FDA Approves First-Line Amivantamab Plus Lazertinib for EGFR+ Advanced NSCLC

FDA

The FDA has approved amivantamab-vmjw (Rybrevant) in combination with lazertinib (Lazcluze) for the first-line treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations, as detected by an FDA-approved test.¹

The regulatory decision was supported by data from the phase 3 MARIPOSA trial (NCT04487080) which showed that amivantamab plus lazertinib reduced the risk of progression or death by 30 percent compared with osimertinib (Tagrisso; HR, 0.70; 95% CI, 0.58-0.85; P < .001). Patients treated with the combination (n = 429) experienced a median progression-free survival (PFS) of 23.7 months compared with 16.6 months for those treated with osimertinib (n = 429).²

The objective response rate (ORR) was 86% (95% CI, 83%-89%) in the amivantamab/lazertinib arm vs 85% (95% CI, 81%-88%) in the osimertinib arm. The median duration of response (DOR) was 25.8 months (95% CI, 20.1–not estimable [NE]) in the experimental arm vs 16.8 months (95% CI, 14.8-18.5) in the control arm.²

"This approval is a crucial development for patients with EGFR-mutated NSCLC, who have faced significant unmet needs for far too long," Jill Feldman, lung cancer survivor and co-founder of the EGFR Resisters, a patient advocacy group, stated in a news release.¹ "Having witnessed firsthand the remarkable evolution in lung cancer treatment, this profoundly important milestone brings a novel therapeutic approach to patients and their families. I'm thrilled that more patients can now experience the PFS benefits seen in the MARIPOSA study."

MARIPOSA was an international, randomized trial that enrolled patients at least 18 years of age with previously untreated locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations. Patients were permitted to have asymptomatic or stable brain metastases.²

Patients were randomly assigned 2:2:1 to receive amivantamab plus lazertinib, osimertinib monotherapy, or lazertinib monotherapy. Amivantamab was given at 1050 mg (or 1400 mg in those with a body weight of at least 80 kg) once per week for the first 4 weeks, which included a split of the first infusion over 2 days (350 mg on cycle 1, day 1, and the remainder given on cycle 1, day 2). In cycle 2 and beyond, amivantamab was given once every 2 weeks. Osimertinib at 80 mg and lazertinib at 240 mg given once per day.

Blinded independent central review–assessed PFS per RECIST 1.1 criteria for the combination arm vs the osimertinib arm served as the trial's primary end point. Secondary end points included overall survival (OS), ORR, DOR, and safety.

The median OS was NE in both the amivantamab/lazertinib and osimertinib arms (HR, 0.80; 95% CI, 0.61-1.05). The 18- and 24-month OS rates in the experimental arm were 82% (95% CI, 78%-85%) and 74% (95% CI, 69%-78%), respectively. In the osimertinib arm, those respective rates were 79% (95% CI, 75%-83%) and 69% (95% CI, 64%-74%).

Regarding safety, the most common adverse effects reported in at least 20% of patients treated with amivantamab/lazertinib were rash, nail toxicity, infusion-related reactions with amivantamab, musculoskeletal pain, edema, stomatitis, venous thromboembolism, paresthesia, fatigue, diarrhea, constipation, COVID-19 infection, hemorrhage, dry skin, decreased appetite, pruritus, nausea, and ocular toxicity.³

Venous thromboembolic events were observed with lazertinib plus amivantamab, and the FDA recommended the use of prophylactic anticoagulation for the first 4 months of therapy.

The recommended dose for lazertinib is 240 mg once per day in combination with amivantamab with or without food. The recommended amivantamab dose is based on baseline body weight.

References

1. Rybrevant (amivantamab-vmjw) plus Lazcluze (lazertinib) approved in the U.S. as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer. News release. Johnson & Johnson. August 20, 2024. Accessed August 20, 2024. https://www.investor.jnj.com/news/news-details/2024/RYBREVANT-amivantamab-vmjw-plus-LAZCLUZE-lazertinib-approved-in-the-U.S.-as-a-first-line-chemotherapy-free-treatment-for-patients-with-EGFR-mutated-advanced-lung-cancer/default.aspx
2. Cho BC, Lu S, Felip E, et al. Amivantamab plus lazertinib in previously untreated EGFR-mutated advanced NSCLC. N Engl J Med. Published online June 26, 2024. doi:10.1056/NEJMoa2403614
3. FDA approves lazertinib with amivantamab-vmjw for non-small lung cancer. FDA. August 19, 2024. Accessed August 20, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lazertinib-amivantamab-vmjw-non-small-lung-cancer