Abstract 345TiP
Background
The immune checkpoint protein B7-H3 has limited expression in normal tissues but is overexpressed in multiple solid tumours, including lung cancers. GSK’227 (HS-20093) is a novel ADC composed of a fully human anti-B7-H3 monoclonal antibody linked to a topoisomerase I inhibitor. GSK’227 has shown acceptable safety and promising anti-tumour activity in Asian patients with advanced solid tumours (NCT05276609; NCT05830123). This study (NCT06551142) will evaluate the safety, tolerability, efficacy and pharmacokinetics (PK) of GSK’227 monotherapy and combined with SoC in patients with advanced solid tumours, including lung cancers, in a global population.
Trial design
This Phase I, open-label, dose-escalation (1a) and expansion (1b) study will enrol ∼280 adults with histologically confirmed advanced solid tumours and progression on/intolerance to SoC, measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, Eastern Cooperative Oncology Group performance status 0–1 and no prior anti-B7-H3 therapy. Phase Ia will assess GSK’227 dose escalation as monotherapy and combined with SoC. In the combination arm, patients will receive intravenous GSK’227 every 3 weeks (Q3W) combined with SoC (for lung cancers: atezolizumab/durvalumab/pembrolizumab ± cisplatin/carboplatin) until progression, toxicity, loss to follow-up or death. Phase Ia primary endpoints are safety and tolerability. Secondary endpoints include objective response rate (ORR), disease control rate, duration of response, immunogenicity and PK. Phase Ib will assess multiple solid tumour cohorts; the primary endpoint is ORR, and secondary endpoints include safety, tolerability and PK. Efficacy will be assessed per RECIST v1.1, with imaging conducted Q6Wthen Q12W (>24weeks). Safety follow-up will be assessed at 30, 60 and 90 (±7) days after the last dose. Safety, tolerability and efficacy analyses will be conducted using descriptive statistics and, for efficacy analyses, point estimates with 2-sided 95% confidence intervals.
Clinical trial identification
NCT06551142.
Editorial acknowledgement
Medical writing support was provided by Nicholas Thomas, PhD, at Fishawack Indicia Ltd, part of Avalere Health, and was funded by GSK.
Legal entity responsible for the study
GSK.
Funding
GSK (Study 223054).
Disclosure
H.R. Kim: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Bridgebio Therapeutics; Financial Interests, Personal, Advisory Role: Bayer, AstraZeneca, Bristol Myers Squibb, Takeda, Yuhan; Financial Interests, Personal, Funding: Yonsei Lee Youn Jae Fellowship. P. Cassier: Financial Interests, Personal, Other, Consulting: OSE Immunotherapeutics, Bristol Myers Squibb/Celgene, Boehringer Ingelheim, Brenus Pharma, Scenic Biotech; Financial Interests, Personal, Other, Travel expenses: Roche, OSE Immunotherapeutics, Novartis; Financial Interests, Personal, Funding: Novartis, Roche/Genentech, Lilly, Blueprint Medicines, AstraZeneca, AbbVie, Bristol Myers Squibb, Merck Sharp & Dohme, Taiho Pharmaceutical, Toray Industries, Transgene, Loxo, GSK, Innate Pharma, Janssen, Boehringer Ingelheim, Daiichi Sankyo/UCB Japan, Ad; Non-Financial Interests, Personal, Other, Uncompensated relations: ReACT Therapeutics. G. Daniele: Financial Interests, Personal, Speaker’s Bureau: Bayer, AstraZeneca, Gilead; Financial Interests, Personal, Other, Travel expenses: Bayer, Roche, AstraZeneca, Gilead. G. Curigliano: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, Menarini, Bristol Myers Squibb, Merck; Financial Interests, Personal, Other, Consulting: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, Menarini, Bristol Myers Squibb, Merck; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, Menarini, Bristol Myers Squibb, Merck; Financial Interests, Personal, Funding: Merck, AstraZeneca; Financial Interests, Personal, Other, Travel expenses: Daiichi Sankyo. J. Hilton: Financial Interests, Personal, Sponsor/Funding, Consulting: Bristol Myers Squibb, GSK, AstraZeneca, Pfizer, Gilead, Daiichi Sankyo, Novartis; Financial Interests, Personal, Funding: GSK. A. Italiano: Financial Interests, Personal, Other, Honoraria: Bayer, Daiichi Sankyo, Epizyme, IPSEN, Lilly, Novartis, Roche; Financial Interests, Personal, Other, Consulting: Bayer, Daiichi Sankyo, Epizyme, Immune Design, Lilly, Roche; Financial Interests, Personal, Funding: AstraZeneca/MedImmune, Bayer, Merck Serono, MSD Oncology, PharmaMar, Roche; Financial Interests, Personal, Royalties: Bristol Myers Squibb. S. Koganemaru: Financial Interests, Personal, Funding: Amgen, Bristol Myers Squibb, Daiichi Sankyo, AbbVie, MSD, Incyte, Eisai Inc. R.D. Kowalyszyn: Financial Interests, Personal, Other, Consulting: Daiichi Sankyo, Takeda, Bristol Myers Squibb, Merck, Gador, Astellas, Merck Serono, Novartis BM; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Funding: Bristol Myers Squibb, MSD, Astellas Pharma, Merck Serono, Novartis, Roche, Eli Lilly, Gemabiotech, Nektar Therapeutics, Poliphor, AstraZeneca, Pfizer; Financial Interests, Personal, Other, Travel expenses: from J&J, GSK, Novartis, Gador, Pfizer, Roche, AstraZeneca, Elea. P.M. Lorusso: Financial Interests, Personal, Other, Consulting: AbbVie, Roche-Genentech, Takeda, SOTIO, Agenus, IQVIA, Pfizer, GSK, QED Therapeutics, AstraZeneca, EMD Serono, Kyowa Kirin Pharmaceutical Development, Kineta Inc., Zentalis Pharmaceuticals, Molecular Templates, ABL Bio, STCube Pharmaceuticals, I-Mab, Seag. V. Moreno Garcia: Financial Interests, Personal, Full or part-time Employment: START; Financial Interests, Personal, Other, Consulting: Merck, Bristol Myers Squibb, Bayer, Janssen Oncology, Roche, Basilea, Affimed Therapeutics, AstraZeneca, AbbVie; Financial Interests, Personal, Speaker’s Bureau: Bayer, Pierre Fabre; Financial Interests, Personal, Other, Travel expenses: Sanofi/Regeneron; Financial Interests, Personal, Expert Testimony: Medscape/Bayer, Nanobiotix; Financial Interests, Personal, Funding: AbbVie, ACEA Biosciences, Adaptimmune, Amgen, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eisai, E-therapeutics, GSK, Janssen, Menarini, Merck, Nanobiotix, Novartis, Pfizer, PharmaMar, PsiOxus Therapeutics, Puma Biote; Financial Interests, Personal, Other, Other relationship: Bristol Myers Squibb. H.A. Perroud: Financial Interests, Personal, Other, Travel expenses: GSK, Pfizer, ELEA. W.M. Saif: Financial Interests, Personal, Other, Consulting: US World Meds; Financial Interests, Personal, Funding: Genentech, SpringWorks, IDEAYA, Yivia, Amal; Financial Interests, Personal, Royalties: UpToDate. N. Yamamoto: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Daiichi Sankyo/UCB Japan, Eisai; Financial Interests, Personal, Other, Consulting: Eisai, Boehringer Ingelheim, CMIC, Chugai Pharma, Healios, Merck, Mitsubishi Tanabe, Rakuten Medical Japan, Noile-Immune Biotech, Inc; Financial Interests, Personal, Funding: Chiome Bioscience, Otsuka, Chugai Pharma, Taiho Pharmaceutical, Eisai, Astellas Pharma, Novartis, Daiichi Sankyo, Lilly Japan, Boehringer Ingelheim, Takeda, Kyowa Hakka Kirin, Bayer, Pfizer, Ono Pharmaceutical, Janssen, MSD, AbbVie, Bristol Myers Squibb. A. Aziez, R. Anjum, J.C. Lamacchia, J. Huang: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks/Shares: GSK. S.N. Symeonides: Financial Interests, Personal, Advisory Board: Duke Street Bio, Eisai, Ellipses, Eugit Therapeutics, Exscientia, GreyWolf Therapeutics, MSD, Roche; Financial Interests, Personal, Speaker’s Bureau: Eisai, Ipsen, MSD; Financial Interests, Personal, Funding: MSD, Verastem; Financial Interests, Personal, Other, Research collaboration (as PI/CI): AstraZeneca, BioLineRx, BioNTech, Boston Pharmaceuticals, Corbus, Genentech, Grey Wolf Therapeutics, GSK, Incyte, Medannex, MSD, Nouscom, Nucana, Nuvectis, Pfizer, Roche, Salubris, Sapience, Scancell. V. Subbiah: Financial Interests, Personal, Other, Clinical trial support: GSK. All other authors have declared no conflicts of interest.