1254MO - Safety and anti-tumour activity of zipalertinib in NSCLC patients (pts) with EGFR exon 20 insertion (ex20ins) mutations who received prior amivantamab

Background

Zipalertinib (CLN-081, TAS6417) is a novel EGFR TKI which demonstrated a confirmed objective response rate (ORR) of 41% and manageable safety in a phase 1/2a study in pts with ex20ins NSCLC after prior platinum-containing chemotherapy (JCO 2023). Here we present data from the phase 2b REZILIENT1 study of zipalertinib cohort C pts with EGFR ex20ins mutant NSCLC that progressed after prior amivantamab.

Methods

Pts that had progressed after at least 1 prior treatment including amivantamab were enrolled to receive zipalertinib at 100 mg oral twice daily. Tumor response was assessed by the investigator per RECIST v1.1. Stable, asymptomatic, or treated brain metastases were allowed.

Results

As of the 29 March 2024 data cut-off (DCO), 45 pts had been enrolled with median age of 62 years (33-85), median lines of prior therapy 3 (1-6), prior platinum-based chemotherapy 43 pts (96%), prior anti-PD1/L1 20 pts (44%), prior EGFR TKIs 22 pts (49%), and history of brain metastasis 22 pts (49%). Treatment-related AEs (TRAEs) occurring in ≥ 10% of pts were rash (38%), paronychia (36%), anemia (24%), dry skin (20%), dermatitis acneiform (16%), nausea (16%), and stomatitis (11%). Grade 3 TRAEs were reported in 14 pts (31%): occurring in included anemia (4), rash (3), and pneumonitis/ILD (3). There were no grade 4 or 5 TRAEs. TRAEs leading to dose reductions and discontinuations occurred in 3 pts (7%) each. At DCO, 30 pts were evaluable for response (at least 2 on treatment assessments or PD/death), of which 1 pt (3%) had CR, 11 pts (37%) had partial response (PR), and 15 (50%) had stable disease (SD). The ORR was 40% and disease control rate (CR + PR + SD) was 90%. Median duration of response was not yet estimable and median PFS was 9.7 months.

Conclusions

This is the first report to systematically characterize the anti-tumor activity of a new irreversible and selective EGFR ex20ins TKI, in heavily treated pts with NSCLC harboring EGFR ex20ins mutations who have received prior amivantamab. In this amivantamab resistant setting, zipalertinib demonstrated promising efficacy, similar to pts that progressed after platinum-based chemotherapy alone and had a manageable safety profile.

Clinical trial identification

NCT04036682.

Editorial acknowledgement

Legal entity responsible for the study

Cullinan Therapeutics, Inc.

Funding

Cullinan Therapeutics, Inc.

Disclosure

A. Passaro: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, eCancer; Financial Interests, Personal and Institutional, Steering Committee Member, Steering Committee Member PALOMA-3 trial: Janssen; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Janssen; Financial Interests, Personal and Institutional, Local PI: MSD; Financial Interests, Personal and Institutional, Steering Committee Member: Arrivent, Bayer; Financial Interests, Institutional, Coordinating PI: Cullinan Oncology; Non-Financial Interests, Other, Scientific Committee for Lung Cancer Guideline: AIOM; Non-Financial Interests, Officer, ESMO Council Member & Chair of Communication Committee: ESMO; Non-Financial Interests, Officer, Chair of Communication Committee: ESMO; Non-Financial Interests, Officer, Council Member: ESMO. H.A. Yu: Financial Interests, Personal, Advisory Board: Cullinan, AstraZeneca, Daiichi Sankyo, Black Diamond, Taiho, Amgen, Janssen; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Pfizer; Financial Interests, Institutional, Local PI: Janssen, Blueprint; Financial Interests, Institutional, Steering Committee Member: Daiichi Sankyo, Cullinan, Taiho, Systimmune, Black Diamond. D. Nguyen: Financial Interests, Personal, Advisory Board, 5/6/23, Advisory Panel on mEGFR lung cancer in AAPI population: Janssen; Non-Financial Interests, Other, Panel discussion, non-compensated, regarding Equity, etc.: Takeda; Other, Safety Review Committee, non-compensated, clinical trial: Seagen; Other, Funding for publication fees: Novartis, Pfizer. V.H.F. Lee: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Roche, Merck Sharp & Dohme, Boston Scientific, Takeda, ZaiLab; Financial Interests, Institutional, Research Grant: AstraZeneca, Boston Scientific. R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, Yuhan, Janssen, Merck Serono, Puma Biotech, Thermo Fisher; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Pfizer. H. Daga: Financial Interests, Personal, Invited Speaker: Chugai pharmaceutical, AstraZeneca. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche, Regeneron, Genmab; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Steering Committee Member: Novartis. S. Kim: Non-Financial Interests, Institutional, Advisory Role: AstraZeneca, Janssen, Therapex; Financial Interests, Institutional, Funding: Yuhan. O.J. Juan Vidal: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Roche/Genentech, Lilly, Takeda, AstraZeneca, Janssen; Financial Interests, Personal, Other, Travel expenses: MSD; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squib, AMGEN, Roche/Genentech, Pfizer; Financial Interests, Institutional, Funding: AstraZeneca. Z. Piotrowska: Financial Interests, Personal, Invited Speaker, 3/2023: Participated in a Janssen-sponsored satellite symposium at ELCC 2023.: Janssen; Financial Interests, Personal, Advisory Board, 5/2022 Janssen Ad Board9/2022: Janssen Ad Board (ESMO 2022)11/2023: Janssen Papillon Ad Board3/2024 Janssen Ad Board: Janssen; Financial Interests, Personal, Advisory Board, 9/2022: Takeda Ad Board: Takeda; Financial Interests, Personal, Invited Speaker, 3/2024: Honorarium for Eli Lilly satellite program at ELCC 2024: Eli Lilly; Financial Interests, Personal, Advisory Board, 9/2022: Zipalertinib Ad Board at ESMO 202211/2023: Zipalertinib Ad Board: Taiho; Financial Interests, Personal, Advisory Board, 1/2023: Sanofi Ad Board: Sanofi; Financial Interests, Personal, Advisory Board, 6/2023 Merck Ad Board: Merck; Financial Interests, Personal, Advisory Board, 9/2023: Daiichi Ad Board at WCLC 2023.: Daiichi Sankyo; Financial Interests, Personal, Other, 1/2024 (ongoing): Member of Genentech DSMC.: Genentech; Financial Interests, Personal, Invited Speaker, Honoraria for OncLive sponsored educational programs (non-CME).: OncLive; Financial Interests, Personal, Invited Speaker, Honoraria for RTP-sponsored educational programs (CME): Research to Practice; Financial Interests, Personal, Invited Speaker, Honoraria for CCO-sponsored educational programs.: Clinical Care Options; Financial Interests, Personal, Advisory Board, 6/2023: Bayer Ad Board3/2024: Bayer Ad Board at ELCC: Bayer; Financial Interests, Personal, Invited Speaker, Honoraria for speaking at and co-chairing PeerView CME programs.: PeerView; Financial Interests, Personal, Invited Speaker, Honoraria for participation in educational programs.: Medscape, Plexus, Physicians Education Resource, Targeted Oncology/MJH Holdings, Aptitude Health; Financial Interests, Personal, Advisory Board, 12/2023: BI Ad Board at NACLC: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, 10/2023: Honorarium for speaking at BI-sponsored satellite symposium at ESMO 2023.: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, Honoraria for participation in CME programs (7/2022 and 7/2023): Philips Gilmore; Financial Interests, Personal, Invited Speaker, Honoraria for participation in CME program (10/2022 and 10/2023): MedStar Health; Financial Interests, Personal, Advisory Board, 8/2022: AZ Ad Board6/2023: AZ Ad Board - ASCO6/2023: AZ Roundtable- ASCO10/2023: AZ Ad Board- ESMO: AstraZeneca; Financial Interests, Personal, Invited Speaker, 10/2022: Honorarium for CME program.: Ology; Financial Interests, Personal, Invited Speaker, Honorarium for educational program.: Dava Oncology; Financial Interests, Personal, Invited Speaker, Honorarium for participation in educational programs.: CEC Oncology; Financial Interests, Personal, Advisory Board, 9/2023: Blueprint Ad Board: Blueprint Medicines; Financial Interests, Personal, Invited Speaker, 8/2023: Honorarium for speaking at internal educational program.: Blueprint Medicines; Financial Interests, Personal, Full or part-time Employment, My husband is a full-time employee of Blue Cross Blue Shield of Massachusetts.: Blue Cross Blue Shield of Massachusetts; Financial Interests, Institutional, Research Grant, Institutional research funding for clinical trial: Novartis, Tesaro/GSK; Financial Interests, Institutional, Local PI, Institutional research funding for clinical trial: Takeda, Spectrum, Daiichi Sankyo, AbbVie, Janssen, Blueprint, Phanes Therapeutics, Roche; Financial Interests, Institutional, Coordinating PI, Institutional research funding for clinical trial: AstraZeneca, Cullinan; Financial Interests, Steering Committee Member: AstraZeneca; Non-Financial Interests, Principal Investigator: Cullinan, AstraZeneca. E.K. Keeton: Financial Interests, Personal, Full or part-time Employment: Cullinan Therapeutics; Financial Interests, Personal, Stocks/Shares: Cullinan Therapeutics. T. Liu: Financial Interests, Personal, Full or part-time Employment: Cullinan Therapeutics; Financial Interests, Personal, Stocks/Shares: Cullinan Therapeutics, BMS. S. Li: Financial Interests, Institutional, Full or part-time Employment: Culliunan Therapeutics; Financial Interests, Personal, Stocks/Shares: Culliunan Therapeutics. J. Jones: Financial Interests, Personal, Officer, Chief Medical Officer: Cullinan Oncology; Financial Interests, Personal, Stocks/Shares: Cullinan Oncology. G. Ruiter: Financial Interests, Institutional, Local PI: AstraZeneca, Daiichi Sankyo, Cullinan Oncology, Boehringer Ingelheim, Merus, Bayer, Bristol Myers Squibb, Pierre Fabre, Navire BridgeBio, Ikena Oncology, Scorpion Therapeutics, Taiho Oncology, Revolution Medicine. All other authors have declared no conflicts of interest.