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).

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