168TiP - A phase I dose escalation/expansion study of GSK5764227 (GSK’227), a B7-homolog 3 (B7-H3) protein targeted antibody-drug conjugate (ADC), in patients with advanced solid tumours

Background

B7-H3 is an immune checkpoint protein overexpressed in multiple solid tumours with limited expression in normal tissues. GSK’227 (HS-20093), a novel B7-H3-targeted ADC, is composed of a human anti–B7-H3 monoclonal antibody linked to a topoisomerase I inhibitor via a protease-cleavable linker and has shown acceptable safety and promising antitumour activity in patients of Asian origin with advanced solid tumours (NCT05276609; NCT05830123). The current study will evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of GSK’227 in patients with solid tumours in a global population.

Trial Design

This two-part (dose-escalation [1a] and expansion [1b]) global, open-label, Phase I study (NCT06551142) will enrol ∼260 patients. Key eligibility includes: aged ≥18 years, histologically confirmed advanced solid tumours with measurable disease per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1), Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no prior B7-H3 treatment. Eligible patients will receive intravenous GSK’227 every 3 weeks (Q3W) until progression, toxicity, loss to follow-up, or death. For Phase 1a, a Bayesian optimal interval design will be used to determine the maximum tolerated dose. Phase 1a primary endpoints are safety and tolerability, including incidences of adverse events (AEs) and serious AEs. Secondary endpoints include objective response rate (ORR), disease control rate, duration of response, immunogenicity, and PK. The Phase 1b primary endpoint is progression-free survival (extensive-stage small cell lung cancer cohort) or ORR (solid tumours cohort). Secondary endpoints include additional efficacy assessments, PK, safety and tolerability. For Phase 1a and 1b, efficacy will be assessed per RECIST v1.1, with imaging conducted Q6W from first dose then Q12W after 24 weeks. Safety follow-up will be conducted 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. Funding: GSK (Study 223054).

Clinical trial identification

NCT06551142.

Editorial acknowledgement

Medical writing support was provided by Avalere Health, funded by GSK.

Legal entity responsible for the study

GSK.

Funding

GSK.

Disclosure

G. Curigliano: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, Menarini, BMS, Merck; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, Menarini, BMS, Merck; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, Menarini, BMS, Merck; Financial Interests, Personal, Research Funding: Merck, AstraZeneca; Financial Interests, Personal, Other, Travel accommodation expenses: Daiichi Sankyo. P. Cassier: Financial Interests, Personal, Advisory Role: OSE Immunotherapeutics, Bristol Myers Squibb/Celgene, Boehringer Ingelheim, Brenus Pharma, Scenic Biotech; Financial Interests, Personal, Other, Travel: Roche, OSE Immunotherapeutics, Novartis; Financial Interests, Institutional, Research 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, Adlai Nortye, Alligator Bioscience, Amgen, C4 Therapeutics, Debiopharm Group, Exelixis, Incyte, ITeos Therapeutics, OSE Immunotherapeutics, Molecular Partners, Pierre Fabre, Relay Therapeutics, Sotio, Tango Therapeutics; Non-Financial Interests, Personal, Other, Uncompensated Relationships: ReACT Therapeutics. G. Daniele: Financial Interests, Personal, Speaker, Consultant, Advisor: Bayer, AstraZeneca, Gilead; Financial Interests, Personal, Other, Travel, accommodation, expenses: Bayer, Roche, AstraZeneca, Gilead. J. Hilton: Financial Interests, Personal, Advisory Board: BMS, GSK, AstraZeneca, Pfizer, Gilead, Daiichi Sankyo, Novartis; Financial Interests, Institutional, Research Funding: GSK. A. Italiano: Financial Interests, Personal, Other, Honoraria: Bayer, Daiichi Sankyo, Epizyme, IPSEN, Lilly, Novartis, Roche; Financial Interests, Personal, Advisory Role: Bayer, Daiichi Sankyo, Epizyme, Immune Design, Lilly, Roche; Financial Interests, Personal, Research Funding: AstraZeneca/ MedImmune, Bayer, Merck Serono, MSD Oncology, PharmaMar, Roche; Financial Interests, Personal, Royalties: BMS. S. Koganemaru: Financial Interests, Personal, Research Funding: Amgen, Bristol Myers Squibb, Daiichi Sankyo, AbbVie, MSD, Incyte, Eisai Inc. R. Kowalyszyn: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Takeda, BMS, Merck, Gador, Astellas, Merck Serono, Novartis BM; Financial Interests, Personal, Research Funding: BMS, MSD, Astellas Pharma, Merck Serono, Novartis, Roche, Eli Lilly, Gemabiotech, Nektar Therapeutics, Poliphor, AstraZeneca, Pfizer; Financial Interests, Personal, Other, Travel, accommodation, expenses: J&J, GSK, Novartis, Gador, Pfizer, Roche, AstraZeneca, Elea . P.M. Lorusso: Financial Interests, Personal, Advisory Role: 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. H.A. Perroud: Financial Interests, Personal, Other, Travel, accommodation, expenses: GSK, Pfizer, Elea. W. Saif: Financial Interests, Personal, Advisory Role: US World Meds; Financial Interests, Personal, Research Funding: Genentech, SpringWorks, Ideaya, Yivia, Amal; Financial Interests, Personal, Royalties: UptoDate. A. Aziez, R. Anjum, J.C. Lamacchia, H. Sembhi, N. Ratia: Financial Interests, Personal, Full or part-time Employment: GSK; Financial Interests, Personal, Stocks or ownership: GSK. N. Yamamoto: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Daiichi Sankyo/UCB Japan, Eisai; Financial Interests, Personal, Advisory Role: Eisai Recipient, Boehringer Ingelheim, CMIC, Chugai Pharma, Healios, Merck, Mitsubishi Tanabe, Rakuten Medical Japan, Noile-Immune Biotech, Inc; Financial Interests, Personal, Advisory Board: Chiome Bioscience, Otsuka,; Financial Interests, Institutional, Advisory Board: 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, Merck Serono, GSK, Sumitomo. All other authors have declared no conflicts of interest.