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Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) as first-line (1L) treatment for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): First results of the CheckMate 8HW study.

2024; Lippincott Williams & Wilkins; Volume: 42; Issue: 3_suppl Linguagem: Inglês

10.1200/jco.2024.42.3_suppl.lba768

1527-7755

Thierry André, Elena Élez, Eric Van Cutsem, Lars Henrik Jensen, Jaafar Bennouna, Guillermo Méndez, Michael Schenker, Christelle de la Fouchardière, María Luisa Limón, Takayuki Yoshino, Jin Li, Heinz‐Josef Lenz, José Luis Manzano Mozo, Giampaolo Tortora, Rocio García‐Carbonero, Elvis Cela, Yingsi Yang, Ming Lei, Lixian Jin, Sara Lonardi,

Cancer Immunotherapy and Biomarkers

LBA768 Background: Patients (pts) with MSI-H/dMMR mCRC have poor outcomes with standard chemo ± targeted therapies. NIVO ± IPI are approved in previously treated pts with MSI-H/dMMR mCRC in many countries, based on the phase 2 CheckMate 142 study. CheckMate 8HW (NCT04008030) is a randomized phase 3 study comparing NIVO + IPI with NIVO or chemo in pts with MSI-H/dMMR mCRC. We report progression-free survival (PFS) by blinded independent central review (BICR) at a prespecified interim analysis for NIVO + IPI vs chemo in the 1L setting. Methods: Pts ≥ 18 years with recurrent or mCRC not amenable to surgery and MSI-H/dMMR status per local testing were enrolled across different lines of therapy. Previously untreated pts were randomized 2:2:1 to NIVO (240 mg) + IPI (1 mg/kg) Q3W (4 doses, then NIVO 480 mg Q4W), NIVO (240 mg) Q2W (6 doses, then NIVO 480 mg Q4W), or chemo ± targeted therapies; treatments continued until disease progression or unacceptable toxicity (all arms), or a maximum of 2 years (NIVO ± IPI arms). For pts with BICR-documented progression with chemo, optional crossover to NIVO + IPI was permitted. Dual primary endpoints were PFS by BICR per RECIST v1.1 for NIVO + IPI vs chemo (1L) and NIVO + IPI vs NIVO (all lines) in pts with centrally confirmed MSI-H/dMMR mCRC. Results: In the 1L setting, 303 pts were randomized to NIVO + IPI (n = 202) or chemo (n = 101); of these pts, 171 pts in the NIVO + IPI arm and 84 pts in the chemo arm had centrally confirmed MSI-H/dMMR result by either immunohistochemistry and/or polymerase chain reaction-based tests. With 24.3 months of median follow-up, NIVO + IPI demonstrated clinically meaningful and statistically significant improvement in PFS vs chemo, with a 79% reduction in the risk of disease progression or death (HR 0.21 [95% CI 0.14–0.32]; P < 0.0001) (Table). No new safety signals were identified (Table). Conclusions: NIVO + IPI demonstrated superior PFS vs chemo in previously untreated pts with MSI-H/dMMR mCRC. NIVO + IPI had a different safety profile compared to chemo, with fewer grade 3–4 treatment-related adverse events (TRAEs). These results support 1L NIVO + IPI as a standard-of-care option for pts with MSI-H/dMMR mCRC. Clinical trial information: NCT04008030 . [Table: see text]