FDA Approval Sought for Amivantamab for Metastatic EGFR Exon 20–Positive NSCLC


December 3, 2020 — A biologics license application has been submitted to the FDA for the EGFR-MET bispecific antibody amivantamab for the treatment of patients with metastatic non–small cell lung cancer with EGFR exon 20 insertion mutations who have progressed on or following a platinum-based chemotherapy.

A biologics license application (BLA) has been submitted to the FDA for the EGFR-MET bispecific antibody amivantamab (JNJ-61186372; JNJ-6372) for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations who have progressed on or following a platinum-based chemotherapy.1

Notably, the BLA serves as the first regulatory submission for the treatment of patients with NSCLC whose tumors harbor EGFR exon 20 insertion mutations, according to The Janssen Pharmaceutical Companies of Johnson & Johnson.

The application was based on findings from the single-agent arm of the phase 1 CHRYSALIS trial (NCT02609776). Early data from the trial presented during the 2020 ASCO Virtual Scientific Program showed that amivantamab elicited an overall response rate (ORR) of 36% (95% CI, 21%-53%) in all patients analyzed with 14 of 39 patients achieving a partial response (PR) to treatment.2 Moreover, the ORR was 41% (95% CI, 24%-61%) in patients who previously received platinum-based chemotherapy.

“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,” Peter Lebowitz, MD, PhD, global therapeutic area head of Oncology at Janssen Research & Development, LLC. “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 two-part phase 1 trial enrolled patients with metastatic or unresectable NSCLC who progressed on previous therapy or were ineligible for or refused current therapies. Patients had to have an ECOG performance status of 0 or 1. For part 1, patients needed to have evaluable disease; they had to have measurable disease to enroll to the second part of the trial.

Additionally, all patients in part 2 needed to have tumors that harbored activating EGFR or MET mutations or amplifications and have progressed on standard-of-care treatment. Patients with previously definitively treated brain metastases were permitted.

Part 1 of the trial was a dose-escalation design, where patients were given 140 mg, 350 mg, 700 mg, 1050 mg, 1400 mg, up to 1750 mg of the agent. The primary objective of this phase of the research was to establish the recommended phase 2 dose, which was established to be 1050 mg, but 1400 mg for those who were greater than 80 kg. The agent was administered intravenously once weekly for the first treatment cycle and then biweekly thereafter.

Several cohorts of patients were examined, but data from an analysis of the cohort of patients with EGFR exon 20 insertion mutations was presented during the meeting. Across both parts of the trial, a total of 50 of these patients received at least 1 dose of amivantamab at the recommended dose. Of these patients, 39 were determined to be evaluable for response and 13 distinct EGFR exon 20 insertion mutations were identified. Seventy-four percent of the evaluable patients had received previous platinum-based chemotherapy in the metastatic setting, 6 were treatment naïve, and 4 had been given other treatments such as EGFR TKIs or a VEGF inhibitor.

Amivantamab resulted in a reduction in target lesions in patients who previously received platinum-based chemotherapy, as well as those who never received treatment before. Notably, the agent showcased activity across all the distinct mutations identified. The clinical benefit rate (CBR) with amivantamab was 67% (95% CI, 50-81) for all patients; it was a bit higher, at 72%, (95% CI, 53-87) in post-platinum patients.

Responses were found to occur within 2 months of treatment with the agent. At a median follow-up of 4 months, the median duration of response (DOR) was reported to be 10 months in all patients evaluable for assessment. In post-platinum patients, the median DOR was slightly shorter, at 7 months. At the time of data cutoff, 64% (n = 9/14) of patients were still responding to treatment. Fifty-eight percent (n = 7/12) of post-platinum patients remained on the agent with a continued response.

With regard to safety, 96% of patients experienced adverse effects (AEs), although the majority of cases were determined to be grade 1 or 2 in severity. Dose reductions and discontinuations were reported to be infrequent. The most frequently reported all-grade toxicities comprised rash, infusion-related reaction, and paronychia. Infusion-related reactions mostly occurred at the time of the first infusion and was not serious enough to prevent subsequent doses. No grade 3 or higher rash was reported.

Serious AEs determined to be associated with amivantamab included cellulitis, interstitial lung disease, and shoulder or chest pain; these effects were reported in 6% (n = 3) of patients. Any toxicities that resulted in death were not determined to be related to the study drug.

Additional data from the trial were presented during the 2020 ESMO Virtual Congress and showed that amivantamab in combination with lazertinib resulted in high response rates with favorable tolerability in treatment-naïve and osimertinib (Tagrisso)-resistant patients with advanced EGFR-mutant NSCLC.3

Specifically, at a median follow-up of 7 months, the ORR and the CBR was 100% (95% CI, 83%-100%) in treatment-naïve patients; this comprised 20 PRs. At a median follow-up of 4 months, the ORR was 36% (95% CI, 22%-51%) in the osimertinib-resistant, chemotherapy-naïve patients; this was comprised of 1 complete response, 15 PRs, and 1 pending confirmation of PR. The CBR in this subset was 60% (95% CI, 44%-74%).

“Lung cancer remains the leading cause of cancer deaths worldwide. Given this significant unmet need, we at Johnson & Johnson are committed to improving outcomes for patients diagnosed with this complex, deadly disease. With today’s submission for amivantamab, we are one step closer to that goal,” Mathai Mammen, MD, PhD, global head of Janssen Research & Development at Johnson & Johnson, added in the release. “We are steadfast in our focus to advance novel therapeutics and medicines that will transform the trajectory of some of the most challenging and deadly diseases of our time, including lung cancer.


  1. Janssen submits application to US 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. The Janssen Pharmaceutical Companies of Johnson & Johnson. December 3, 2020. Accessed December 3, 2020. https://bwnews.pr/2JCpmVb.
  2. Park K, John T, Kim S-W, 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 15):9512. doi:10.1200/JCO.2020.38.15_suppl.9512
  3. Cho BC, Lee KH, Cho EK, et al. Amivantamab (JNJ-61186372), an EGFR-MET bispecific antibody, in combination with lazertinib, a 3rd-generation EGFR tyrosine kinase inhibitor, in advanced EGFR-mutant NSCLC. Ann Oncol. 2020;31(suppl 4):813. doi:10.1016/j.annonc.2020.08.1572
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