On September 13, 2026 Taiho Oncology, Inc., Taiho Pharmaceutical Co., Ltd., and Cullinan Therapeutics, Inc. (Nasdaq: CGEM) reported results from the Phase 3 REZILIENT3 trial evaluating zipalertinib plus chemotherapy versus chemotherapy alone in the first-line treatment of patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutation-positive non-small cell lung cancer (NSCLC). The data were presented at the International Association for the Study of Lung Cancer’s (IASLC) 2026 World Conference on Lung Cancer (WCLC) in Seoul, South Korea.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

As previously announced, REZILIENT3 met its primary endpoint of progression-free survival (PFS). The results released today show that the addition of zipalertinib to platinum-based chemotherapy provided a statistically significant and clinically meaningful median PFS improvement of 6.0 months (HR=0.50; 95% CI, 0.34-0.73; P=0.00015) as first-line treatment for advanced NSCLC patients with EGFR ex20ins mutations. At the interim overall survival analysis (30% event maturity), the hazard ratio for death for zipalertinib plus chemotherapy versus chemotherapy was 0.72 (95% CI, 0.42-1.23) with follow up ongoing.

"The combination of zipalertinib plus platinum-based chemotherapy in the REZILIENT3 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival for patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations," said Helena A. Yu, MD, Thoracic Medical Oncologist at Memorial Sloan Kettering Cancer Center and study investigator. "The combination also produced significantly higher response rates compared with chemotherapy alone. These findings support the potential of zipalertinib plus platinum-based chemotherapy as a first-line treatment option for this patient population. We are grateful to the patients and their families, as well as the investigators whose dedication made these results possible."

These late-breaking results from the planned interim analysis of REZILIENT3 were selected for presentation in the Presidential Symposium 2 at IASLC 2026 WCLC. The Presidential Symposium 2 is a premier plenary session featuring notable advances in lung cancer research and treatment with the potential to change clinical practice.

"The findings presented add to previously presented single agent zipalertinib data and support the potential of zipalertinib across multiple treatment settings. We are thankful to patients, their families, and caregivers for participation in REZILIENT3," said Harold Keer, MD, PhD, Chief Medical Officer of Taiho Oncology. "We are excited to discuss these results further with health authorities and collaborate to make zipalertinib available to patients in a timely manner."

"We believe these results mark a potentially important step forward in the treatment of EGFR exon 20 insertion mutation-positive non-small cell lung cancer," said Fabio Benedetti, MD, Global Chief Medical Officer, Taiho Pharmaceutical. "To address the unmet medical needs of patients and their families, we will continue working closely with Taiho Oncology and Cullinan to make this treatment available to patients who may benefit from it."

"The selection of REZILIENT3 for presentation in a Presidential Symposium reflects the importance of these findings for the lung cancer community," said Jeffrey Jones, MD, MBA, Chief Medical Officer, Cullinan Therapeutics. "The magnitude of progression-free survival benefit, together with improvements in response rates and duration of response seen in REZILIENT3, reinforce the potential for zipalertinib plus chemotherapy to play an important role in the first-line treatment of patients with EGFR exon 20 insertion mutation NSCLC."

Summary of Results:

After a safety lead-in (n=6), a total of 279 advanced NSCLC patients with EGFR ex20ins and no prior treatment for advanced disease were randomly assigned to receive zipalertinib 100mg BID plus chemotherapy (n=140) or chemotherapy alone (n=139). Baseline characteristics were balanced between the combination and the control arm, including age (66.5 vs. 64 years), sex (65.7% vs. 63.3% female), and brain metastases (31.4% vs. 31.7%), respectively.

At the pre-planned interim efficacy analysis after 122 PFS events, treatment with zipalertinib plus chemotherapy led to significantly longer median PFS than chemotherapy alone (14.5 vs. 8.5 months; HR: 0.50; 95% CI 0.34-0.73; P=0.00015). This PFS benefit was consistent across subgroups, including patients with brain metastases (HR: 0.38).

Objective response rate was higher with the combination therapy (65.0% vs. 40.3%), P<0.0001, with a longer median duration of response (14.2 vs. 9.9 months). At the interim overall survival (OS) analysis (30% maturity), the hazard ratio for death for zipalertinib plus chemotherapy as compared with chemotherapy was 0.72 (95% CI, 0.42-1.23). Continued follow-up of REZILIENT3 is ongoing to further characterize the OS benefit and exploratory endpoints (ClinicalTrials.gov number NCT05973773).

Summary of Preliminary Safety and Tolerability:

The observed adverse event (AE) profile of zipalertinib plus chemotherapy was generally consistent with the known safety profiles of the individual agents, and no new safety signals were observed. Grade ≥3 AEs occurred more frequently with the combination (87.1% vs. 54.4%), but these were primarily manageable hematologic AEs (58.6% vs. 28.7%). Grade ≥3 EGFR-related toxicities were infrequent, and those observed only in the combination arm included rash (10.7%) and diarrhea (1.4%).

Session information for the data presentation at WCLC 2026 is listed below:

Title: Zipalertinib plus Chemotherapy for 1st-line NSCLC with EGFR Exon 20 Insertions: Results from the Phase 3 Trial (REZILIENT3)
Presenting Author: Dr. Daniel Tan Shao Weng, Duke Health, Singapore
Session Name: PL03 Presidential Symposium 2 Including Lectureship Award Presentations
Session Type: Presidential Symposium 2, a premier plenary session featuring notable advances in lung cancer research and treatment
Session Date: Monday, September 14, 2026
Session Time: 8 a.m. KST
Location: Plenary, Hall D2, 3F

About the REZILIENT3 Trial

This multicenter, randomized, controlled, open-label global trial enrolled 285 adults with previously untreated, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations. The primary objective of this trial is to assess progression-free survival in the zipalertinib plus chemotherapy arm versus the chemotherapy arm.

About Zipalertinib

Zipalertinib (development code: CLN-081/TAS6417) is an orally available small molecule designed to target activating mutations in EGFR. The molecule was selected because of its ability to inhibit EGFR variants with exon 20 insertion mutations. Zipalertinib is designed as a next generation, irreversible EGFR inhibitor for the treatment of a genetically defined subset of patients with non-small cell lung cancer. Zipalertinib is investigational and has not been approved by any health authority.

Zipalertinib is being developed by Taiho Oncology, Inc., its parent company, Taiho Pharmaceutical Co., Ltd., and in collaboration with Cullinan Therapeutics, Inc. in the U.S.

About EGFR Exon 20 Insertion Mutations

NSCLC is a common form of lung cancer and up to 4% of all cases globally have EGFR ex20ins.1 In the United States, approximately 16% of patients with NSCLC harbor EGFR mutations,1 with insertions at exon 20 accounting for up to 12% of these mutations.

(Press release, Taiho, SEP 13, 2026, View Source [SID1234670786])