Abstract CT058: TROPION-PanTumor03: Phase 2, multicenter study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients (pts) with advanced/metastatic solid tumors
Bibliographic record
Abstract
Abstract Background: Pts with metastatic epithelial tumors who progress after initial therapy have a poor prognosis; new therapeutic agents could potentially improve outcomes. Trophoblast cell surface protein 2 (TROP2) is a transmembrane glycoprotein that is over-expressed on the cell surface of many epithelial cancers representing a promising target for surface-directed therapeutic modalities. Dato-DXd is an antibody-drug conjugate consisting of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to a highly potent topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. Dato-DXd monotherapy demonstrated encouraging efficacy and safety in pts with lung and breast cancer (TROPION-PanTumor01 study; NCT03401385). Methods: The phase 2, multicenter, open-label TROPION-Pantumor03 study (NCT05489211) is exploring safety and efficacy of Dato-DXd as monotherapy and in combination with various anticancer agents (e.g. durvalumab, AZD5305, nivolumab, bevacizumab, chemotherapies) that may be active in the tumor types being evaluated. TROPION-Pantumor03 is a master trial comprising independent substudies to enable simultaneous evaluation of the recommended phase 2 dose (RP2D), safety, and preliminary efficacy of Dato-DXd across several tumor types and treatment combinations. Pts with endometrial, gastric, metastatic castration-resistant prostate (mCRPC), ovarian, and colorectal (CRC) cancer are being enrolled. Eligible pts: age ≥18 years, histologically/cytologically documented advanced or metastatic disease, ≥1 measurable target lesion (RECIST 1.1) not previously irradiated (mCRPC substudy: non-measurable bone metastatic disease permitted), and adequate bone marrow and organ function. An FFPE tumor sample must be available for all pts. Prospective selection for TROP2 expression is required in pts with CRC; in all other cohorts, TROP2 expression will be analyzed retrospectively. In all monotherapy cohorts, pts will receive Dato-DXd 6 mg/kg IV infusion Q3W; in the combination cohorts, Dato-DXd 4 or 6 mg/kg Q3W, as appropriate for each combination. Pts will receive treatment until disease progression, unacceptable toxicity, or withdrawal. Primary Endpoints: Objective response rate, PSA50 response (mCRPC substudy only), and safety/tolerability. Secondary Endpoints: Progression-free survival, duration of response, disease control rate, best % change in tumor size, pharmacokinetics, and immunogenicity (anti-drug antibodies). Exploratory endpoints incl. overall survival, pt-reported outcomes, and biomarker analysis (incl. TROP2 and PD-L1 expression, tumor mutational profiling, proteomics and ctDNA profiling). Recruitment is ongoing as of Jan 2023. Citation Format: Funda Meric-Bernstam, Yelena Janjigian, Joshua Lang, Kristen K. Ciombor, Isabelle Ray-Coquard, Amit Oza, Kan Yonemori, Ruihua Xu, Jimmy L. Zhao, Srikanth Gajavelli, Justyna Filant, Tina Hovey, Ana Oaknin. TROPION-PanTumor03: Phase 2, multicenter study of datopotamab deruxtecan (Dato-DXd) as monotherapy and in combination with anticancer agents in patients (pts) with advanced/metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT058.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".