1506TiP - A single-arm, phase II study of amivantamab (AMI), lazertinib (L) and pemetrexed (P) for first-line treatment of recurrent/metastatic non-small cell lung cancers (NSCLCS) with epidermal growth factor receptor mutations in Exons 19 or 21 (EGFR 19/21): AMIGO 1 (LACOG0821)

Background

Osimertinib (osi) is the current first-line standard treatment for patients with NSCLCs with EGFR 19/21. Data suggest that combining EGFR tyrosine kinase inhibitor (TKI) with chemotherapy may be superior to a sequential approach of first-line TKI followed by salvage therapy. AMI is an EGFR/MET bi-specific antibody currently approved for NSCLCs with EGFR exon 20 insertions, but which is also being evaluated for NSCLCs with EGFR 19/21 in combination with chemotherapy (MARIPOSA-2 study) after osi progression. We designed AMIGO-1 to test the primary hypothesis that, in the first-line setting, the triplet regimen of AMI, combined with the 3rd generation irreversible TKI L, and P will improve progression-free survival (PFS) compared to historical controls, with an acceptable safety profile.

Trial design

AMIGO 1 is a single-arm, phase 2, multicenter trial, conducted through LACOG. Eligibility criteria include treatment-naïve, PS 0–1 patients with advanced NSCLCs with EGFR 19/21. Patients receive L 240mg PO daily, plus 21-day cycles of P 500mg/m² IV on Day 1, plus A: 1400mg IV (1750mg if body weight >=80Kg) once weekly in cycle 1; 1400mg IV (1750mg if body weight >=80Kg) on Day 1 in cycle 2; 1750mg IV (2100mg if body weight >=80Kg) at Day 1 from cycle 3 onwards. The primary endpoint is 18-month PFS (18m-PFS), estimated by the Kaplan-Meier method. A one group chi-square test with a type I error of 0.1 (one-sided) will have 80% power to detect the difference between the null hypothesis (18m-PFS of 50%, achieved with osi alone) and the alternative hypothesis (18m-PFS of 65%) with a sample size of 49. AMIGO-1 trial was opened to recruitment in May 2023 in research centers in Brazil. Clinical trial information: NCT05299125. This trial in progress is the first to assess the triplet regimen of lazertinib, amivantamab, and pemetrexed as first-line treatment for (NSCLCs) with EGFR mutations and will provide benchmark results to be contrasted with the present standard of care and future treatment combinations that are currently undergoing evaluation in phase 3 trials (eg. FLAURA2, MARIPOSA).

Clinical trial identification

NCT05299125.

Editorial acknowledgement

Legal entity responsible for the study

Latin American Cooperative Oncology Group (LACOG).

Funding

Janssen.

Disclosure

W. Nassib William Junior: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BMS, Eli Lilly, Merck, Roche/Genentech, Boehringer Ingelheim, Pfizer, Bayer, Sanofi, Takeda, Novartis, Libbs, Janssen. G. De Castro Jr.: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, TEVA; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Libbs, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, TEVA, Yuhan; Financial Interests, Local PI: Amgen, AstraZeneca, Bristol Myers Squibb, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Roche; Financial Interests, Steering Committee Member: AstraZeneca, Bayer, BeiGene, Merck Sharp & Dohme; Financial Interests, Personal, Steering Committee Member: GSK, Novartis; Financial Interests, Institutional, Local PI: Lilly, Pfizer, Sanofi. All other authors have declared no conflicts of interest.