A phase IIb, open-label, single-arm study of zanidatamab (ZW25) monotherapy in subjects with advanced or metastatic HER2-amplified biliary tract cancers.
Bibliographic record
Abstract
TPS352 Background: Advanced biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CC), have a poor prognosis. Zanidatamab (ZW25) is a novel bispecific antibody that targets HER2 domains ECD2 and ECD4, resulting in increased antibody binding density and improved receptor internalization and downregulation relative to trastuzumab. In an ongoing phase I trial (ZWI-ZW25-101; NCT02892123), single-agent zanidatamab was well tolerated and showed promising anti-tumor activity across HER2-expressing solid tumors, including BTCs. These results formed the basis for a phase IIb study of zanidatamab in patients with BTC. Methods: Study ZWI-ZW25-203 (NCT04466891) is a global, multicenter, open-label, single-arm, phase IIb trial designed to evaluate the anti-tumor activity of zanidatamab monotherapy in patients with HER2-amplified, inoperable and advanced or metastatic BTCs, including GBC and CC. Patients must have received at least 1 prior gemcitabine-containing systemic chemotherapy regimen for advanced disease and have experienced disease progression after (or developed intolerance to) their most recent prior therapy. New or archival tumor tissue is required from all patients for HER2 amplification and protein expression testing at a central lab using in situ hybridization (ISH) and immunohistochemistry (IHC) assays. Approximately 100 patients with HER2 amplification by ISH will be enrolled. Zanidatamab 20 mg/kg will be administered intravenously every 2 weeks until one of the treatment discontinuation criteria is met. The primary endpoint of the study is the confirmed objective response rate (ORR) by independent central review per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Secondary endpoints include duration of response (DOR), proportion of patients with DOR ≥ 16 weeks, disease control rate, progression-free survival, overall survival, safety, quality of life, and disease-related pain. The safety and tolerability of zanidatamab will be assessed by recording the frequency and severity of adverse events, serious adverse events, and laboratory abnormalities, as well as the frequency of zanidatamab dose modifications. The study is currently open for enrollment. Clinical trial information: NCT04466891.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".