January 4th, 2021 - A marketing authorization application has been submitted to the European Medicines Agency for the approval of amivantamab as a treatment for patients with metastatic non–small cell lung cancer that harbors EGFR exon 20 insertion mutations who have experienced disease progression following platinum-based chemotherapy.
A marketing authorization application has been submitted to the European Medicines Agency (EMA) for the approval of amivantamab (JNJ-61186372; JNJ-6372) as a treatment for patients with metastatic non–small cell lung cancer (NSCLC) that harbors EGFR exon 20 insertion mutations who have experienced disease progression following platinum-based chemotherapy.1
The application was based on findings from the monotherapy arm of the phase 1 CHRYSALIS trial (NCT02609776), in which amivantamab induced an overall response rate (ORR) of 36% (95% CI, 21%-53%) in the 39 patients who were determined to be evaluable for response.2 Moreover, the partial response (PR) with the agent was 36% (95% CI, 21%-53%).
Notably, in the 29 patients who had prior platinum-based chemotherapy, the ORR was 41% with amivantamab (95% CI, 24%-61%). The clinical benefit rate achieved with amivantamab was 67% in response-evaluable participants and 72% for the subset of patients who had previously received platinum-based chemotherapy.
Additionally, of the 14 patients who responded to treatment, the median duration of response (DOR) was reported to be 10 months (range, 1-16). In patients who had received prior platinum-based chemotherapy, the median DOR was slightly shorter, at 7 months (range, 1-16). Sixty-four percent of patients (n = 9/14) continued to respond to treatment at the time of data cutoff; this was true for 58% (n = 7/12) of patients who had prior platinum-based chemotherapy.
“The EMA submission represents an important milestone in our commitment to develop innovative, targeted therapies like amivantamab for patients facing a lung cancer diagnosis,” Peter Lebowitz, MD, PhD, global therapeutic area head of Oncology at Janssen Research & Development, LLC, stated in a press release. “This is an important step forward in our drive toward improving outcomes for patients diagnosed with NSCLC who have EGFR exon 20 insertion mutations where there are no EMA-approved targeted treatments today.”
In the ongoing, 2-part, phase 1 trial, investigators evaluated amivantamab in patients with advanced NSCLC. In the first portion of the trial, investigators sought to establish the recommended phase 2 dose (RP2D) of the agent, while in the second portion, they evaluated the safety and preliminary efficacy of the drug, along with pharmacokinetics and immunogenicity.
To be eligible for enrollment, patients had to have metastatic or unresectable NSCLC, have experienced disease progression on previous therapy or have been ineligible for or refused current treatment options, and have had an ECOG performance status of 0-1.
Patients had to have evaluable disease for the first portion and measurable disease for the second portion of the research. Moreover, for part 2, patients had to have activating EGFR or MET mutations or amplifications and have progressed on prior standard-of-care therapy. Notably, patients with previously definitively treated brain metastases were permitted for inclusion.
For the dose-escalation portion of the trial, investigators evaluated amivantamab at doses starting at 140 mg, to 350 mg, 700 mg, 1050 mg, 1400 mg, up to 1750 mg. Investigators established the RP2D to be 1050 mg, administered intravenously once weekly for the first cycle and then biweekly thereafter. For patients who weighed 80 kg or more, the RP2D was higher, at 1400 mg.
Across both parts of the trial, a total of 50 participants with EGFR exon 20 insertion–mutated NSCLC were administered at least 1 dose of the agent at the recommended schedule. Of these patients, 39 were determined to be evaluable for response and a total of 13 EGFR exon 20 insertion mutations were observed.
Of the evaluable patients, 74% (n = 29) had previously received platinum-based chemotherapy in the metastatic setting, 6 were treatment naïve, and 4 had previously received other treatments like EGFR TKIs and/or a VEGF inhibitor.
Additional results presented during the 2020 ASCO Virtual Scientific Program showed reductions in target lesions in both the subgroup of patients who had prior platinum-based chemotherapy and in those who were treatment naïve. Notably, activity with the agent was reported across all of the distinct alterations identified.
Moreover, the median progression-free survival (PFS) was 8.3 months (95% CI, 3.0-14.8) in the total patient population, with substantial early censoring. The median PFS was slightly longer, at 8.6 months (95% CI, 3.7-14.8) in those who had prior platinum-based chemotherapy.
With regard to safety, 96% of participants experienced toxicities, although the majority (60%) of these effects were either grade 1 or 2 in severity. The most frequently reported all-grade adverse effects (AEs) included rash, infusion-related reaction (IRR), and paronychia. In most cases, IRR was experienced on the first infusion of the agent and was not found to prevent subsequent treatments. Notably, no grade 3 or higher rash was experienced, although 1 patient reported grade 3 diarrhea.
Additionally, 6% of patients experienced treatment-related AEs that were grade 3 or higher in severity; these included hyperamylasemia, hypokalemia, increased lipase, and shoulder/chest pain. Serious toxicities associated with the treatment were reported in 6% (n = 3) of patients and included cellulitis, interstitial lung disease, and shoulder/chest pain.
Ten percent (n = 5) of patients required dose reductions and 6% (n = 3) discontinued treatment. No consistent pattern of severe toxicity was linked with dose interruption or modification.
“Lung cancer is the biggest cause of cancer death in Europe and has 1 of the lowest 5-year survival rates for patients with cancer. Given this significant unmet need, we are committed to improving outcomes for patients diagnosed with this complex disease,” Mathai Mammen, MD, PhD, global head of Janssen Research & Development of Johnson & Johnson, added in the release. “With today’s submission for amivantamab, we are one step closer to our goal of advancing novel therapeutics that will transform the trajectory of some of the most challenging diseases of our time, including lung cancer.”
Earlier in December 2020, a biologics license application was submitted to the FDA for amivantamab for use in patients with metastatic NSCLC with EGFR exon 20 insertion mutations who have progressed on or after a platinum-based chemotherapy. The application was based on data from CHRYSALIS.