On March 1, 2024, amivantamab-vmjw (Rybrevant) was approved for use with carboplatin and pemetrexed for first-line treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by a U.S. Food and Drug Administration (FDA)-approved test.¹

Amivantamab was also granted regular approval as a single agent for patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, who had disease progression on or after platinum-based chemotherapy (accelerated approval granted in May 2021).

Supporting Efficacy Data

Approval in the first-line setting was based on the open-label PAPILLON trial (ClinicalTrials.gov identifier NCT04538664), in which 308 patients were randomly assigned to receive amivantamab plus carboplatin/pemetrexed (n = 153) or carboplatin/pemetrexed (n = 158). Amivantamab was given at weight-based intravenous doses once weekly through 4 weeks and then every 3 weeks until disease progression or unacceptable toxicity. Carboplatin was given every 3 weeks for up to 12 weeks. Pemetrexed was given every 3 weeks until disease progression or unacceptable toxicity.

Median progression-free survival on blinded independent central review was 11.4 months (95% confidence interval [CI] = 9.8–13.7 months) in the amivantamab group vs 6.7 months (95% CI = 5.6–7.3 months) in the control group (hazard ratio = 0.40, 95% CI = 0.30–0.53, P < .0001).

How It Is Used

The recommended amivantamab dosage is 1,400 mg (body weight < 80 kg) or 1,750 mg (≥ 80 kg) once weekly through 4 weeks and then 1,750 mg (< 80 kg) or 2,100 mg (≥ 80 kg) every 3 weeks until disease progression or unacceptable toxicity. The recommended dose of carboplatin is AUC 5 every 3 weeks for up to 12 weeks, and the recommended dose of pemetrexed is 500 mg/m² every 3 weeks until disease progression or unacceptable toxicity. The order of treatment when drugs are given on the same day is pemetrexed first, then carboplatin, then amivantamab. Product labeling provides instructions on premedication and dosage modification, including amivantamab dose reduction, for adverse reactions including infusion-related reactions, interstitial lung disease/pneumonitis, and dermatologic reactions.

Safety Profile

In PAPILLON, the most common adverse events of any grade in the amivantamab group were rash (90% vs 19% in control group), nail toxicity (62% vs 3%), stomatitis (43% vs 11%), infusion-related reaction (42% vs 1%), fatigue (42% vs 45%), edema (40% vs 19%), and constipation (40% vs 30%). The most common grade 3 or 4 adverse events in the amivantamab group included rash (19%), nail toxicity (7%), fatigue (6%), and pneumonia (5%). The most common grade 3 or 4 laboratory abnormalities were decreased neutrophils (17%) and decreased white blood cell counts (17%).

In the amivantamab group, serious adverse events occurred in 37% of patients, most commonly (≥ 2%) rash, pneumonia, interstitial lung disease, pulmonary embolism, vomiting, and COVID-19. Adverse events led to discontinuation of amivantamab in 11% of patients, most commonly (≥ 1%) rash and interstitial lung disease. Fatal adverse events occurred in seven patients (4.6%), including pneumonia, cerebrovascular accident, cardiorespiratory arrest, COVID-19, sepsis, and death not otherwise specified.

Amivantamab has warnings/precautions for infusion-related reactions, interstitial lung disease/pneumonitis, dermatologic reactions, ocular toxicity, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving amivantamab.

REFERENCE

1. Rybrevant (amivantamab-vmjw) injection, for intravenous use, prescribing information, Janssen Pharmaceutical Companies, March 2024. Available at https://www. rybrevanthcp.com. Accessed March 18, 2024.