A phase 1 study of the OX40 agonist BGB-A445, with or without tislelizumab, an anti-PD-1 monoclonal antibody, in patients with advanced NSCLC, HNSCC, or NPC.

Abstract

2525 Background: BGB-A445 is a monoclonal antibody OX40 agonist that does not compete with the natural OX40 ligand, reducing the likelihood of a hook effect and distinguishing it from other OX40-targeting therapies. Here, we present results from the dose expansion portion of a ph 1, open-label, dose escalation/expansion trial of BGB-A445 in pts with advanced solid tumors (NCT04215978). Ph 1a results were previously presented (Desai et al . J Clin Oncol. 2023). Methods: Previously treated pts with NSCLC (Part A1), HNSCC (Part A2), or NSCLC with PD-L1 ≥50% (Part C) received BGB-A445 monotherapy, while pts with treatment-naïve recurrent/metastatic NPC (Part B) received BGB-A445 combined with tislelizumab and chemotherapy. Primary endpoints included ORR per investigator (RECIST v1.1); secondary endpoints were to assess PFS, DOR and DCR, safety/tolerability, PK, and host immunogenicity. Results: As of Sep 25, 2024, 54 pts were enrolled in Part A1, 19 in Part A2, 12 in Part B, and 7 in Part C. In the efficacy evaluable analysis set, ORR was 0% in Parts A1, A2, and C, and 70% (7/10; all confirmed PRs, one unconfirmed CR) in Part B. In Parts A1, A2, B, and C, confirmed DCR was 49.0%, 33.3%, 100.0%, and 57.1%, respectively. TEAEs occurred in the majority of pts (Table). The most common treatment-related TEAEs were pyrexia (10.0% [8/80]), chills (5.0% [4/80]), and anemia (5.0% [4/80]) in the monotherapy cohorts, and anemia (75.0% [9/12]), decreased WBC (66.7% [8/12]), decreased neutrophils, and decreased platelets (58.3% [7/12], each) in the combination cohort. Treatment-related serious TEAEs occurred in 2.5% (2/80; pyrexia and asthenia in a single pt each) of pts in the monotherapy cohorts and 8.3% (1/12; febrile neutropenia) in the combination cohort. There were no BGB-A445 or tislelizumab-related TEAEs leading to treatment discontinuation or death. The most common imAE was rash (2.5% [2/80] in the monotherapy cohort; 33.3% [4/12] in the combination cohort). No Gr ≥3 imAEs or IRRs were reported. Conclusions: BGB-A445 alone or in combination with tislelizumab and chemotherapy was generally well tolerated across all doses in pts with advanced NSCLC, HNSCC, and NPC, and showed preliminary antitumor activity. Clinical trial information: NCT04215978 . Safety. Part A1NSCLC(N=54) Part A2HNSCC(N=19) Part BNPC(N=12) Part CNSCLC and PD-L1 ≥50%(N=7) Any treatment-emergent AE 47 (87.0) 16 (84.2) 12 (100.0) 7 (100.0) Gr ≥3 17 (31.5) 5 (26.3) 11 (91.7) 3 (42.9) Serious 21 (38.9) 4 (21.1) 2 (16.7) 4 (57.1) Leading to death 4 (7.4) 2 (10.5) 0 (0) 0 (0) Leading to treatment discontinuation 8 (14.8) 3 (15.8) 2 (16.7) 0 (0) Any treatment-related treatment-emergent AE 28 (51.9) 7 (36.8) 12 (100.0) 3 (42.9) Gr ≥3 1 (1.9) 0 (0) 11 (91.7) 0 (0) Any immune-mediated AE 6 (11.1) 1 (5.3) 6 (50.0) 1 (14.3) Infusion-related reactions 6 (11.1) 3 (15.8) 3 (25.0) 1 (14.3) Pts with multiple adverse events (AEs) are counted once. All AEs are listed as n (%).