Cullinan Therapeutics begins FDA submission for zipalertinib combination
The first-line application is expected to be completed by year end; a separate monotherapy NDA has a Feb. 27, 2027 FDA target.
Adrian Kessler
A first-line lung cancer NDA submission began Thursday as Cullinan Therapeutics, Inc. NASDAQCGEM initiated its zipalertinib combination filing under FDA's real-time review program; shares closed at US$14.53, down 5.34 per cent, at 4 p.m. EDT on Oct. 1.
The Oct. 1 SEC filing says Cullinan expects to complete the first-line application by year-end 2026. In a Phase 3 trial reported Sept. 13, the combination extended median progression-free survival to 14.5 months from 8.5 months with chemotherapy alone.
Cullinan is a Cambridge, Massachusetts clinical-stage drug developer working on treatments for cancer and autoimmune disease. Zipalertinib is an investigational oral drug designed to target a particular EGFR mutation in non-small cell lung cancer.
The quote page had no Oct. 2 regular-session price when checked, so the day's trading response was still unavailable.
REZILIENT3 Shows Progression Benefit and More Severe Events
That REZILIENT3 report said 279 patients were randomized after a six-person safety lead-in. Of those randomized, 140 received zipalertinib plus chemotherapy and 139 received chemotherapy alone. All had previously untreated advanced non-small cell lung cancer with EGFR exon 20 insertion mutations.
Median progression-free survival, the trial's primary endpoint, was 14.5 months for the combination and 8.5 months for chemotherapy. The hazard ratio was 0.50, with a 95 per cent confidence interval of 0.34 to 0.73. The company reported a P value of 0.00015.
Grade 3 or higher adverse events occurred in 87.1 per cent of combination patients against 54.4 per cent on chemotherapy, mainly blood-related events. Overall survival data were immature at the interim analysis, with 30 per cent of events recorded; the reported confidence interval still included no difference in survival.
FDA Review Has Two Separate Timetables
The FDA says its RTOR program lets companies submit topline efficacy and safety results before a complete oncology application, giving reviewers an earlier start. Cullinan's filing says it initiated that process after agreement with the agency; it does not say the FDA has approved zipalertinib for any use.
"Acceptance into the RTOR program does not guarantee or influence approvability of the application, which is subject to the same statutory and regulatory requirements for approval as applications that are not included in RTOR," the FDA says on its program page.
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A separate zipalertinib monotherapy NDA seeks accelerated approval for patients already treated with platinum-based chemotherapy. Its FDA target action date is Feb. 27, 2027, according to Cullinan's Oct. 1 filing. That date does not apply to the first-line combination application.
That filing says Cullinan could receive up to US$100 million from Taiho if the combination wins U.S. first-line approval. A separate US$30 million payment depends on U.S. approval in previously treated patients. The Oct. 1 filing did not update Cullinan's cash balance or runway.
Johnson & Johnson NYSEJNJ already has FDA approval for Rybrevant plus chemotherapy in first-line EGFR exon 20 insertion lung cancer. Its March 1, 2024 release says PAPILLON showed a 61 per cent lower risk of progression or death against chemotherapy alone. Those results come from a different trial and cannot directly rank the two combinations.
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Cullinan expects to complete its first-line combination NDA by year-end 2026, the next stated submission milestone. The separate monotherapy application has an FDA PDUFA target action date of Feb. 27, 2027.
