Earlier this year, Cullinan Therapeutics said its lead candidate hit the bull's-eye in a midstage cancer trial but stayed mum on the details. Now, the biotech is revealing the results that have prompted the company and partner Taiho Oncology to pursue an accelerated approval.
Twice-daily oral doses of the candidate were tied to an overall objective response rate (ORR) of 35% in patients with pretreated EGFR ex20ins non-small cell lung cancer (NSCLC), while also demonstrating a manageable safety profile, according to a May 22 release. The candidate is a novel EGFR tyrosine kinase inhibitor called zipalertinib.
The data will be shared June 1 at this year’s American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
The drug was tested in the pivotal phase 2b cohort of a phase 1/2 study run in collaboration with Japan’s Taiho Oncology. The open-label trial, dubbed Rezilient1, launched in 2019 and has an estimated enrollment of 280 patients with advanced or metastatic cancer.
The overall efficacy population included 176 patients who received at least one dose of 100 mg zipalertinib with at least eight months of follow-up by the December 2024 cutoff. These patients had received a median two prior therapies and 39% had a history of brain metastases.
The pair reported the 35% confirmed ORR with a median duration of response (mDOR) of 8.8 months at 24 months, hitting both of the study’s primary endpoints.
For 125 patients who had previously received platinum-based chemotherapy only, the ORR rose to 40% with a mDOR of 8.8 months, findings that are consistent with the trial’s phase 1/2a results.
Among 30 patients with prior chemo and Johnson & Johnson’s amivantamab (sold as Rybrevant) without the addition of other prior ex20ins-targeted therapy, the ORR was 30% with a mDOR of 14.7 months. This is compared to 51 participants who had received prior chemo and amivantamab—with or without other ex20ins-targeted therapy—in whom the ORR was 24% and the mDOR was 8.5 months.
For 68 patients with brain metastases, the ORR was 31% with a mDOR of 8.3 months.
As for safety, 244 patients who received at least one dose of 100 mg zipalertinib were included in the analysis. The most common treatment-related adverse events (TRAEs) were nail infections called paronychia, occurring in 38.5% of patients, and rash in 30.3% of participants.
Though the majority of TRAEs were classified as grade 1 or 2 events, the most common of the more severe events was anemia, which occurred in 7% of patients, according to the release.
The companies plan to submit an approval application to the FDA in relapsed or refractory EGFR ex20ins NSCLC during the second half of this year, according to a May 8 Cullinan earnings report.
“People living with EGFR ex20ins NSCLC urgently need well-tolerated targeted therapies with durable clinical benefit,” Helena Yu, M.D., thoracic medical oncologist and early drug development specialist at the Memorial Sloan Kettering Cancer Center, said in the May 22 release. “It is encouraging to see a program that can potentially offer a meaningful option for some of the sickest patients with lung cancer. The findings from the REZILIENT1 trial may support zipalertinib as a potential new oral treatment option for patients whose disease progressed after prior therapies.”
Zipalertinib, which was developed by Taiho, has snagged breakthrough therapy designation from the FDA.
Back in 2019, Cullinan joined forces with Taiho to develop the candidate, with Taiho granting the U.S. biotech exclusive ex-Japan rights to zipalertinib. But, a few years later, Cullinan had to return some of the commercial rights to Taiho for $275 million upfront. Taiho elected to claw back rights to more markets, with the two now co-developing the drug in the U.S. and the Otsuka Holdings outfit taking the baton in all other ex-China markets.