FDA issues response letter for J&J's NSCLC drug

The CRL is related to observations as part of a standard pre-approval inspection at a manufacturing facility. The CRL is unrelated to the product formulation, or the efficacy and safety data submitted in the regulatory application, and the FDA has not requested any additional clinical studies. The currently approved intravenous (IV) formulation of Rybrevant (amivantamab-vmjw) is not impacted by the CRL

“We’re working closely with the FDA to bring SC amivantamab to patients as quickly as possible, and are confident in our path to resolution,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D. Global Therapeutic Area Head, Oncology, Innovative Medicine, Johnson & Johnson. ““Backed by interim overall survival data showing a strong favorable trend compared to osimertinib, we believe strongly in the robust efficacy and safety of Rybrevant  – both as a standalone treatment and in combination with Lazcluze – for EGFR-mutated advanced lung cancer. We’re proud to have helped so many patients in the front-line setting already with Rybrevant  and look forward to further expanding treatment options with our subcutaneous formulation pending regulatory review and approval.”

The BLA is based on the Phase III PALOMA-3 study results presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology. In August 2024, the FDA granted Priority Review for the BLA for SC amivantamab as a treatment for patients with NSCLC with EGFR exon 19 deletions (ex19del) or L858R substitution mutations. Rybrevant  is currently approved in over 60 countries worldwide.

About the PALOMA-3 Study: PALOMA-3 (NCT05388669), which enrolled 418 patients, is a randomized, open-label Phase III study evaluating the pharmacokinetics (PK), efficacy and safety of subcutaneous amivantamab (administered via manual injection) combined with lazertinib compared to IV amivantamab and Lazcluze (lazertinib) in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and chemotherapy. The co-primary PK endpoints of the study were trough concentration (Ctrough on Cycle [C] 2 Day [D] 1 or C4D1) and C2 area under the curve (AUCD1-D15). Descriptive efficacy outcome measures were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Prophylactic anticoagulation was recommended for the first four months of treatment.

About the MARIPOSA Study
MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase III study evaluating Rybrevant  in combination with Lazcluse versus osimertinib and versus Lazcluse alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by blinded independent central review (BICR). Secondary endpoints include OS, ORR, duration of response (DOR), second progression-free survival (PFS2) and intracranial PFS. The combination therapy showed a significant PFS improvement and a favorable OS trend, with a safety profile consistent with known effects of the individual treatments. Overall survival will continue to be assessed with longer term follow-up as a key secondary endpoint.

Citation:  ClinicalTrials.gov. A Study of Lacluze  With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed December 2024.