Confirmatory Amivantamab NSCLC Trial Demonstrates Meaningful Benefit

The randomized, open-label phase 3 PAPILLON trial was created to evaluate the effectiveness and toxicity profile of amivantamab and chemotherapy vs chemotherapy alone in a population with newly diagnosed, advanced/metastatic, EGFR exon 20–mutant NSCLC.

Treatment with amivantamab-vmjw (Rybrevant) plus chemotherapy yielded a clinically meaningful survival benefit over standard of care in patients with newly diagnosed, advanced or metastatic EGFR exon 20 insertion mutation–positive non–small cell lung cancer (NSCLC), according to confirmatory findings from the phase 3 PAPILLON trial (NCT04538664).¹

The study met its primary end point after investigators reported a clinically meaningful progression-free survival (PFS) benefit with the combination compared with chemotherapy. The safety of the regimen was also determined to be similar to toxicities observed with each individual agent.

“The results from the PAPILLON study support the efficacy of [amivantamab] plus chemotherapy in the treatment of patients with [NSCLC] with exon 20 insertion mutations,” Peter Lebowitz, MD, PhD, global therapeutic area head of Oncology at Janssen Research & Development. “[Amivantamab] was the first therapy approved in the relapsed/refractory setting for patients with EGFR exon 20 insertion mutations, a population that continues to experience persistent unmet medical needs. This phase 3 study is the first of several ongoing pivotal programs to read out evaluating [amivantamab]-based regimens in patients with EGFR-mutated [NSCLC].”

The randomized, open-label phase 3 PAPILLON trial was created to evaluate the effectiveness and toxicity profile of amivantamab and chemotherapy vs chemotherapy alone in a population with newly diagnosed, advanced/metastatic, EGFR exon 20–mutant NSCLC.

Patients were treated with a 1400 mg intravenous dose of amivantamab once a week up to cycle 2 day 1, wherein patients would receive 1750 mg on day 1 of every 21-day cycle beginning with cycle 3. Patients in both arms received 500 mg/m2 of intravenous pemetrexed on day 1 of every 21-day cycle along with carboplatin as an area under the curve 5 intravenous infusion for up to 4 cycles on day 1 followed by maintenance pemetrexed until disease progression.

The study’s primary outcome measure was PFS, with key secondary outcomes including objective response rate, duration of response, overall survival, time to subsequent therapy, PFS after subsequent therapy (PFS2), and time to symptomatic progression.

To enroll on the trial, patients were required to have histologically or cytologically confirmed locally advanced or metastatic nonsquamous disease and document EGFR exon 20 mutations. Patients also needed to have measurable disease by RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and agree to genetic characterization of tumor status via pretreatment tumor biopsy.

Results from the trial follow the FDA approval of amivantamab for EGFR exon 20 insertion mutant locally advanced/metastatic following progression during or following platinum-based chemotherapy in May of 2021.²

“Today’s FDA approval is an important development for people living with [NSCLC] with exon 20 insertion mutations who, until now, have had no approved treatment options to target their disease,” Jill Feldman, co-founder, and lung cancer patient advocate at EGFR Resisters, said in a press release at the time of the approval. “We are excited by the promise this new treatment option brings to people with this particular type of lung cancer and their families.”

References

1. Treatment with RYBREVANT® (amivantamab-vmjw) plus chemotherapy resulted in statistically significant and clinically meaningful improvement in progression-free survival in patients with newly diagnosed EGFR exon 20 insertion mutation-positive non-small cell lung cancer. News release. Janssen Pharmaceuticals. July 17, 2023. Accessed July 17, 2023. https://bit.ly/3PWj7f7
2. RYBREVANTTM (amivantamab-vmjw) receives FDA approval as the first targeted treatment for patients with non-small cell lung cancer with EGFR exon 20 insertion mutations. News release. Janssen Pharmaceuticals. May 21, 2021. Accessed July 17, 2023. https://bit.ly/3PYEcFw