Amivantamab Plus Chemotherapy Improves PFS in EGFR Exon 20–Mutant NSCLC

Amivantamab-vmjw (Rybrevant) plus carboplatin and pemetrexed led to a clinically meaningful and statistically significant improvement in progression-free survival (PFS) vs carboplatin and pemetrexed alone in patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion–mutated non–small cell lung cancer (NSCLC), meeting the primary end point of the phase 3 PAPILLON trial (NCT04538664). The safety profile of the combination was also comparable to that of each agent alone according to topline findings from the trial.¹

The data, which are the first to demonstrate clinically meaningful benefit in a randomized trial in this population, will be submitted for presentation at an upcoming scientific congress.

“The results from the PAPILLON study support the efficacy of amivantamab plus chemotherapy in the treatment of patients with NSCLC with [EGFR] exon 20 insertion mutations,” Peter Lebowitz, MD, PhD, Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC, stated in a news release. “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.”

In May 2021, the FDA granted accelerated approval to amivantamab for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.² Approval was based on findings from an 81-patient study, showing an overall response rate (ORR) of 40% and median duration of response of 11.1 months in this population.

PAPILLON was the confirmatory study needed for continued approval of the agent in this indication.¹

PAPILLON is a randomized, open-label, phase 3 study evaluating the efficacy and safety of amivantamab in combination with chemotherapy compared with chemotherapy alone in patients with treatment-naïve advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations.

To be eligible for enrollment, patients must have histologically or cytologically confirmed locally advanced or metastatic nonsquamous NSCLC with documented primary EGFR exon 20 insertion activating mutation; have measurable disease per RECIST v1.1 criteria; have an ECOG performance status of 0 or 1; and agree to undergo pretreatment tumor biopsy and provide baseline and longitudinal blood samples.³

Amivantamab is being administered by intravenous infusion at a dose 1400 mg (1750 mg if body weight ≥80 kg) once a week up to cycle 2 day 1, then 1750 mg (2100 mg if body weight ≥80 kg) on day 1 of each 21-day cycle thereafter.

In both arms, patients are receiving 500 mg/m² of pemetrexed on day 1 of each 21-day cycle, plus up to 4 cycles of carboplatin at an area under the concentration-time curve of 5 mg/mL per minute on day 1 of each 21-day cycle. Pemetrexed is continuing as maintenance therapy until disease progression.

The primary end point of the study is PFS according to RECIST v1.1 criteria assessed by blinded independent central review. Secondary end points include ORR, PFS after first subsequent therapy, time to symptomatic progression, and overall survival.

Notably, patients assigned to chemotherapy alone are allowed to receive amivantamab in the second-line setting after confirmed disease progression.

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. The Janssen Pharmaceutical Companies of Johnson & Johnson. July 17, 2023. Accessed July 17, 2023. https://www.prnewswire.com/news-releases
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. The Janssen Pharmaceutical Companies of Johnson & Johnson. May 21, 2021. Accessed July 17, 2023. https://www.jnj.com/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
3. A study of combination amivantamab and carboplatin-pemetrexed therapy, compared with carboplatin-pemetrexed, in participants with advanced or metastatic non-small cell lung cancer characterized by epidermal growth factor receptor (EGFR) exon 20 insertions (PAPILLON). ClinicalTrials.gov. Updated June 29, 2023. Accessed July 17, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04538664