Abstract CT265: Phase 1 dose-escalation study of SGN-TGT monotherapy in patients with advanced malignancies
Bibliographic record
Abstract
Abstract Background: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory immune checkpoint receptor expressed on subsets of T-cells and natural killer (NK) cells. TIGIT inhibits T and NK cell function by binding to CD155 and CD112. SEA-TGT is an investigational human, nonfucosylated monoclonal antibody directed against TIGIT, blocking TIGIT's interaction with CD155 and CD112. SGNTGT-001 (NCT04254107) is a phase 1, open-label, multicenter study of SEA-TGT in patients (pts) with advanced malignancies (solid tumors and lymphomas). In this abstract, we present data from the dose-escalation phase (Part A). Methods: Pts received SEA-TGT ranging from 0.01 to 6.0 mg/kg of body weight intravenously every 3 weeks (Q3W). The primary objectives were to evaluate the safety and tolerability of SEA-TGT and identify the maximum tolerated dose (MTD) or the recommended dose and schedule of SEA-TGT. The optimal biological dose was defined using the Clinical Utility Index. Secondary objectives included the evaluation of antitumor activity, pharmacokinetics (PK) and immunogenicity. Antitumor activity was based on Response Evaluation Criteria in Solid Tumors version 1.1 or the Lugano classification criteria with Lymphoma Response to Immunomodulatory Therapy Criteria. Results: From June 12, 2020, to October 5, 2022, 41 pts were enrolled (2, 4, 5, 11, 12, and 7 pts in the 0.01, 0.1, 0.3, 1, 3, and 6 mg/kg cohorts, respectively). Among the 39 pts who were treated 23 pts had solid tumors and 16 had lymphomas. The median number of prior therapies across all cohorts was 5. Treatment emergent adverse events of any grade were reported in 100% of pts, and treatment-related adverse events (TRAEs) of any grade were reported in 69.2%. TRAEs seen in ≥10% of the pts were infusion-related reaction (38.5%), chills (25.6%), pyrexia (17.9%), fatigue (12.8%), maculopapular rash (12.8%), and rash (10.3%). Seven pts (17.9%) reported TRAEs grade ≥3, and rash (5.1%) was the most frequently reported. No grade 4 or 5 TRAEs were reported. One dose-limiting toxicity, pruritic rash, was observed in 1 pt in the 6 mg/kg cohort, and MTD was not exceeded. Based on the PK and pharmacodynamic data, 1 mg/kg Q3W was selected as the optimal biological dose for the expansion cohorts. One partial response was observed in a pt with gastric cancer, and 2 partial metabolic responses were seen in a pt with Hodgkin’s lymphoma and a pt with diffuse large B-cell lymphoma. Conclusions: Overall, clinical data for SEA-TGT from the SGNTGT-001 trial suggest a manageable and tolerable safety profile. Preliminary antitumor activity warrants further clinical evaluation of SEA-TGT. SGNTGT-001 is ongoing and evaluating monotherapy and combination therapies. Citation Format: Elena Garralda Cabanas, Elisa Fontana, Honey Kumar Oberoi, Nataliya V. Uboha, Ecaterina E. Dumbrava, Emiliano Calvo, Giuseppe Curigliano, Diwakar Davar, Bridget K. Keenan, Vincent K. Lam, Sudhir Manda, Amitkuma Mehta, Anna Minchom, Alison Moskowitz, Ravi Paluri, Vincent Ribrag, Donald Richards, Lillian Siu, Paul Swiecicki, Trisha Wise-Draper, Jasmine Zain, Andres Forero-Torres, Ping Xu, Stephen Ansell. Phase 1 dose-escalation study of SGN-TGT monotherapy in patients with advanced malignancies [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 CT265.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 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 | 0.003 |
| 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".