Abstract 133TiP
Background
Anti–programmed cell death protein 1 (PD-1) and PD ligand 1 (PD-L1) monotherapy or in combination with chemotherapy is the standard of care for first-line treatment of PD-L1–positive locally advanced and metastatic non–small cell lung cancer (mNSCLC) in the absence of activating mutations. The addition of antiangiogenic agents to standard first-line treatment with a PD-L1 inhibitor and platinum-based chemotherapy has shown modest efficacy in patients with nonsquamous mNSCLC. Ivonescimab, a first-in-class investigational bispecific antibody against PD-1 and vascular endothelial growth factor, showed promising clinical efficacy in a phase III trial (HARMONi-2) in China. In HARMONi-2, progression-free survival (PFS) improved significantly in patients with PD-L1–positive (tumor proportion score [TPS] ≥1%) advanced NSCLC with ivonescimab compared with pembrolizumab (median PFS, 11.14 and 5.82 months, respectively; hazard ratio, 0.51; P < 0.0001). Results of the trial also showed an acceptable safety profile for ivonescimab, including in patients with squamous and non-squamous NSCLC.
Trial design
HARMONi-7 (NCT06767514) is a randomized, double-blind, global phase III study to compare the efficacy and safety of ivonescimab versus pembrolizumab monotherapy in patients with stage IV mNSCLC who have not previously received systemic therapy for metastatic disease and whose tumors show high PD-L1 expression (TPS ≥50%) and no known activating mutations. Approximately 780 patients will be randomly assigned (1:1) to receive ivonescimab 20 mg/kg or pembrolizumab 200 mg every 3 weeks for up to 24 months. Randomization will be stratified according to histology, presence or absence of brain metastases at study entry, and geographic region. The primary end points are overall survival and PFS (assessed by independent radiology review committee per RECIST v1.1). Secondary end points are objective response rate, disease control rate, duration of response, safety, pharmacokinetics of ivonescimab, and immunogenicity.
Clinical trial identification
NCT06767514.
Editorial acknowledgement
Editorial and medical writing assistance was provided by Jennifer McKinney, PhD, at MEDiSTRAVA (San Francisco, CA, USA).
Legal entity responsible for the study
Summit Therapeutics, Inc.
Funding
Summit 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, Invited Speaker, Steering Committee Member PALOMA-3 trial: Janssen; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Janssen, Cullinan Oncology; Financial Interests, Personal and Institutional, Invited Speaker: MSD, Arrivent, Bayer; Non-Financial Interests, Personal, Other, Scientific Commitee for Lung Cancer Guideline: AIOM; Non-Financial Interests, Personal, Officer, ESMO Council Member & Chair of Communication Committee: ESMO; Non-Financial Interests, Personal, Officer, Chair of Communication Committee: ESMO; Non-Financial Interests, Personal, Officer, Council Member: ESMO. N. Girard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Regeneron, AbbVie, Amgen, Lilly, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen, Pierre Fabre, Beigene; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Pfizer, Amgen, MSD, Sanofi, Gilead, Janssen; Financial Interests, Personal, Officer: edimark; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Personal, Other, Family member is an employee: AstraZeneca. D. Rodriguez Abreu: Financial Interests, Personal, Advisory Board: MSD, Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Eli Lilly, Incyte, Merck Serono; Financial Interests, Personal, Invited Speaker: MSD, Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Eli Lilly, Merck Serono; Financial Interests, Personal, Other, Travel expenses: MSD, Novartis, Roche/Genentech, Pfizer. M. Gumus: Financial Interests, Institutional, Advisory Role: MSD, Roche, Novartis; Financial Interests, Institutional, Research Grant: Roche, Amgen; Financial Interests, Institutional, Other: Roche, Novartis, Pfizer, Janssen. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Boehringer Ingelheim, Beigene, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Merk, MSD, Pfizer, Roche, Sanofi, Yunhan, Eli Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Takeda, Amgen, Daiichi Sankyo; Non-Financial Interests, Personal, Leadership Role: Chinese Thoracic Oncology Group (CTONG); Non-Financial Interests, Personal, Other, WCLC 2020 Conference Chair: IASLC; Non-Financial Interests, Personal, Leadership Role, Past President: Chinese Society of Clinical Oncology (CSCO); Non-Financial Interests, Personal, Other, Editorial Board member of Ann Oncology and ESMO Open: ESMO. K. Syrigos: Non-Financial Interests, Institutional, Principal Investigator: SOTIRIA Thoracic General Hospital of Athens. R. Ramlau: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, Pfizer, MSD, BMS, Novartis, Takeda, Parexel; Financial Interests, Personal, Invited Speaker: Roche, Boehringer Ingelheim, Novartis, Pfizer, Amgen, BMS, MSD, Merck, AstraZeneca, Parexel, Bioatla Inc, Janssen-Cilag, AstraZeneca, MAIA Biothechnology, Cantargia AB, Shanghai Henlius Biotech, BioNtech SE, Arcus Biosciences Inc. E.S. Santos: Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Genentech, Lilly, Pharmacosmo, Jazz Pharmaceuticals, Merck, Novocure, Pfizer, Regeneron, Coherus, Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca, AbbVie, Sanofi, Regeneron, Novartis, Johnson & Johnson, Boehringer Ingelheim, Novocure. D. Berz: Financial Interests, Personal, Full or part-time Employment: Valkyrie Clinical Trial; Financial Interests, Personal, Leadership Role: Jazz Pharmaceuticals, Sun Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: EMD Serono, Jazz Pharmaceuticals; Financial Interests, Personal, Other, Honoraria: Sun Pharma, Jazz Pharmaceuticals, EMD Serono; Financial Interests, Personal, Funding: Ascendis Pharma; Boehringer Ingelheim; BeiGene; BioNTech; Black Diamond Therapeutics; Bristol-Myers Squibb; eFFECTOR Therapeutics; Faeth Therapeutics; G1 Therapeutics; Genprex; Hongyun Biotech; Incyte; InhibRx; Mirati Therapeutics; Seagen; WhiteOak; Xencor. C. Gandhi: Financial Interests, Institutional, Principal Investigator: BRCR Global. N. Vokes: Financial Interests, Personal, Advisory Role: Oncocyte, Lilly, Sanofi, Regeneron, Amgen, Xencor, AstraZeneca, Tempus, Pfizer, Summit Therapeutics, OncoHost, Guardant; Financial Interests, Institutional, Other: EMD Serono, IDEAYA, Amgen, Summit Therapeutics, Regeneron, Sanofi; Financial Interests, Personal, Other: Regeneron; Financial Interests, Institutional, Research Grant: Circulogene, Nebraska Oncology Society, Scienomics Group, Grace, OncLive, OMNI-Oncology, Guardant, HMP Global, Medlive, PlatformQ Health, Targeted Oncology, MJH, Cardinal Health; Financial Interests, Institutional, Funding: Mirati; Non-Financial Interests, Personal, Other: Circulogene. B. Wang: Financial Interests, Personal, Advisory Board: AstraZeneca, Gilead, BeiGene. J. Rotow: Financial Interests, Personal, Advisory Board: AstraZeneca, BioAtla, BMS, Boehringer Ingelheim, Daiichi Sankyo, Genentech, G1 Therapeutics, Gilead, Johnson and Johnson, Jazz, Merus, Novocure, Pfizer, Summit, Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Pfizer, Regeneron; Financial Interests, Institutional, Invited Speaker: AbbVie, AstraZeneca, Bicycle Therapeutics, BioAtla, Blueprint Medicines, Daiichi Sankyo, Enliven, EpimAb, Lilly, ORIC, RedCloud, Summit, Black Diamond, Synthekine, ImmunityBio. P.K. Paik: Financial Interests, Personal, Advisory Board: Summit Therapeutics, EMD Serono, Janssen; Financial Interests, Institutional, Research Grant: Summit Therapeutics, EMD Serono, Novartis, Bicara. J. Weiss: Financial Interests, Personal, Stocks/Shares: Achilles Therapeutics, Nektar, Vesselon, Nuvalent, Lyell Immunopharma, En Fuego Therapeutics, Vertex, Merus, Revolution Medicines; Financial Interests, Personal, Advisory Role: AstraZeneca, EMD Serono, G1 Therapeutics, Jounce Therapeutics, Nanobiotix, BeiGene, Merck, Gilead Sciences, PDS Biotechnology, Amgen, Catalyst Pharmaceuticals; Financial Interests, Institutional, Research Grant: Merck, AstraZeneca/MedImmune, G1 Therapeutics, Immunicum, Loxo/Lilly, Mirati Therapeutics, Sumitomo Dainippon Pharma Oncology, Boehringer Ingelheim, PDS Biotechnology, Genmab, Iovance Biotherapeutics Nurix, TScan Therapeutics, Inspirna, Janux Therapeutics. J. Agulnik: Financial Interests, Personal, Advisory Board: AZ, Merck, Amgen, EMD Serono, BMS, Takeda, Roche, Sanofi, Janssen; Financial Interests, Personal, Invited Speaker: BI. X. Bai: Financial Interests, Personal, Stocks/Shares: Karyopharm Biogen, Titan; Financial Interests, Institutional, Full or part-time Employment: Summit Therapeutics. P. McGovern: Financial Interests, Institutional, Full or part-time Employment: Summit Therapeutics. A. Calles Blanco: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche, Lilly, Merck Sharp & Dohme, Novartis, Bristol Myers Squibb, Takeda, Sanofi, Janssen, Regeneron; Financial Interests, Personal, Other, Speaker honoraria: Bayer; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Institutional, Research Grant, Drug-only for Investigator-initiated trial.: Merck Sharp & Dohme.