Abstract 670P
Background
Zipalertinib, a novel, covalently binding oral EGFR tyrosine kinase inhibitor, demonstrated encouraging antitumor activity as a monotherapy in the phase I/2 REZILIENT1 trial for heavily pretreated pts with EGFR ex20ins-mutant NSCLC (ORR 41%; Piotrowska et al. J Clin Oncol. 2023), however the safety in combination with chemotherapy is not known. We report results from the safety lead-in to the randomized, controlled, open-label, global, phase III REZILIENT3 trial (NCT05973773) of zipalertinib plus 1L standard-of-care (SoC) chemotherapy vs chemotherapy alone in previously untreated patients with EGFR ex20ins-mutant NSCLC.
Methods
The safety lead-in (Part A) was designed to confirm the use of zipalertinib 100 mg PO BID in combination with SoC chemotherapy (pemetrexed [500 mg/m2]; carboplatin [AUC 5 mg/mL/min] or cisplatin [75 mg/m2] up to 4 cycles; D1 of each 21-day cycle) for the randomized Part B of the trial. Pts eligible for Part A had locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations, no prior treatment for advanced disease, ECOG ≤ 1, and adequate organ function. Primary endpoint in part A was occurrence of dose limiting toxicities (DLTs) during cycle 1.
Results
Between December 2023 and February 2024, 6 pts were enrolled and treated. Median age was 53 years, 83% were female, 33% had a baseline ECOG PS of 1. No new safety signals were observed with the combination treatment; no DLTs, serious adverse events (SAEs), or CTCAE > Grade 3 TEAEs were reported. The most common Grade 3 TEAEs were anemia, neutropenia, neutrophil count decreased, leukopenia, and lymphopenia (16.7% each) consistent with previous reports for platinum-based chemotherapy. There were no AEs leading to discontinuation of study treatment.
Conclusions
The combination of zipalertinib 100 mg BID and SoC platinum-based chemotherapy was safe and tolerable with no new safety signals observed for each regimen. Based on these data, the randomized Part B of REZILIENT 3 is currently ongoing with zipalertinib 100 mg BID in combination with 1L SoC chemotherapy in pts with EGFR ex20ins-mutant NSCLC.
Clinical trial identification
NCT05973773.
Editorial acknowledgement
Professional medical writing and editorial assistance was provided by Envision Pharma, funded by Taiho Oncology, Inc.
Legal entity responsible for the study
Taiho Oncology, Inc.
Funding
Taiho Oncology, Inc.
Disclosure
T. Kurata: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Pfizer, Bristol Myers, Takeda, Eli Lilly, Chugai, Nipponkayaku, Ono; Financial Interests, Institutional, Local PI: MSD, Takeda, Janssen, AstraZeneca, Daiichi Sankyo, chugai, Amgen, Novartis, Ono. Y. Fujiwara: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, AstraZeneca/MedImmune, Boehringer Ingelheim, Bristol Myers Squibb Japan, Chiome Bioscience, Chugai Pharma, Daiichi Sankyo/UCB Japan, Lilly Japan, Merck, MSD, Nihonkayaku, Novartis, Ono Pharmaceutical, Otsuka, Pfizer, Taiho Pharmaceutical, Takeda; Financial Interests, Institutional, Research Funding: AbbVie, Amgen, Anheart Therapeutics, AstraZeneca, Bristol Myers Squibb Japan, Chugai Pharma , Incyte, Lilly Japan, Merck Serono, MSD, Novocure, Taiho Pharmaceutical. K. Naoki: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Boehringer Ingelheim, Bristol-Meyers, Chugai Pharma, Daiichi Sankyo, Lilly, Merck, MSD, Novartis, Pfizer, Taiho Pharmaceutical; Financial Interests, Institutional, Research Funding: Boehringer Ingelheim, Chugai Pharma, Ono Pharmaceutical, Parexel/CALYX, Taiho Pharmaceutical. S. Viteri: Financial Interests, Personal, Advisory Board: Merck Healthcar KGAA Germany, Bristol Myers Squibb S.A. U, Ipsen, Affimed; Financial Interests, Personal, Invited Speaker: MSD de España SA; Financial Interests, Institutional, Advisory Board: Roche; Financial Interests, Institutional, Invited Speaker: Canon Medical; Financial Interests, Personal, Officer: Mi Cancer Center SLP; Financial Interests, Personal, Ownership Interest, Private Healthcare Practice: Mi Cancer Center SLP; Financial Interests, Institutional, Steering Committee Member: OSE immunotherapeutics; Financial Interests, Institutional, Local PI: Nuvalent, AbbVie, Genfleet, Dizal, Taiho, GSK, Anheart Therapeutics. T. Inoue: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb Japan, Chugai Pharma, MSD, Ono Pharmaceutical. N. Hangai: Financial Interests, Personal, Full or part-time Employment: Taiho Oncology; Financial Interests, Personal, Stocks or ownership: Biomarin; Roche; Sanofi; Stoke Therapeutics. L. Wei: Financial Interests, Personal, Full or part-time Employment: Taiho Oncology. R. Kawabata: Financial Interests, Personal, Full or part-time Employment: Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Stocks/Shares: Otsuka Holdings Co., Ltd. V. Wacheck: Financial Interests, Personal, Full or part-time Employment: Taiho Oncology; Financial Interests, Personal, Stocks or ownership: Taiho Oncology; Financial Interests, Personal, Licencing Fees or royalty for IP: Patent (Inst). M. Nishio: Financial Interests, Personal, Invited Speaker, lectures fee: Ono Pharmaceuticals; Financial Interests, Personal, Invited Speaker, lectures: Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Daiichi Sankyo, AstraZeneca, MSD, AbbVie, Takeda, Pfizer, Boehringer Ingelheim, Novartis, Nippon Kayaku, Merck, Janssen; Financial Interests, Personal, Invited Speaker, lectures: Lilly.