Background: The Phase 1/2, dose escalation/expansion study evaluates NGM707, a dual anti-ILT2/ILT4 humanized monoclonal antibody, as monotherapy or in combination with pembrolizumab in patients (pt) with advanced solid tumors. Methods: We enrolled pt with locally advanced or metastatic solid tumors into dose-escalating cohorts of 6-1800 mg NGM707 monotherapy and 200-1800 mg NGM707 combined with 200 mg pembrolizumab, administered Q3W IV. Primary aim was to assess safety/tolerability and dosing of expansion cohorts. Secondary/exploratory objectives included pharmacokinetics, biomarkers, and preliminary antitumor activity per RECIST v1.1. Results: As of November 6, 2023, we treated 82 pt with NGM707 monotherapy or combination at dose levels up to 1800 mg; five pt crossed over from monotherapy to combination. Primary tumor types included colorectal, NSCLC, gastric, pancreatic, and melanoma. Median age 59 yrs [28-85]; ECOG PS 0 (18.3%), 1 (81.7%). Pt received a median of 4 prior therapies (range 1-16) and 91.5% had metastatic disease. Fifty percent of the pt were pre-treated with anti-PD(L)1. Peripheral RO was dose-dependent, with NGM707 doses ≥200 mg maintaining full ILT2 and ILT4 RO. PK was typical for monoclonal antibodies, with a half-life of 12.8 days. Paired tumor biopsies showed evidence of myeloid and T cell activation. Treatment(tx)-related adverse events (TEAEs) any grade/grade ≥3 occurred in 46.3%/4.8% of pt in the monotherapy and 41.3%/4.4% of pt in the combination. Fatigue (12.2%), arthralgia (9.8%), nausea (9.8%) were reported in monotherapy; fatigue (17.4%), diarrhea (6.5%) were reported in combination. One dose-limiting toxicity (DLT; pneumonitis) occurred in monotherapy and no DLTs in combination. MTD was not reached for both tx; MAD was 1800 mg NGM707. Of 35 response-evaluable monotherapy pt, best overall responses (BOR) were one confirmed PR in pt with melanoma, SD (n=9) and non-CR/non-PD (n=1), leading to DCR ~31%. Eight pt had reduced target lesion (TL) size with maximum reduction of 71%. Of 37 response-evaluable pt in combination, the BOR to date are PR (confirmed; n=4), and SD (n=12), representing DCR ~43%. Nine pt had reduced TL size with a maximum reduction of 100%. Of the 4 pt who had PR, 3 pt were pre-treated with anti-PD(L)1. Two pt with MSS CRC achieved PR, one of them with liver/adrenal TL reduction allowing surgical resection of all residual disease with pCR; ctDNA was not detected. Durable response in this pt led to PFS of 11 months prior to the surgery and ongoing DFS post-surgery. Conclusions: NGM707 as monotherapy and in combination with pembrolizumab was safe and well tolerated at all dose levels. In heavily pretreated advanced and metastatic solid tumor malignancies, we observed early efficacy and biomarker signals, including in tumors considered unresponsive to anti-PD(L)1. These results support further evaluation of NGM707. Clinical trial information: NCT04913337.