DARZALEX FASPRO-based quadruplet therapy demonstrated a clinically significant reduction in disease progression or death during first-line treatment when patients are likely to experience their deepest responses,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson. “Today’s approval embodies our commitment to setting new standards of care for patients newly diagnosed with multiple myeloma who are transplant eligible.”
The overall safety profile of D-VRd was consistent with the known safety profiles for DARZALEX FASPRO® and VRd.1 The most common adverse reactions (≥20%) in patients with multiple myeloma who received D-VRd are peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.1
About the PERSEUS Study
The PERSEUS study is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for ASCT. Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm.2 The study is being conducted in 14 countries in Europe and Australia.
About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.3 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.4 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.5 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.6 People with multiple myeloma have a 5-year survival rate of 59.8 percent.6 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.7,8
About DARZALEX FASPRO®
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.1 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.
For more information, visit https://www.darzalexhcp.com.
DARZALEX FASPRO® INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.
Systemic Reactions
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.
Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®.
Local Reactions
In this pooled safety population, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management.
Neutropenia
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.
Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose.
The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.
Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.
Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®.
Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, peripheral edema, musculoskeletal pain, and rash.
The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.
Please click here to read full Prescribing Information for DARZALEX FASPRO®.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.
Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments.
*Dr. Amrita Y. Krishnan has provided consulting, advisory, and speaking services to Johnson & Johnson; she has not been paid for any media work.
###
Footnotes
1 DARZALEX FASPRO® U.S. Prescribing Information.
2 Pieter Sonneveld, Dimopoulos MA, Boccadoro M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. The New England Journal of Medicine. Accessed July 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2312054
3 Rajkumar SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification and Management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178
4 National Cancer Institute. Plasma Cell Neoplasms. Accessed July 2024. Available at: https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq
5 Multiple Myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms & Treatments. Accessed July 2024. Available at: https://www.cancercenter.com/cancer-types/multiple-myeloma
6 American Cancer Society. Myeloma Cancer Statistics. Accessed July 2024. Available at: https://cancerstatisticscenter.cancer.org/types/myeloma
7 American Cancer Society. What is Multiple Myeloma? Accessed July 2024. Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html
8 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. Accessed July 2024. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html
Media contact:
Jessica Szramiak
1-773-519-0631
Satu Glawe
+49 172-294-6264
Investor contact:Raychel Kruper
[email protected]
U.S. medical inquiries:+1 800 526-7736
New regimen solidifies DARZALEX FASPRO® as a foundational frontline therapy in multiple myeloma with potential to significantly delay disease progression
July 30, 2024
HORSHAM, Pa., July 30, 2024 – Johnson & Johnson (NYSE:JNJ) announced today that the U.S. Food and Drug Administration (FDA) approved DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for induction and consolidation in patients with newly diagnosed multiple myeloma (NDMM) who are eligible for an autologous stem cell transplant (ASCT).1 Patients will have the opportunity to receive this DARZALEX FASPRO®-based quadruplet therapy at initial diagnosis, providing them with a new treatment that may significantly improve outcomes.
This approval is supported by data from the Phase 3 PERSEUS study evaluating DARZALEX FASPRO® in a regimen that included D-VRd induction and consolidation therapy compared to bortezomib, lenalidomide and dexamethasone (VRd) during induction and consolidation in patients with NDMM eligible for ASCT.1 Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone.1
“Multiple myeloma has a highly varied clinical course among patients and in each individual patient, and there is a continued need for innovation and therapies that employ different targets and combinations to provide patients with treatment options at diagnosis and throughout the course of their disease,” said Amrita Y. Krishnan, M.D., Professor and Director of the Judy and Bernard Briskin Multiple Myeloma Center, City of Hope.* “The efficacy data supporting this new quadruplet regimen, combined with its established safety and tolerability profile, provide compelling evidence that adding D-VRd upon initial diagnosis as compared to VRd can deepen responses and prolong remissions in the context of autologous stem cell transplantation.”
Findings from the PERSEUS study demonstrated a significant improvement in the primary endpoint of progression-free survival (PFS), with D-VRd reducing the risk of disease progression or death by 60 percent compared to VRd (HR [95% CI]: 0.40 [0.29, 0.57]; p-value < 0.0001).1 Treatment with D-VRd induction and consolidation resulted in deeper responses at the end of consolidation compared to VRd: minimal residual disease (MRD) negativity rates of 57.5 percent vs. 32.5 percent, and MRD-negativity rates in patients with complete response (CR) or better of 76.6 percent vs. 58.5 percent, respectively.1
“This latest indication for DARZALEX FASPRO-based quadruplet therapy demonstrated a clinically significant reduction in disease progression or death during first-line treatment when patients are likely to experience their deepest responses,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson. “Today’s approval embodies our commitment to setting new standards of care for patients newly diagnosed with multiple myeloma who are transplant eligible.”
The overall safety profile of D-VRd was consistent with the known safety profiles for DARZALEX FASPRO® and VRd.1 The most common adverse reactions (≥20%) in patients with multiple myeloma who received D-VRd are peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.1
About the PERSEUS Study
The PERSEUS study is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for ASCT. Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm.2 The study is being conducted in 14 countries in Europe and Australia.
About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.3 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.4 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.5 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.6 People with multiple myeloma have a 5-year survival rate of 59.8 percent.6 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.7,8
About DARZALEX FASPRO®
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.1 It is the only subcutaneous CD38-directed antibody approved to treat patients with multiple myeloma. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.
For more information, visit https://www.darzalexhcp.com.
DARZALEX FASPRO® INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:
- In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
- In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.
WARNINGS AND PRECAUTIONS
Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.
Systemic Reactions
In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.
Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®.
Local Reactions
In this pooled safety population, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management.
Neutropenia
Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.
Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose.
The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.
Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.
Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®.
Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.
ADVERSE REACTIONS
In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, peripheral edema, musculoskeletal pain, and rash.
The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.
Please click here to read full Prescribing Information for DARZALEX FASPRO®.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.
Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections Janssen Research & Development, LLC, Janssen Biotech, Inc. and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments.
*Dr. Amrita Y. Krishnan has provided consulting, advisory, and speaking services to Johnson & Johnson; she has not been paid for any media work.
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Footnotes
1 DARZALEX FASPRO® U.S. Prescribing Information.
2 Pieter Sonneveld, Dimopoulos MA, Boccadoro M, et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. The New England Journal of Medicine. Accessed July 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2312054
3 Rajkumar SV. Multiple Myeloma: 2020 Update on Diagnosis, Risk-Stratification and Management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178
4 National Cancer Institute. Plasma Cell Neoplasms. Accessed July 2024. Available at: https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq
5 Multiple Myeloma. City of Hope, 2022. Multiple Myeloma: Causes, Symptoms & Treatments. Accessed July 2024. Available at: https://www.cancercenter.com/cancer-types/multiple-myeloma
6 American Cancer Society. Myeloma Cancer Statistics. Accessed July 2024. Available at: https://cancerstatisticscenter.cancer.org/types/myeloma
7 American Cancer Society. What is Multiple Myeloma? Accessed July 2024. Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html
8 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. Accessed July 2024. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html
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