Taiho Oncology And Cullinan Therapeutics Report 27% Response Rate In REZILIENT1 And 30% Response Rate In REZILIENT2 Lung Cancer Trial

Author: Benzinga Newsdesk | September 09, 2025 04:49am

Taiho Oncology, Inc., and Cullinan Therapeutics, Inc., today announced new data from the REZILIENT1 and REZILIENT2 trials of zipalertinib, an oral EGFR tyrosine kinase inhibitor, in patients with advanced or metastatic non-small cell lung cancer (NSCLC). These data will be presented at the IASLC 2025 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer as mini oral presentations on September 9 during the "MA08 - Common and Uncommon EGFR Mutations, New Treatments in the Horizon" session, from 11:30 a.m. – 12:45 p.m. CEST.

 

A mini oral presentation will highlight updated data from the pivotal Phase 2b REZILIENT1 trial of zipalertinib, focused on patients with NSCLC harboring EGFR ex20ins mutations, who have been previously treated with amivantamab.1

A second mini oral presentation will highlight Phase 2b preliminary efficacy and safety results from the ongoing, uncommon non-ex20ins EGFR mutations cohort of the REZILIENT2 trial of zipalertinib in patients with advanced or metastatic NSCLC harboring ex20ins and uncommon non-ex20ins EGFR mutations.2

"We're pleased to share longer-term follow-up data from the REZILIENT1 study of zipalertinib for patients with NSCLC harboring EGFR ex20ins mutations who have been previously treated with amivantamab," said Zofia Piotrowska, MD, Associate Professor of Medicine, Harvard Medical School and lung cancer clinical oncologist at the Mass General Cancer Center. "Despite recent treatment advancements, a significant medical need exists for this patient population, underscoring the importance of these data."

"Uncommon non-exon 20 insertion EGFR mutations represent a significant clinical challenge, as they exhibit variable and often suboptimal responses to currently approved tyrosine kinase inhibitors," said Hibiki Udagawa, MD, PhD, thoracic medical oncologist, National Cancer Hospital East, Japan.  "We are pleased to present the interim data from the uncommon non-ex20ins EGFR mutations cohort from the REZILIENT2 trial, potentially demonstrating the need for novel, targeted therapeutic approaches for this patient population."

Authors reported results from the REZILIENT1 study of zipalertinib from the cohort of NSCLC patients with EGFR ex20ins mutations who received prior amivantamab therapy1

Summary of Efficacy - by Blinded Independent Central Review (BICR):

As of the June 2025 data cutoff, 84 post-amivantamab patients were enrolled in REZILIENT1 and received at least one dose of 100 mg zipalertinib. Patients had received a median of 3 prior lines of therapy, and 54.8% of patients had a history of brain metastases.

With follow-up of more than 9 months, zipalertinib demonstrated:

• In all patients (n=84), confirmed objective response rate (ORR) was 27.4% with median duration of response (mDOR) of 8.5 months, and the disease control rate (DCR) was 84.5%.
  
  
  
   
• In patients with prior amivantamab only (n=54), ORR was 31.5% with mDOR of 9.5 months, and the DCR was 87.0%.
  
  
  
   
• In patients with prior amivantamab and other ex20ins-targeted therapy (n=30), ORR was 20.0% with mDOR of 8.3 months, and the DCR was 80.0%.
  
  
  
   
• In patients with brain metastases who received prior amivantamab only (n=31), the systemic ORR was 29%.

Summary of Safety and Tolerability 

The safety analysis population included all post-amivantamab patients in REZILIENT1 who received at least one dose of 100 mg zipalertinib (n=84). The results showed that zipalertinib 100 mg twice daily demonstrated a manageable safety profile in patients who progressed on prior chemotherapy and amivantamab with no new safety signals.

The most common treatment-emergent adverse events (TEAEs, all-grade) were paronychia (41.7%), anemia (38.1%), rash (34.5%), nausea (28.6%), diarrhea (22.6%), dry skin (21.4%), dermatitis acneiform (21.4%) and dyspnea (20.2%).

The most common grade ≥3 TEAEs were anemia (15.5%), pneumonia (10.7%), dyspnea (6.0%), rash (3.6%), diarrhea (2.4%) and stomatitis (2.4%).

Authors reported results from the REZILIENT2 study of zipalertinib from the cohort of patients with NSCLC harboring uncommon non-exon 20 insertion EGFR mutations2 

Summary of Preliminary Efficacy –by Investigator

As of the March 2025 data cutoff, 40 patients were enrolled in the REZILIENT2 Cohort D and received zipalertinib 100 mg orally twice daily. Previously treated patients had received a median of 2 prior lines of therapy, and 30% of all patients enrolled, including treatment-naïve, had a history of brain metastases.

As of the data cut-off, zipalertinib demonstrated:

• In the overall efficacy population (n=40), confirmed ORR was 30% with a mDOR of 7.75 months, and the disease control rate (DCR) was 70%.
• In the treatment-naïve population (n=8), ORR was significantly higher (62.5%) compared to the previously treated patient population (n=32, ORR 21.9%).

Summary of Preliminary Safety and Tolerability 

The safety analysis population included all REZILIENT2 patients in Cohort D who received at least one dose of 100 mg zipalertinib (n=40). The results showed that zipalertinib 100 mg twice daily demonstrated a manageable safety and tolerability profile with no new safety signals.

The most common treatment-related adverse events (TRAEs, all-grade) were paronychia (47.5%), dermatitis acneiform (37.5%), stomatitis (32.5%), anemia (30.0%), diarrhea (22.5%), rash (20.0%), and dry skin (15.0%). The majority of TRAEs were grade 1 or 2.

The most common grade ≥3 TRAEs were paronychia (5.0%), pneumonitis and anemia (5.0%).

Posted In: CGEM