Lirafugratinib Shows Broad Tumor Activity Beyond Initial Indications, Relay Therapeutics Shifts Strategic Focus

Relay Therapeutics revealed encouraging clinical outcomes for its lead candidate lirafugratinib (RLY-4008) across multiple FGFR2-altered malignancies, signaling a potential pivot toward wider tumor-agnostic applications rather than a narrower cancer focus.

Multi-Tumor Efficacy Emerges from Phase 1/2 ReFocus Trial

Data presented at the 2023 AACR-NCI-EORTC conference highlighted lirafugratinib’s therapeutic potential across diverse patient populations. The ongoing ReFocus trial enrolled 84 FGFR inhibitor-naive individuals across 18 different tumor types by late August 2023, with patients having received a median of three prior treatment regimens—demonstrating activity in heavily pretreated cohorts.

Among patients harboring FGFR2 fusion alterations, nine of 26 individuals achieved partial response status, translating to a 35% objective response rate spanning 11 distinct tumor categories including pancreatic, ovarian, and gastric malignancies. Notably, 63% of confirmed responders maintained therapeutic benefit for at least six months, suggesting durable clinical effect rather than transient response.

HR+/HER2- Breast Cancer Shows Particularly Strong Response Profile

The breast cancer population demonstrated especially compelling results. Of 10 evaluable patients with hormone receptor-positive, HER2-negative breast cancer, four achieved partial responses (40% response rate). Three of these four responders remained on active treatment at data cutoff, with one maintaining response for 72 weeks and ongoing. This cohort represented extremely heavily pretreated individuals, with a median of six prior therapies, including virtually universal prior endocrine therapy and CDK4/6 inhibitor exposure.

Activity Observed Across Amplification and Mutation Subgroups

The trial also documented lirafugratinib activity in patients with FGFR2 amplifications, where eight of 34 patients achieved partial responses (24% response rate) across gastric, breast, colorectal, and esophageal tumor types. Additionally, early signals emerged in the FGFR2 mutation population, with three of 24 patients demonstrating partial responses across breast, gastric, and ameloblastic histologies.

Strategic Recalibration: From Narrow to Broad Development Path

The company announced a notable strategic shift—pausing near-term commercial readiness efforts for cholangiocarcinoma to align with broader tumor-agnostic opportunities. This decision reflects confidence that lirafugratinib’s benefit extends well beyond the initially targeted indication, justifying a more expansive development strategy. Enrollment continues across the three tumor-agnostic cohorts, with additional clinical data and regulatory updates anticipated in 2024.

Safety Profile Remains Manageable

Adverse events remained consistent with previous safety disclosures. Most treatment-related toxicities were on-target FGFR-related effects—low-grade, monitorable, and largely reversible. Notably, no Grade 4 or 5 adverse events occurred, and off-target toxicities including hyperphosphatemia and diarrhea remained clinically insignificant.

Pipeline Prioritization and Extended Cash Runway

Concurrent with the strategic refocus, Relay Therapeutics announced plans to prioritize PI3Kα mutant-selective development. The company intends to initiate RLY-2608 triplet combination trials—pairing the candidate with fulvestrant and CDK4/6 inhibitors—by year-end 2023. The decision to pause CCA commercial readiness and discontinue RLY-2139 (CDK2 inhibitor) development extended the company’s cash runway into the second half of 2026, providing extended runway for its refined portfolio strategy.

These developments underscore Relay Therapeutics’ commitment to maximizing lirafugratinib’s clinical potential across the broader FGFR2-altered tumor landscape while strengthening complementary precision medicine programs.