Amivantamab, lazertinib and bevacizumab gave a 33% response rate after osimertinib in AMAZE-lung

A chemotherapy-free alternative to the MARIPOSA-2 regimen

Amivantamab, a bispecific antibody against EGFR and MET, is approved with chemotherapy for EGFR-mutant NSCLC after progression on osimertinib, on the basis of the MARIPOSA-2 trial. AMAZE-lung tested whether chemotherapy could be replaced with lazertinib, a third-generation EGFR TKI, and bevacizumab, an anti-VEGF antibody. The authors’ rationale is that MET and angiogenic pathways become activated in EGFR-mutant NSCLC as resistance to TKIs develops.

Eligible adults had a sensitising EGFR mutation and had progressed on osimertinib or lazertinib given in the first or second line. Amivantamab was dosed at 1400 mg (1750 mg at 80 kg or more) for the first two cycles, then at 1750 mg (2100 mg at 80 kg or more) from cycle three. Treatment continued until progression or intolerable toxicity. The trial was run by the European Thoracic Oncology Platform (ETOP) and funded by the ETOP IBCSG Partners Foundation and Janssen Pharmaceutica.

Twenty responses at 12 weeks, one more than the threshold required

The statistical design required at least 19 responses among the first 60 patients to reject a response rate of 20% or less in favour of 40%, at a 2.2% significance level with 93% power. Twenty patients responded by week 12, which met the primary endpoint with one response to spare.

Over the full cohort of 61 patients, 24 (39%; 95% CI 27 to 53) had a partial response, and 22 of these were confirmed at a subsequent tumour evaluation. The point estimate of 33% sits below the 40% rate the design was powered to detect, and the 95.6% confidence interval runs from 21% to 47%.

The patients enrolled were mostly women (70%), White (82%) and never-smokers (61%), with a median age of 65 years. Sixty-two per cent had an ECOG performance status of 1 and 61% had stage IVB disease. All tumours were adenocarcinomas.

“Combined amivantamab, lazertinib, and bevacizumab showed durable anti-tumour activity, representing a promising chemotherapy-sparing alternative after progression on third-generation EGFR TKIs.”Soo et al., The Lancet Respiratory Medicine (2026)

Infusion reactions in 58% and venous thromboembolism in 17%

Safety was assessed in the 60 patients who received at least one dose. Infusion-related reactions of any grade occurred in 35 patients (58%) and acneiform rash in 30 (50%). Treatment-related venous thromboembolism was reported in ten patients (17%), two of them (3%) at grade 3 to 4.

Serious treatment-related adverse events occurred in 12 patients (20%). The authors describe the safety findings as consistent with known toxicity profiles.

A single-arm result with nine months of follow-up

AMAZE-lung had no comparator arm, so the response rate cannot be set directly against amivantamab plus chemotherapy or against chemotherapy alone in the post-osimertinib setting. At the database cutoff of 26 August 2024, median follow-up was 9.0 months (IQR 5.8 to 12.6), and 28 patients were still receiving the combination. Follow-up for these patients is ongoing.