FDA Accepts sBLA for Amivantamab/Chemo in EGFR+ Advanced/Metastatic NSCLC

“The promising results from the MARIPOSA-2 study show that by combining [amivantamab] with chemotherapy, both with and without lazertinib, patients achieved longer [PFS] compared with chemotherapy alone,” according to Antonio Passaro, MD, PhD.

Developers have submitted a supplemental biologics license application (BLA) to the FDA for the potential approval of amivantamab-vmjw (Rybrevant) plus carboplatin and pemetrexed for locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or L858R substitutions following disease progression with osimertinib (Tagrisso), according to a news release from The Janssen Pharmaceutical Companies of Johnson & Johnson.¹

“New treatment options are urgently needed in the post-osimertinib setting, where patients continue to face unacceptable survival rates,” Kiran Patel, MD, vice president of Clinical Development, Solid Tumors, at Janssen Research & Development, LLC, said in the news release. “As we strive to transform the standard of care in patients with EGFR-mutated NSCLC, we are committed to working closely with the FDA during review of this submission for [amivantamab] in this expanded patient population.”

Supporting data for the supplemental BLA came from the phase 3 MARIPOSA-2 study (NCT04988295), which investigators presented at the 2023 European Society for Medical Oncology (ESMO) Congress and subsequently published in Annals of Oncology.

Investigators reported a median progression-free survival (PFS) of 8.3 months (95% CI, 6.8-9.1) among those who received amivantamab plus lazertinib (Leclaza) and chemotherapy (n = 263), 6.3 months (95% CI, 5.6-8.4) in those treated with amivantamab and chemotherapy (n = 131), and 4.2 months (95% CI, 4.0-4.4) in patients who received chemotherapy alone (n = 263).²

Grade 3 or higher adverse effects affected 72% of patients in the amivantamab plus chemotherapy arm, 92% of those who received amivantamab plus lazertinib and chemotherapy, and 48% of those treated with chemotherapy alone. The most common high-grade toxicities included neutropenia, thrombocytopenia, anemia, and leukopenia. Febrile neutropenia was reported in 2%, 8%, and 2% of patients in each respective arm.

“The promising results from the MARIPOSA-2 study show that by combining [amivantamab] with chemotherapy, both with and without lazertinib, patients achieved longer [PFS] compared with chemotherapy alone,” lead study author Antonio Passaro, MD, PhD, medical oncologist in the Division of Thoracic Oncology at the European Institute of Oncology in Milan, Italy, said in a press release on these findings.³ “The efficacy seen across the two [amivantamab] regimens suggests that this treatment combination may address the diverse and often varied resistance that can occur in the post-osimertinib setting.”

Patients included in the MARIPOSA-2 trial were randomly assigned 2:2:1 to receive amivantamab plus lazertinib and chemotherapy, chemotherapy alone, or amivantamab plus chemotherapy every 3 weeks.² Investigators administered amivantamab intravenously at 1400 mg weekly for 4 weeks followed by 1750 mg every 3 weeks beginning with the third cycle. Chemotherapy consisted of pemetrexed at 500 mg/m² every cycle plus carboplatin at area under the curve 5 for the first 4 cycles.

The trial’s dual primary end points were PFS with amivantamab-chemotherapy and amivantamab-lazertinib-chemotherapy compared with chemotherapy alone. Secondary end points included objective response rate, duration of response, overall survival, symptomatic and intracranial PFS, and safety.

Patients 18 years and older with locally advanced or metastatic NSCLC harboring EGFR mutations that progressed on or after therapy with osimertinib were able to enroll on the trial. Those with brain metastases were able to enroll if their condition was clinically stable, asymptomatic, and treated with stable steroid doses.

References

1. Janssen submits supplemental biologics license application to U.S. FDA seeking approval of RYBREVANT® (amivantamab-vmjw) plus chemotherapy for the treatment of patients with EGFR-mutated non-small cell lung cancer who progressed on or after osimertinib. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. November 20, 2023. Accessed November 20, 2023. https://shorturl.at/cnzBP
2. Passaro A, Wang J, Wang Y, et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. Published online October 23, 2023. doi:10.1016/j.annonc.2023.10.117
3. Phase 3 MARIPOSA-2 study shows RYBREVANT® (amivantamab-vmjw) plus chemotherapy given with or without lazertinib reduced risk of disease progression or death by 56 and 52 percent respectively in patients with EGFR-mutated non-small cell lung cancer who progressed on or after osimertinib. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. October 23, 2023. Accessed November 20, 2023. https://shorturl.at/efgwQ