Taiho Oncology and Cullinan Therapeutics Share Promising REZILIENT1 Phase 1/2 Findings on Zipalertinib in Lung Cancer

Positive Findings from the REZILIENT1 Trial

On June 1, 2025, Taiho Oncology, Inc. in partnership with Cullinan Therapeutics, Inc. announced significant findings from the REZILIENT1 clinical trial, which were published in the well-respected Journal of Clinical Oncology. The research revolves around zipalertinib, a novel treatment aimed at patients with non-small cell lung cancer (NSCLC) possessing specific epidermal growth factor receptor (EGFR) mutations, particularly exon 20 insertions.

Overview of the REZILIENT1 Trial

REZILIENT1 is a Phase 1/2 global study meticulously designed to evaluate the safety and efficacy of zipalertinib among patients suffering from advanced NSCLC who have already undergone previous treatment. This trial highlights a go-forward strategy as it sets the foundation for what could be a breakthrough in targeted therapies for lung cancer patients facing these specific genetic challenges.

The trial incorporated a total of 176 patients, including 51 who were previously treated with amivantamab. The findings reveal a remarkable overall confirmed objective response rate (ORR) of 35.2%, indicating that a significant number of patients benefited from the treatment. Moreover, those patients who received prior platinum-based chemotherapy exclusively reflected an ORR of 40%, with a median duration of response (mDOR) reaching 8.8 months.

Safety Profile and Implications

Assessing the safety of zipalertinib, researchers confirmed that it maintained a manageable safety profile, akin to previously reported data. Remarkably, patients who had undergone prior treatment with amivantamab only, demonstrated a confirmed ORR of 30% alongside a mDOR that extended up to 14.7 months. Even those suffering from brain metastases showed promising results, with an ORR of 30.9% and an mDOR of 8.3 months.

“Despite advancements in treatment strategies for EGFR ex20ins-mutant NSCLC, oral targeted options remain limited for patients with such mutations. This trial endorses zipalertinib as a potential therapeutic avenue,” stated Dr. Zofia Piotrowska, the principal investigator and noted researcher in lung cancer at Massachusetts General Hospital Cancer Center.

Future Directions

As Taiho Oncology progresses, they are actively inviting participants for the Phase 3 REZILIENT3 trial (NCT05973773), a continuation of research that may solidify zipalertinib’s standing in future treatment protocols. The findings from REZILIENT1 not only solidify the drug's efficacy but also raise hopes for patients with limited treatment options, particularly among those with resilient mutations.

Zipalertinib, which targets selective genetic mutations while minimizing effects on wild-type EGFR, has gained Breakthrough Therapy Designation from the FDA, emphasizing its potential in transforming the treatment landscape for NSCLC. While the development remains investigational and awaits further approvals, the results thus far depict a bright future for targeted therapies in oncology.

Conclusion

The diligent research conducted by Taiho Oncology and Cullinan Therapeutics exhibits not just scientific progress but potential life-changing treatment options for countless individuals battling lung cancer. As these findings are presented at the forthcoming American Society of Clinical Oncology (ASCO) Annual Meeting, they could invigorate discussions around tailored treatment approaches in oncology, paving the way for improving patient care and outcomes.