Cullinan and Taiho drug extends lung cancer
In a phase 3 trial, adding zipalertinib to chemotherapy improved median progression-free survival to 14.5 months, a six-month gain over chemo alone, for
Cullinan Therapeutics and Taiho Oncology have reported that their drug zipalertinib, combined with chemotherapy, extended median survival by six months for patients with a specific form of advanced lung cancer. The detailed results from the phase 3 Rezilient3 trial were presented at the World Conference on Lung Cancer in Seoul.
In the study of 279 previously untreated adults, the combination therapy achieved a median progression-free survival of 14.5 months. Patients receiving only chemotherapy had a median progression-free survival of 8.5 months. The objective response rate was also higher with the combination.
| Metric | Zipalertinib + Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Median Progression-Free Survival | 14.5 months | 8.5 months |
| Objective Response Rate | 65% | 40.3% |
| Median Duration of Response | 14.2 months | 9.9 months |
A Major Advance for Patients
Cullinan's Chief Medical Officer Jeffrey Jones described the data as a "major advance" for this patient population. "This is potentially practice-changing in extending progression-free survival beyond a year with an adverse event profile that is manageable," Jones told Fierce Biotech. The trial met its primary endpoint last month.
Overall survival data remains immature but shows promise. The hazard ratio for death was 0.72 for the zipalertinib regimen versus control, indicating a 28% lower risk of dying. Jones said these initial results should be viewed as encouraging.
Managing Treatment Side Effects
While adverse events were more common with the combination therapy, the companies stated they were primarily manageable. Most side effects leading to treatment discontinuation were attributed to the platinum chemotherapy, typically occurring in the first four months.
| Adverse Event Detail | Zipalertinib + Chemotherapy | Chemotherapy Alone |
|---|---|---|
| Grade 3 or Above Adverse Events | 87.1% | 54.4% |
| Most Common EGFR-Related Event (Rash, Grade 3+) | 10.7% | Not specified |
The partners noted that EGFR-related adverse events graded 3 or above were infrequent.
Targeting a Specific Mutation
The trial focused on non-small cell lung cancer patients with epidermal growth factor receptor exon 20 insertion mutations. Jones explained that EGFR mutations occur in nearly one third of NSCLC patients, with about 4% involving this specific exon 20 insertion in advanced disease. Zipalertinib is an oral drug designed to irreversibly inhibit these mutations by binding directly to exon 20.
A Competitive Treatment Landscape
The market for treating this mutation has been competitive. Johnson & Johnson's Rybrevant was approved as a first-line treatment in 2024. Although no head-to-head comparison exists, zipalertinib's reported median progression-free survival of 14.5 months compares to the 11.4-month figure for Rybrevant's approval. Takeda withdrew its drug Exkivity from the U.S. Market in 2023 after a confirmatory study failure.
Taiho plans to share the new data with global regulators, including the FDA, to seek a quick path to market. The FDA is already reviewing zipalertinib for use after platinum-based chemotherapy fails, with a decision expected next February. Under a 2022 deal, Cullinan is set to receive $30 million upon approval for second-line use and $100 million for a first-line nod, with the partners splitting U.S. Pretax profits equally.
