Ongoing Trials Investigate Amivantamab Combinations for EGFR+ NSCLC

Melina E. Marmarelis, MD, medical director of Penn Medicine Mesothelioma and Pleural Program and assistant professor of medicine at the Hospital of the University of Pennsylvania, reports the study design of the Chrysalis-2 trial (NCT04077463) and ongoing trials researching the combination of amivantamab (Rybrevant) and lazertinib (Leclaza) in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC).

There was a cohort of 20 patients in the phase 2 Chrysalis-2 trial, 14 of whom had previously received osimertinib (Tagrisso) and 6 of whom had received a first- or second-generation EGFR tyrosine kinase inhibitor for EGFR-positive NSCLC. The primary end point was safety, and clinical benefit rate was a secondary end point.

Patients received lazertinib and amivantamab weekly for 4 weeks, then every 3 weeks with carboplatin and pemetrexed (Alimta). Carboplatin was discontinued after 4 cycles whereas pemetrexed was given as maintenance. This cohort whose data were presented at the 2022 World Conference on Lung Cancer showed a high clinical benefit rate in addition to a tolerable safety profile.

Marmarelis says that though this cohort focused on safety, ongoing studies are investigating the efficacy of this combination. The MARIPOSA-2 trial (NCT04988295) is investigating this regimen in patients post osimertinib, and the PAPILLON study (NCT04538664) is evaluating it as frontline therapy for patients with EGFR exon 20 alterations.

TRANSCRIPTION:

0:08 | This [cohort of the Chrysalis-2 study] was a small cohort of 20 patients looking primarily at safety. Safety was the primary end point. There were secondary end points that were based on efficacy such as clinical benefit rate, which was defined as complete response, partial response, or stable disease for 11 weeks or greater based on RECIST 1.1.

The patients were given lazertinib daily, amivantamab weekly for the first 4 weeks and then every 3 weeks with chemotherapy. The chemotherapy agents were carboplatin and pemetrexed given every 3 weeks and carboplatin was given for a total of 4 cycles while pemetrexed was continued through maintenance. Patients were evaluated for safety and for efficacy. The results were presented at [the 2022 World Conference on Lung Cancer].

0:57 | The primary goal of this cohort that was presented was to look at the safety. There are several ongoing studies that are looking at this combination in different settings. MARIPOSA-2 is looking at the combination of amivantamab, lazertinib, and chemotherapy in post osimertinib settings. The PAPILLON study is looking at this combination in frontline [patients with] EGFR exon 20 NSCLC. We look forward to those results.