A phase 1 study of BGB-A3055 (anti-CCR8) with or without tislelizumab (anti–PD-1) in patients with solid tumors.

Abstract

2523 Background: BGB-A3055 is a humanized monoclonal antibody targeting C-C motif chemokine receptor 8 (CCR8), a receptor highly expressed on intratumoral regulatory T cells (Tregs). CCR8 overexpression correlates with poor prognosis in certain tumor types. Preclinical studies have shown potent antitumor activity of BGB-A3055 . Here, we present results from a phase 1a dose-escalation trial of BGB-A3055 alone (Part A [A]) or combined with tislelizumab (TIS; Part B [B]) in patients (pts) with advanced or metastatic solid tumors (NCT05935098). Methods: Eligible pts had histologically confirmed advanced or metastatic solid tumors with high prevalence of CCR8 expression. In A, pts received BGB-A3055 (six dose levels) intravenously (IV) every 3 weeks (Q3W). In B, pts received BGB-A3055 (six dose levels) and TIS 200 mg IV Q3W . Primary endpoint was safety; secondary endpoints included preliminary antitumor activity (RECIST v1.1). Results: As of Nov 19, 2025, 98 pts were treated with BGB-A3055 ± TIS (A: n=42; B: n=56). Median (range) study follow-up was 3.94 (0.9-19.0) months in A and 4.67 (0.5-16.8) months in B. Treatment-emergent adverse events (TEAEs) are provided in the Table. The most common BGB-A3055-related TEAEs were neutrophil count decreased (23.8%) in A and pyrexia (23.2%) in B. The most common serious TEAE was immune-mediated enterocolitis (A: 4.8%; B: 7.1%). The most common immune-mediated adverse events (imAEs) were rash, rash maculo-papular, and hypothyroidism in A (7.1% each) and rash maculo-papular in B (17.9%). Dose-limiting toxicities occurred in 1 pt in A (immune-mediated hepatitis) and 3 pts in B (colitis, nephrotic syndrome, and rash maculo-papular in a single pt each). No treatment-related TEAEs leading to death were reported. Maximum tolerated dose was not reached. Unconfirmed objective response rate was 7.5% (95% confidence interval [CI]: 1.6-20.4; 3 partial responses [PRs]) in A and 18.2% (95% CI: 9.1-30.9; 1 complete response and 9 PRs) in B. Disease control rate was 35.0% (95% CI: 20.6-51.7) in A and 56.4% (95% CI: 42.3-69.7) in B. Among the 13 responders, 6 received prior immunotherapies. Robust Treg reduction was observed in peripheral blood and tumor tissue post-treatment, indicating potent on-target pharmacodynamic activity of BGB-A3055. Conclusions: BGB-A3055 ± TIS demonstrated a safety profile consistent with selective CCR8 on-target effects in pts with advanced solid tumors and had preliminary antitumor activity. Clinical trial information: NCT05935098 . Part ABGB-A3055 monotherapy(n=42) Part BBGB-A3055 + TIS(n=56) Any TEAE, n (%) 41 (97.6) 55 (98.2) Grade ≥3 26 (61.9) 47 (83.9) Serious 17 (40.5) 37 (66.1) Leading to death 1 (2.4) 3 (5.4) Leading to treatment discontinuation 9 (21.4) 23 (41.1) Any BGB-A3055-related TEAE, n (%) 35 (83.3) 53 (94.6) Grade ≥3 18 (42.9) 31 (55.4) Serious 5 (11.9) 20 (35.7) Any imAE, n (%) 15 (35.7) 33 (58.9)