Abstract CT198: A first-in-human study evaluating safety, tolerability and efficacy of TEV-56278, as monotherapy and in combination with pembrolizumab in participants with locally advanced or metastatic solid tumors
Bibliographic record
Abstract
Abstract Background: Direct immune stimulation using cytokines, including interleukin-2 (IL-2), drives immune-mediated cytotoxic cancer responses. Toxicity of high-dose IL-2 limits its activity and clinical utility. Preclinical studies show that targeting IL-2 to specific cell subsets substantially increases its therapeutic index. In multiple cancers, tumor-infiltrating T-cells display higher levels of programmed cell death protein (PD-1) relative to circulating and tissue-resident T-cells, making PD-1 a target for selective delivery of IL-2. TEV-56278 is a human antibody-cytokine fusion protein comprised of an antibody targeting PD-1 and attenuated IL-2. TEV-56278 is designed to deliver IL-2 selectively to PD-1+ T cells, thus amplifying anti-tumor T-cell activity while minimizing off-target systemic toxicities. Furthermore, its binding to PD-1 receptors does not block ligand binding and does not compete for binding with known PD1-blocking antibodies, allowing for combination use. Here, we describe a phase 1a/1b trial design evaluating TEV-56278 as monotherapy and in combination with pembrolizumab. Methods: This multicenter, open-label, Phase 1, first-in-human, dose-escalation, dose-expansion study is being conducted in 3 parts. Patients >18 years of age with various locally advanced or metastatic solid tumors who have progressed on or were intolerant to standard of care therapies and resistant to anti-PD-(L)1 treatment will be included. The primary objective of dose escalation is to assess safety, tolerability and determine the recommended Phase 2 dose (RP2D) of TEV-56278 alone and in combination with pembrolizumab. Secondary objectives include assessment of pharmacokinetics (PK) and anti-tumor activity. Determination of the maximum tolerated dose will be based on a Bayesian optimal interval (BOIN) design. Additional pharmacodynamic and biomarker data, including biomarkers of IL-2 signaling and activation of PD-1+ T cells, will be collected during backfill of monotherapy dose cohort(s). After determination of the monotherapy RP2D, 2 cohorts of patients with locally advanced or metastatic primary and secondary resistant melanoma (A&B) and 2 cohorts of primary and secondary resistant non-small cell lung cancer (NSCLC; [C&D]) will be accrued to evaluate the primary objective of anti-tumor activity. The Simon two-stage admissible design will be used for Cohort B (RP2D and a dose Citation Format: Jason John Luke, Lillian L. Siu, Mario Sznol, Yael Shalit, Jerry Weaver, Samhita Chakraborty. A first-in-human study evaluating safety, tolerability and efficacy of TEV-56278, as monotherapy and in combination with pembrolizumab in participants with locally advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT198.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 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".