Phase 1 study of the anti–immunoglobulin-like transcript 3 (ILT3) monoclonal antibody (mAb) MK-0482 + pembrolizumab (pembro) + paclitaxel for previously untreated advanced triple negative breast cancer (TNBC).
Bibliographic record
Abstract
e13135 Background: First-line treatment for advanced TNBC with PD-L1 CPS ≥10 is chemotherapy plus pembro. ILT3 is an inhibitory receptor expressed on monocytic myeloid cells. High ILT3 expression is associated with immune tolerance and suppression of T-cell function. MK-0482 is an anti-ILT3 mAb hypothesized to relieve immunosuppression and improve T-cell function within the tumor microenvironment. Safety and efficacy data from a dose expansion cohort of the first-in-human, phase 1 MK-0482-001 study (NCT03918278) evaluating MK-0482 in combination with pembro + paclitaxel in participants (pts) with previously untreated advanced TNBC are presented here. Methods: Pts aged ≥18 y with recurrent inoperable or metastatic TNBC with centrally confirmed PD-L1 CPS ≥1, no prior systemic therapy for metastatic disease, and ECOG PS 0 or 1 received MK-0482 750 mg IV + pembro 200 mg IV Q3W for up to 35 cycles + paclitaxel 90 mg/m 2 IV on days 1, 8, and 15 Q4W until PD or discontinuation. The primary end point was safety. Secondary end points included ORR and DOR per RECIST v1.1 by investigator assessment. Exploratory end points included PFS per RECIST v1.1 by investigator assessment. Results: Of 45 pts enrolled and who received ≥1 dose of study treatment, 38 (84%) discontinued treatment at data cutoff (Oct 28, 2024), most commonly because of PD (76%). Median study follow-up was 27.6 mo (range, 23.8-34.0). Median age was 54 y (range, 26-80); 18 pts (40%) had an ECOG PS of 1, 21 (47%) had metastatic disease, 28 (62%) had tumors with CPS ≥1 to <10, and 17 (38%) had tumors with CPS ≥10. Treatment-related AEs occurred in 44 pts (98%); grade 3 or 4 treatment-related AEs occurred in 21 pts (47%), most commonly (≥10%) decreased neutrophil count (22%) and neutropenia (13%). No grade 5 treatment-related AEs occurred. Treatment-related AEs led to discontinuation in 11 pts (24%); 5 (11%) discontinued MK-0482, 3 (7%) discontinued pembro, and 8 (18%) discontinued paclitaxel. Response data are presented in the table. Exploratory biomarker data will be included in the presentation. Conclusions: In pts with advanced TNBC, MK-0482 + pembro + paclitaxel had a manageable safety profile, but showed no difference in efficacy compared to that historically observed with pembro + paclitaxel or gemcitabine-carboplatin. Therefore, further investigation of this combination will not be pursued for advanced TNBC. Clinical trial information: NCT03918278 . Efficacy outcomes. CPS ≥1 to <10n = 28 CPS ≥10n = 17 Total (CPS ≥1)n = 45 Confirmed ORR, % (95% CI) 50 (31-69) 53 (28-77) 51 (36-66) CR, n (%) 1 (4) 2 (12) 3 (7) PR, n (%) 13 (46) 7 (41) 20 (44) SD, n (%) 9 (32) 6 (35) 15 (33) PD, n (%) 4 (14) 2 (12) 6 (13) No assessment, n (%) 1 (4) 0 1 (2) DOR, median (range), months 6.2 (3.5 to 32.5+) 7.5 (4.2 to 30.4+) 6.5 (3.5 to 32.5+) PFS, median (95% CI), months 6.1 (4-8) 7.6 (4-10) 6.2 (5-8) 6/12-month PFS rates, % 54/21 65/24 58/22
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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) | 0.001 | 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) | 0.007 | 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".