Cullinan Therapeutics and Taiho Oncology’s zipalertinib elicited promising response rates in two mid-stage studies of non-small cell lung cancer patients with typical and uncommon EGFR mutations.
Cullinan Therapeutics and Taiho Oncology touted promising efficacy and safety data for their investigational tyrosine kinase inhibitor zipalertinib in certain types of non-small cell lung cancer, showing data in a pair of presentations Tuesday.
One Phase I/II study, dubbed REZILIENT1, involved 84 patients with NSCLC who harbored exon 20 insertion mutations in the EGFR gene. Study participants had undergone a median of three previous lines of therapy, including with Johnson & Johnson’s bispecific antibody Rybrevant. Results, presented at the 2025 World Conference on Lung Cancer, revealed a 27.4% objective response rate (ORR) and 84.5% disease control rate (DCR). Median duration of response was 8.5 months.
Zipalertinib appeared to be more effective as a second-line option in patients who had only been previously exposed to Rybrevant. ORR was 31.5% in that subgroup and DCR Increased to 87%.
Analysts at William Blair expressed optimism about zipalertinib’s prospects. “We believe zipalertinib continues to show strong efficacy in previously treated (with both chemotherapy and Rybrevant) patients, which along with its favorable tolerability profile should bode well for potential uptake in the second-line setting,” the analysts wrote in a note to investors Tuesday afternoon.
Meanwhile, the second study, a Phase IIb trial called REZILIENT2, focused on patients with “uncommon” NSCLC mutations—non-exon 20 insertions in the EGFR gene—according to Tuesday’s release. Participants had likewise undergone prior lines of treatment, though Taiho and Cullinan did not specify that this had to be with Rybrevant.
Zipalertinib treatment elicited a 30% ORR and a 70% DCR in this group. Median duration of response was 7.75 months.
Taken together, according to the William Blair analysts, zipalertinib’s efficacy data on Tuesday point to the drug’s “strong activity” in these two NSCLC patient populations. Taiho and Cullinan are building up to a regulatory submission by the end of the year for NSCLC with EGFR exon 20 insertions, according to the analyst firm.
REZILIENT2, in particular, “could support a meaningful expansion opportunity” for zipalertinib into patients harboring uncommon non-exon 20 mutations, according to William Blair. There are no submission plans for this specific population yet, as per the analysts’ note, but Taiho and Cullinan are scheduled to present findings from the study at the upcoming ESMO Congress next month.
Several other biopharma players have released major lung cancer readouts in recent days. Merck and Daiichi Sankyo on Sunday announced that their antibody-drug conjugate ifinatamab deruxtecan yielded a 48.2% confirmed objective response rate in patients with extensive-stage small cell lung cancer. The partners reported three complete responses.
Also on Sunday, Summit Therapeutics released data from the Phase III HARMONi study of its closely watched bispecific antibody ivonescimab in NSCLC. The biotech had already announced in May that HARMONi fell short of its overall survival bar, but Sunday’s readout additionally showed that survival outcomes appeared to be better in Asian patients than those in Western countries.
