FDA Accepts sBLA for Amivantamab/Chemo in EGFR Exon 20+ NSCLC

The FDA previously granted accelerated approval to amivantamab as a treatment for adult patients with advanced or metastatic EGFR exon 20 insertion mutation–positive NSCLC that has progressed following platinum-based chemotherapy in 2021.

The FDA has received a supplemental biologics license application (sBLA) for the expanded approval of amivantamab-vmjw (Rybrevant) plus carboplatin/pemetrexed as a frontline treatment for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations, according to a press release from The Janssen Pharmaceutical Companies of Johnson & Johnson.¹

Supporting data for the sBLA came from the phase 3 PAPILLON trial (NCT04538664). According to a previous report, amivantamab in combination with chemotherapy produced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy on its own.² Additionally, investigators reported that the experimental regimen demonstrated a safety profile that was consistent with previous reports for each individual agent.

The FDA previously granted accelerated approval to amivantamab as a treatment for adult patients with advanced or metastatic EGFR exon 20 insertion mutation–positive NSCLC that has progressed following platinum-based chemotherapy in 2021.³ The accelerated approval was based on findings from the phase 1 CHRYSALIS study (NCT02609776), in which investigators assessed amivantamab monotherapy in patients previously treated with chemotherapy. The sBLA is intended to fulfill the FDA’s requirements for confirming the clinical benefits of amivantamab as observed in the CHRYSALIS study.

“[The] PAPILLON [study] is the first randomized phase 3 study in patients with NSCLC with EGFR exon 20 insertion mutations to show clinically meaningful results,” Kiran Patel, MD, vice president of Clinical Development in Solid Tumors at Janssen Research & Development, LLC, said in the press release.¹ “This creates an opportunity to make a significant improvement to the standard of care for this patient population with high unmet medical need. We look forward to working with the FDA through the [Real-Time Oncology Review] pathway in pursuit of an approval for [amivantamab] plus chemotherapy as we simultaneously progress the development of this novel bispecific antibody in additional patient populations.”

Investigators of the open-label, randomized PAPILLON trial are assessing the safety and efficacy of amivantamab plus chemotherapy vs chemotherapy alone in patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion–mutated NSCLC. In one of the experimental arms, patients received 1400 mg of amivantamab intravenously once a week up to day 1 of cycle 2 followed by 1750 mg of the agent on day 1 of each subsequent 21-day cycle.

The trial’s primary end point is PFS as assessed by blinded independent central review per RECIST v1.1 criteria. Secondary end points include objective response rate, duration of response, overall survival, time to subsequent therapy, safety, and quality of life.

Patients 18 years and older with measurable disease per RECIST v1.1 criteria and an ECOG performance status of 0 or 1 were able to enroll on the study.

References

1. Janssen submits supplemental biologics license application to the U.S. Food and Drug Administration seeking approval of RYBREVANT® (amivantamab-vmjw) in combination with chemotherapy for the first-line treatment of patients with locally advanced or metastatic EGFR exon 20 insertion mutation-positive non-small cell lung cancer. News release. Janssen Pharmaceuticals. August 25, 2023. Accessed August 25, 2023. https://shorturl.at/lAPU8
2. 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 August 25, 2023. https://bit.ly/3PWj7f7
3. 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 August 25, 2023. https://bit.ly/3PYEcFw