A phase 1 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 tumors, including gastrointestinal (GI) cancers.
Bibliographic record
Abstract
TPS847 Background: B7-H3 is an immune checkpoint protein overexpressed in multiple solid tumors 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 antitumor activity in patients of Asian origin with advanced solid tumors (NCT05276609; NCT05830123). The current study will evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of GSK’227 in patients with solid tumors, including GI cancers, in a global population. Methods: This two-part (dose-escalation [1a] and expansion [1b]) global, open-label, Phase I study (NCT06551142) will enroll ~260 patients, with enrollment currently ongoing. Key eligibility includes: aged ≥18 years, histologically confirmed advanced solid tumors, including those with colorectal cancer, esophageal squamous cell carcinoma, and pancreatic cancer, with measurable disease per Response Evaluation Criteria in Solid Tumors 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 (GI and other solid tumors 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. This abstract was previously submitted to the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2024 and is submitted on behalf of the original authors with their permission. Funding: GSK (Study 223054). Medical writing support was provided by Avalere Health, funded by GSK. Clinical trial information: NCT05830123 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.004 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".