Efficacy and safety of sunvozertinib in prior platinum treated NSCLC patients with EGFR exon 20 insertion mutations: Primary analysis from the multinational WU-KONG1B pivotal study

BackgroundSunvozertinib (DZD9008) is a rationally designed, irreversible EGFR exon 20 insertion (EGFR exon20ins) inhibitor. It was approved in China based on results from a China-only WU-KONG6 study in 2023. Here, we report the results of primary analysis of an equivalent multinational phase 2 pivotal study (WU-KONG1B, NCT03974022).MethodsWU-KONG1B assessed anti-tumor efficacy of sunvozertinib, as the primary objective, in pre-treated NSCLC with EGFR exon20ins. The primary and key secondary endpoints were objective response rate (ORR) and duration of response (DoR) assessed by independent review committee (IRC), respectively.ResultsA total of 111 eligible patients were enrolled into the study and received sunvozertinib at 300 mg once daily. The primary efficacy analysis set included 107 patients post platinum-based chemotherapy: 57.9% Asian, 54.2% from Asia, 25.2% with baseline brain metastasis, 13.1% with prior amivantamab, 48.6% with prior onco-immunotherapy and 13.1% with EGFR TKI treatment. As of March 22, 2024, per IRC assessment, the best ORR was 53.3% (44.9% confirmed and additional 3.7% pending confirmation). With a median follow-up of 7 months, DoR was not reached, with 66.7% responders still responding. The anti-tumor efficacy (confirmed ORR) was comparable between different subgroups, including race (Asian vs. non-Asian, 48.4% vs. 40.0%), region (Asia vs. non-Asia, 48.3% vs 40.8%). In addition, anti-tumor efficacy was observed irrespective of prior anti-cancer therapies (e.g., amivantamab, onco-immunotherapy and EGFR TKIs), other demographics and disease characteristics, EGFR exon20ins subtypes and insertion location. The safety profile of sunvozertinib was similar to what has been previously reported, and clinically manageable.ConclusionsThe primary results of WU-KONG1B showed promising anti-tumor efficacy of sunvozertinib in advanced NSCLC with EGFR exon20ins, regardless of different subgroups. The updated results will be presented at the conference.Clinical trial identificationNCT03974022.Legal entity responsible for the studyDizal Pharmaceutical.FundingDizal Pharmaceutical.DisclosureL. Doucet: Financial Interests, Institutional, Coordinating PI: Dizal; Financial Interests, Institutional, Local PI: Mirati, MSD, Takeda, Novartis, Gilead. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, BMS, MSD, Novartis, Takeda, Pfizer, PharmaMar; Financial Interests, Institutional, Coordinating PI: Sanofi; Financial Interests, Personal, Local PI: Roche. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. J. Mazieres: Financial Interests, Personal and Institutional, Advisory Role: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo Pharmaceutical, Merck KGaA, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, Roche/Genentech. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc., Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. J. Bosch-Barrera: Financial Interests, Personal, Invited Speaker: MSD, BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche, Sanofi; Other, Relative (sister in law) working for this company: AstraZeneca. F. Ghiringhelli: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Amgen, Merck Serono, MSD. A. Bearz: Financial Interests, Personal, Advisory Board: Pfizer, Roche; Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Eli Lilly, Janssen, Novartis; Non-Financial Interests, Principal Investigator: Roche, Pfizer, Gilead, MSD. L.G. Paz-Ares: Financial Interests, Personal, Advisory Board, Speaker fees: Roche, MSD, BMS, AZ, Lilly, PharmaMar, BeiGene, Daiichi Sankyo, Medscape, PER; Financial Interests, Personal, Advisory Board: Merck Serono, Pfizer, Bayer, Amgen, Janssen, GSK, Novartis, Takeda, Sanofi, Mirati; Financial Interests, Personal, Other, Board member: Genomica, Altum sequencing; Financial Interests, Personal, Member of Board of Directors, Board member: Stab Therapeutics; Financial Interests, Institutional, Coordinating PI: Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme Corp, BMS, Janssen-Cilag international NV, Novartis, Roche, Sanofi, Tesaro, Alkermes, Lilly, Takeda, Pfizer, PharmaMar; Financial Interests, Personal, Coordinating PI: Amgen; Financial Interests, Other, Member: AACR, ASCO, ESMO; Financial Interests, Other, Foundation Board Member: AECC; Financial Interests, Other, President ASEICA (Spanish Association of CancerResearch): ASEICA; Financial Interests, Other, Foundation president: ONCOSUR; Financial Interests, Other, member: Small Lung Cancer Group. M. Tiseo: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Roche, Amgen, Takeda, MSD, Merck, BMS, Pfizer, Eli Lilly, Novartis, Janssen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Roche. E. Carcereny: Financial Interests, Personal, Invited Speaker: Takeda, MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Merck. G. Zalcman: Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Da Volterra, Inventiva Pharma, MSD Oncology, Pfizer, Roche; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb, Pfizer, Roche, Takeda; Financial Interests, Personal, Funding, Honoraria; Travel, Accommodations, Expenses: Lilly; Financial Interests, Personal, Funding, Travel, Accommodations, Expenses: AbbVie. V.P. Di Noia: Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Boehringer Ingelheim, MSD Oncology. J. de Castro Carpeño: Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dome, Pfizer, Roche; Financial Interests, Personal, Funding, Travel, Accommodations, Expenses: AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dome, Roche. L. Zheng: Financial Interests, Personal and Institutional, Full or part-time Employment: Dizal. J.C. Yang: Financial Interests, Institutional, Advisory Board: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Yuhan Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen, Gilead, Blueprint Medicine, Eisai, Sanofi, Taiho, BMS, Omega Therapeutics, AnHeart Therpeutics, Regeneron; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Coordinating PI: AstraZeneca, MSD; Financial Interests, Coordinating PI: Dizal Pharmaceutical; Financial Interests, Steering Committee Member: Numab, Merck, Daiichi Sankyo, Eli Lilly, Janssen, Arrivant, Cullinan; Financial Interests, Institutional, Steering Committee Member: Ipsen, Takeda Oncology; Non-Financial Interests, Member: IASLC, ASCO. P.A. Jänne: Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly, Voronoi, Daiichi Sankyo, Novartis, Sanofi, Takeda Oncology, Mirati Therapeutics, Trasncenta, Silicon Therapeutics, Syndax, Nuvalent, Bayer, Eisai, Allorion Therapeutics, Accutar Biotech, AbbVie, Duality Biologics, Blueprint Medicines, Dizal Pharma; Financial Interests, Personal, Advisory Board, Consulting fees for advice on diagnostic development: Biocartis; Financial Interests, Personal, Advisory Board, Consulting fee for advice on drug development: Merus, Frontier Medicines; Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development.: Hongyun Biotechnology; Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals, Allorion Therapeutics, Frontier Medicines; Financial Interests, Personal, Royalties, I receive post-marketing royalties from being an inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp: Lab Corp; Financial Interests, Institutional, Research Grant, Sponsored research agreement with my institution: AstraZeneca, Daiichi Sankyo, PUMA, Eli Lilly, Boehringer Ingelheim, Revolution Medicines, Takeda Oncology. All other authors have declared no conflicts of interest.