Pts with R/M CC have poor prognoses with high unmet clinical needs and few treatment (tx) options. Dual targeting of solid tumors with anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) and anti-PD-1 mAbs enhances antitumor activity in preclinical studies and clinical studies of other tumors. AdvanTIG-202 (NCT04693234) is investigating the efficacy and safety of TIS (anti-PD-1 mAb) ± OCI (humanized Fc-intact IgG1 anti-TIGIT mAb) in pts with R/M CC. Primary analysis results are reported here. Eligible pts with R/M CC had received ≥1 line of chemotherapy and were not amenable to curative tx. In Stage 1, 80 pts were randomized (1:1) to receive 200 mg TIS IV Q3W + 900 mg OCI IV Q3W (Cohort [C]1) or TIS monotherapy (C2) until disease progression, unacceptable toxicity, or withdrawal of consent. In Stage 2, C1 enrolled 98 additional pts. Primary endpoint: ORR per RECIST v1.1 by IRC for C1. Secondary endpoints: DoR, PFS, OS, and safety. As of June 16, 2022, 138 pts were enrolled and treated in C1 (median age 53.0 y); median study follow-up: 7.4 mo. In the safety analysis set (SS), the ORR was 22.5%, with 13 complete responses (CR; Table); 76.8% had a durable response of ≥6 mo. ORR was 26.2% in pts with PD-L1+ tumors (PD-L1 score ≥5%), with 10 CRs. Both analysis sets showed significant improvement in ORR vs historical control ORR of 15% in pts treated with anti-PD-1 therapy (P<0.05). Around 67% of pts experienced ≥1 tx-related adverse event (TRAE). Only 13% of pts experienced ≥grade 3 TRAEs; the most frequently reported were anemia (2%) and rash (1%). With limited enrollment in C2 (n=40), the ORR was 32.5%. Table: 744MOCohort 1Safety analysis seta (n=138)PD-L1 + (n=84)ORR, % (95% CI)22.5 (15.8, 30.3)26.2 (17.2, 36.9)n (%)Complete response Partial response Stable disease Progressive disease Not determined13 (9.4) 18 (13.0) 56 (40.6) 39 (28.3) 12 (8.7)10 (11.9) 12 (14.3) 34 (40.5) 20 (23.8) 8 (9.5)mDoR, mo 95% CINE (5.6, NE)NE (5.6, NE)mPFS, mo 95% CI3.5 (2.6, 4.9)4.2 (2.7, 6.9)mOS, mo 95% CI9.0 (8.1, 10.4)10.4 (8.1, NE)Data cutoff: June 16, 2022. Efficacy assessed by IRC. aPts who received ≥1 dose of any study drug. DoR, duration of response; IRC, independent review committee; m, median; mo, months; NE, not estimable; ORR, objective response rate; OS, overall survival; PFS, progression-free survival. Open table in a new tab . Data cutoff: June 16, 2022. Efficacy assessed by IRC. aPts who received ≥1 dose of any study drug. DoR, duration of response; IRC, independent review committee; m, median; mo, months; NE, not estimable; ORR, objective response rate; OS, overall survival; PFS, progression-free survival. OCI + TIS showed promising antitumor activity and durable responses, regardless of PD-L1 expression, and was well tolerated in pts with previously treated R/M CC.

TIS is an anti-programmed cell death protein 1 monoclonal antibody engineered to minimize FcγR binding. Primary results from this single-arm, multicenter, open-label, phase 2 study (NCT03736889) evaluating TIS in pts with MSI-H/dMMR solid tumors showed a clinically meaningful objective response rate (ORR). Here, we report updated analysis with longer follow-up. Eligible adult participants had previously treated, locally advanced, unresectable/metastatic solid tumors with centrally confirmed MSI-H/dMMR, ≥1 measurable lesion (RECIST v1.1), and an ECOG performance status ≤1. Pts received TIS 200 mg intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was Independent Review Committee (IRC)-assessed ORR (RECIST v1.1). Secondary endpoints included overall survival (OS), IRC-assessed duration of response (DoR), progression-free survival (PFS), and disease control rate, and safety. Of 80 pts enrolled and treated in the study, 75 had measurable disease per IRC at baseline and were included in the efficacy-evaluable population. At data cutoff (Dec 5, 2022), median study follow-up was 28.9 months; minimum follow-up from last patient in to data cutoff was 28.1 months. Efficacy results are shown in the Table. ORR was 49.3%; median DoR, PFS, and OS were not reached. Treatment-emergent adverse events (TEAEs) ≥grade 3 occurred in 48 pts (60.0%); the most common was anemia, occurring in nine pts (11.3%). TEAEs leading to treatment discontinuation occurred in six pts (7.5%). With a minimum of 28.1 months’ follow-up, TIS-treated pts with previously treated MSI-H/dMMR solid tumors demonstrated a higher ORR compared with previous analysis, and durable improvements in DoR, PFS, and OS, with no new safety signals.Table: 1057PTumor Response in the Efficacy-evaluable PopulationAll tumor types (N=75)ORR, n (%)37 (49.3)95% CI37.6, 61.1Best overall response, n (%)Complete response10 (13.3)Partial response27 (36.0)mDoR,a mo (95% CI)NR (NE, NE)24-month DoR rate, % (95% CI)97.0 (80.4, 99.6)mPFS,a mo (95% CI)NR (7.5, NE)24-month PFS rate, % (95% CI)56.7 (44.1, 67.4)mOS, mo (95% CI)NR (33.3, NE)24-month OS rate, % (95% CI)68.6 (56.6, 77.9)aIRC-assessed per RECIST v1.1 OS analysis is based on safety analysis population (N=80). CI, confidence interval; m, median; mo, months; NE, not estimable; NR, not reached. Open table in a new tab