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A new phase 3 trial is testing whether adding a LAG-3 blocker to standard chemoimmunotherapy can outperform pembrolizumab-based treatment in a hard-to-treat lung cancer population. The RELATIVITY-1093 trial targets patients with nonsquamous NSCLC and low-to-moderate PD-L1 expression — a group that often loses responses quickly. Early phase 2 data showed promising response rates and a manageable safety profile, setting the stage for this ~1,000-patient study.
The phase 3 RELATIVITY-1093 trial is putting a dual checkpoint strategy to the test in frontline nonsquamous non-small cell lung cancer (NSCLC). The trial compares a fixed-dose combination of nivolumab plus relatlimab (a LAG-3–blocking antibody) and platinum-pemetrexed chemotherapy against the current standard — pembrolizumab plus the same chemotherapy — in roughly 1,000 patients with PD-L1 expression of at least 1%. The core idea: PD-1 blockade alone doesn't fully reverse T-cell exhaustion, and targeting a second checkpoint (LAG-3) could reinvigorate the immune response more effectively.
The trial's primary focus is patients with PD-L1 expression of 1%–49% — a group that responds inconsistently to current immunotherapy and represents a significant unmet need. High PD-L1 expressors (≥50%) already have effective single-agent options, while this middle group often progresses within 18 months on standard therapy.
By the Numbers:
Why it matters: If RELATIVITY-1093 delivers a clinically meaningful OS improvement with durable responses and acceptable toxicity, it could redefine first-line treatment for a large subset of lung cancer patients who currently have limited options — and shift how oncologists think about tackling immunotherapy resistance from day one.
