A Biologics License Application was submitted to the FDA seeking approval of amivantamab as treatment of patients with metastatic non–small cell lung cancer harboring EGFR exon 20 insertion mutations whose disease progressed on/after platinum-based chemotherapy.
A Biologics License Application (BLA) has been submitted to the FDA, seeking approval of amivantamab (JNJ-61186372) as treatment of patients with metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations whose disease progressed on/after platinum-based chemotherapy, according to a press release.1
This BLA marks the first regulatory submission ever for the treatment of patients with NSCLC and EGFR exon 20 insertion mutations. The company plans the establish an expanded access program (EAP) for patients who may be eligible for amivantamab during the FDA’s review of the BLA.
“This submission marks an important step forward in our drive toward evolving the treatment landscape for patients with NSCLC who have EGFR exon 20 insertion mutations and for whom there are no FDA-approved targeted treatment options,” said Peter Lebowitz, MD, PhD, global therapeutic area head, Oncology, Janssen Research & Development, LLC, in a statement. “We are committed to the development of therapies like amivantamab that progress precision medicine and target specific pathways, and to providing access through expanded access programs.”
The BLA is supported by findings from the phase 1 CHRYSALIS clinical trial (NCT02609776), which was a multicenter, open-label, multicohort study evaluating the safety and efficacy of amivantamab as a single agent and in combination with the novel third-generation EGFR tyrosine kinase inhibitor lazertinib (YH25448). The study included adult patients with advanced NSCLC.
Investigators assessed the overall response rate (ORR) per RECIST 1.1 criteria, and other efficacy end points evaluated include clinical benefit rate, duration of response (DOR), and progression-free survival (PFS). Early findings for the monotherapy arm were presented during the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.2
These findings showed durable responses and a manageable safety profile of the single agent as treatment of patients with EGFR exon 20 insertion mutations. The confirmed ORR was 36% (95% CI, 21%-53%). Among the 39 evaluable patients in the 50 who enrolled in the study, 14 had partial responses (PRs). In the subset of patients post-platinum-based chemotherapy, the ORR was 41% (95% CI, 24%-61%).
The clinical benefit rate was 67% (95% CI, 50%-81%) in the overall population and 72% (95% CI, 53%-87%) in those who received prior platinum-based chemotherapy.
Most responses occurred within the first 2 months of treatment, and at a median follow-up of 4 months (range, 1-26), the median DOR was 10 months (range, 1-16). The post-platinum patient population had a median DOR of 7 months (range, 1-16), and 64% of the patients in the overall population had continuing responses at the time of data cutoff, as well as 58% of the patients who received prior platinum.
The median PFS overall was 8.3 months (95% CI, 3.0-14.8), and the post-platinum group had a median PFS of 8.6 months (95% CI, 3.7-14.8).
Overall, 96% of patients in the study experienced adverse events (AEs), which were mainly grades 1 and 2. The most common any grade AEs included rash (72%), infusion-related reaction (60%), and paronychia (34%). Grade 3 AEs were observed in 36% of patients, and serious treatment-related AEs were observed in 28%. Five patients (10%) required dose reductions dues to AEs, and 3 patients (6%) discontinued treatment altogether. Dose interruptions or modifications were not needed because no severe toxicity patterns were observed in the study. AEs led to death in 4 patients (8%), but these were not considered treatment-related.
This investigational, fully human EGFR and MET bispecific antibody had immune cell-directing activity, which targets tumors with activating and resistant EGFR and MET mutations and amplifications. Amivantamab previously received a Breakthrough Therapy designation from the FDA for this patient population in March 2020.1
1. Janssen submits application to U.S. FDA seeking approval of amivantamab for the treatment of patients with metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations. News Release. Janssen. December 3, 2020. Accessed December 3, 2020. https://bit.ly/2VwIBSH
2. Park K, John T, Kim SW, et al. Amivantamab (JNJ-61186372), an anti-EGFR-MET bispecific antibody, in patients with EGFR exon 20 insertion (exon20ins)-mutated non-small cell lung cancer (NSCLC). J Clin Oncol. 2020: 38 (suppl; abstr 9512). doi: 10.1200/JCO.2020.38.15_suppl.9512