Cullinan Therapeutics Reports Positive Phase 3 REZILIENT3 Results

What Happened

• On September 13, 2026 (8-K filed Sept. 14, 2026), Cullinan Therapeutics and partners Taiho Oncology/Taiho Pharmaceutical announced topline results from the Phase 3 REZILIENT3 trial testing zipalertinib plus platinum-based chemotherapy versus chemotherapy alone in first-line EGFR exon 20 insertion (ex20ins) non–small cell lung cancer (NSCLC).
• After a safety lead-in (n=6), 279 previously untreated advanced NSCLC patients with EGFR ex20ins were randomized (zipalertinib combo n=140; chemotherapy alone n=139). At the pre-planned interim PFS analysis (122 events), median progression-free survival was 14.5 months with zipalertinib+chemo vs. 8.5 months with chemo alone (hazard ratio 0.50; 95% CI 0.34–0.73; P=0.00015). Objective response rate was 65.0% vs. 40.3% (P<0.0001); median duration of response 14.2 vs. 9.9 months. Interim overall survival hazard ratio was 0.72 (95% CI 0.42–1.23) at ~30% maturity. No new safety signals were reported.

Key Details

• Trial: Phase 3 REZILIENT3; randomized n=279 after safety lead-in (6).
• Primary interim PFS: 14.5 months (zipalertinib combo) vs. 8.5 months (chemo); HR 0.50; P=0.00015.
• Response: ORR 65.0% vs. 40.3% (P<0.0001); median DOR 14.2 vs. 9.9 months.
• Safety: Grade ≥3 adverse events 87.1% (combo) vs. 54.4% (chemo); primarily hematologic (grade ≥3 hematologic 58.6% vs. 28.7%). Grade ≥3 EGFR-related rash 10.7% and diarrhea 1.4% (combo arm).

Why It Matters

• These positive Phase 3 topline results show a substantial improvement in progression-free survival and objective response rate for zipalertinib when added to chemotherapy in first-line EGFR ex20ins NSCLC, a patient population with limited targeted options.
• For investors, the data are material because they may affect regulatory strategy, timelines, commercial potential in a rare oncology indication, and partner (Taiho) collaboration plans. Continued follow-up is needed to confirm overall survival benefit and fully characterize safety and exploratory endpoints.