Abstract CT104: Results from a phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab in patients with previously treated advanced solid tumors
Bibliographic record
Abstract
Abstract Background: In the dose escalation phase of a first-in-human phase 1 study (NCT03564691), the anti-ILT4 IgG4 monoclonal antibody MK-4830 + pembrolizumab (pembro) had a manageable safety profile and demonstrated promising antitumor activity in patients (pts) with previously treated advanced solid tumors, including those with PD on immunotherapy. Here, we present safety, efficacy, and biomarker analyses for MK-4830 + pembro for the previously treated pancreatic adenocarcinoma, glioblastoma, head and neck squamous cell carcinoma (HNSCC), and gastric cancer cohorts of the expansion phase. Methods: Eligible pts were aged ≥18 y with metastatic pancreatic adenocarcinoma and 1-3 lines of prior therapy (cohort A), unresectable glioblastoma and 1 prior line of therapy (cohort B), recurrent or metastatic HNSCC that progressed on a platinum-based chemotherapy and PD-(L)1 inhibitor (cohort C), or recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma that progressed on ≥2 prior chemotherapy regimens (cohort I). Pts in cohorts A, B, and I had not previously received a PD-(L)1 inhibitor. All pts received MK-4830 800 mg + pembro 200 mg Q3W for 35 cycles or until PD, unacceptable toxicity, or study withdrawal. Primary objectives were to evaluate safety and ORR per RECIST v1.1 (cohorts A, C, and I) or Response Assessment in Neuro-Oncology (RANO) criteria (cohort B) by investigator assessment. Exploratory objectives included evaluating DOR and PFS per RECIST v1.1 (cohorts A, C, and I) or RANO criteria (cohort B) by investigator assessment. Results: At data cut-off (September 27, 2023), 33 pts were enrolled and received treatment in cohort A, 20 pts in cohort B, 35 pts in cohort C, and 35 pts in cohort I. Median follow-up duration was 38.4 mo (range, 35.5-39.9) in cohort A, 34.1 mo (32.3-36.2) in cohort B, 37.5 mo (33.4-42.1) in cohort C, and 29.5 mo (22.3-36.4) in cohort I. Treatment-related adverse events (TRAEs) occurred in 15 pts (45%) in cohort A, 13 pts (65%) in cohort B, 19 pts (54%) in cohort C, and 16 pts (46%) in cohort I; grade 3 or 4 TRAEs occurred in 3 pts (9%), 0 pts, 2 pts (6%), and 4 pts (11%), respectively. No deaths due to TRAEs occurred. ORR was 6% (95% CI, 1-20) in cohort A, 5% (0-25) in cohort B, 0% (0-10) in cohort C, and 20% (8-37) in cohort I. Median DOR was 14.3 mo (range, 14.0-14.7) in cohort A, 7.4 mo (7.4-7.4) in cohort B, and 9.6 mo (3.0-27.6+) in cohort I. Median PFS was 1.9 mo (95% CI, 1.6-2.0) in cohort A, 1.2 mo (1.1-1.4) in cohort B, 2.2 mo (1.9-4.1) in cohort C, and 1.4 mo (1.3-3.0) in cohort I. Conclusions: In pts with select previously treated advanced or metastatic solid tumors, MK-4830 + pembro had a manageable AE profile but no significant antitumor activity beyond that historically observed with pembro monotherapy. Other treatment options must be explored for these difficult-to-treat tumors. Citation Format: Lillian L. Siu, Marta Gil-Martin, Byoung Chul Cho, Ruth Perets, John Hilton, Ravit Geva, Iwona Lugowska, Martin Gutierrez, Marcelo Bonomi, Rafal Dziadziuszko, Drew Rasco, Eytan Ben-Ami, Cristina P. Rodriguez, Shabana Siddiqi, Nicole Myer, Leah Suttner, Douglas Wilson, Omobolaji O. Akala, Maria de Miguel. Results from a phase 1 study of the anti-immunoglobulin-like transcript 4 (ILT4) monoclonal antibody MK-4830 plus pembrolizumab in patients with previously treated advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT104.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 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 | 0.001 |
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".