BANTAM-01: A Multicenter, Open-Label, First-in-Human Phase 1 Dose Escalation and Expansion Study of <sup>225</sup> Ac-GPC3 (BAY 3547926) in Patients with Advanced Hepatocellular Carcinoma
Bibliographic record
Abstract
Despite the increasing availability of systemic therapies to treat advanced hepatocellular carcinoma (HCC), the prognosis remains poor. There is therefore an unmet need for targeted therapies with a novel mode of action that are more tolerable and effective than current treatment options. Targeted α-therapies selectively deliver high-energy α-particle–emitting radionuclides to tumor-associated cell surface antigens, inducing difficult-to-repair DNA double-stranded breaks, while limiting damage to surrounding tissue. Elevated expression of the oncofetal cell surface heparan sulfate proteoglycan, glypican-3 (GPC3), is seen in more than 70% of HCCs and is a negative prognostic indicator. BAY 3547926 (225Ac-GPC3) is an 225Ac-labeled antibody–chelator conjugate (ACC) that delivers 225Ac directly to GPC3-expressing cancer cells and is a potential first-in-class targeted α-therapy in advanced HCC. Methods: This multicenter, open-label, nonrandomized first-in-human phase 1 dose escalation and expansion study aims to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of 225Ac-GPC3 ACC, with or without preinjection of the nonradioactive GPC3 ACC, in participants with advanced HCC. The study has 3 parts: dose escalation, dose expansion as monotherapy, and safety run-in and dose expansion in combination with standard of care. Key eligibility criteria include diagnosis of locally advanced or metastatic and/or unresectable HCC, with disease not amenable to, or progressive disease after, curative surgery and/or locoregional therapies. To ensure only participants who are good candidates to benefit from 225Ac-GPC3 ACC enter the study, participants will be prospectively screened to confirm GPC3 membrane expression in a tumor specimen. All participants will receive study treatment on day 1 of a 6-wk cycle; additionally, participants in part 3 will receive standard-of-care treatment at the usual frequency. Participants will receive up to 4 doses of the study intervention, unless withdrawn from the study on disease progression, unacceptable toxicity, or fulfillment of any other withdrawal criteria. Primary endpoints include assessment of the occurrence and severity of treatment-emergent adverse events, recommended dose, objective response rate, disease control rate, duration of response, and progression-free survival. Conclusion: Study recruitment commenced in March 2025, and approximately 148 participants will be enrolled. The study will provide important preliminary insights on the efficacy and safety of 225Ac-GPC3 ACC therapy.
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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) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.003 | 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".