Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

A Phase 1 (Ph1) Study of the OX40 Agonist, BGB-A445, With or Without Tislelizumab, an Anti-PD-1 Monoclonal Antibody (mAb), in Patients With Advanced Solid Tumors (#191)

Jayesh Desai 1 , Diwakar Davar 2 , Sanjeev Deva 3 , Bo Gao 4 , Tianshu Liu 5 , Marco Matos 6 7 8 9 , Tarek Meniawy 10 , Ken J O'Byrne 11 , Meili Sun 12 , Mark Voskoboynik 13 , Kunyu Yang 14 , Xinmin Yu 15 , Xin Chen 16 , Yan Dong 17 , Hugh Giovinazzo 18 , Shiangjiin Leaw 19 , Deepa Patel 16 , Tahmina Rahman 18 , Yanjie Wu 19 , Daphne Day 20 21
  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  2. UPMC Hillman Cancer Center, Pittsburgh, PA, USA
  3. Auckland Cancer Trials Centre, Auckland City Hospital/University of Auckland, Auckland, New Zealand
  4. Blacktown Cancer and Haematology Centre, Blacktown Hospital, Blacktown, NSW, Australia
  5. Affiliated Zhongshan Hospital of Fudan University, Shanghai, China
  6. Pindara Private Hospital, Benowa, QLD, Australia
  7. Medical Oncology Group of Australia, Sydney, NSW, Australia
  8. Australian Medical Council, Canberra, ACT, Australia
  9. Medical Board of Queensland, Brisbane, QLD, Australia
  10. Linear Cancer Research and University of Western Australia, Nedlands, WA, Australia
  11. Princess Alexandra Hospital and Queensland University of Technology, Brisbane, QLD, Australia
  12. Jinan Central Hospital, Shandong University, Central Hospital Affiliated to Shandong First Medical University, Shandong, China
  13. Nucleus Network and Monash University, Melbourne, VIC, Australia
  14. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  15. Zhejiang Cancer Hospital, Hangzhou, China
  16. BeiGene USA, Inc., Ridgefield Park, NJ, USA
  17. BeiGene USA, Inc., Cambridge, MA, USA
  18. BeiGene USA, Inc., San Mateo, CA, USA
  19. BeiGene (Shanghai) Co., Ltd., Shanghai, China
  20. Department of Medical Oncology, Monash Health, Melbourne, VIC, Australia
  21. Faculty of Medicine, Monash University, Melbourne, VIC, Australia

Background: OX40 is an immune costimulatory receptor, expressed on activated CD4+/CD8+ T cells, which promotes T-cell proliferation/survival in the tumor microenvironment. BGB-A445, a novel mAb OX40 agonist, does not compete with endogenous OX40 ligand-binding. In preclinical studies, BGB-A445 demonstrated antitumor activity as monotherapy ± anti-PD-1 mAb. We report data from the ongoing dose-escalation part of a multicenter, ph1 dose-escalation/expansion study (NCT04215978) of BGB-A445 ± tislelizumab in patients with advanced solid tumors.

 

Methods: Eligible patients were enrolled into 7 dose-escalation cohorts of BGB-A445 IV as monotherapy (Part A) or 5 dose levels of BGB-A445 IV + tislelizumab 200 mg IV (Part B) on Day 1 of 21-day cycles. Dose-escalation was guided by a Bayesian (mTPI-2) approach. Endpoints: safety/tolerability, pharmacokinetics (PK), preliminary antitumor activity (RECIST v1.1).

 

Results: As of August 31, 2022, 59 patients enrolled in Part A and 32 in Part B. In Parts A and B, Grade ≥3 treatment-emergent AEs (TEAEs) were reported in 24 (41%) and 17 (53%) patients, respectively; the most reported (≥3 reported) were diarrhea, nausea, and abdominal pain. Serious TEAEs were reported in 23 (39%) patients in Part A and 16 (50%) in Part B. Treatment-related AEs leading to treatment discontinuation occurred in 1 patient (Part A). No patients reported Grade ≥3 imAEs in Part A versus 1 patient in Part B. No DLTs were observed. In the efficacy-evaluable population (Part A, n=50; Part B, n=30), PR was observed in 2 (4%) patients (unconfirmed) and 7 (23%) patients (confirmed), SD in 18 (36%) and 13 (43%) patients (confirmed), and PD in 26 (52%) and 8 (27%) patients, respectively.

 

Conclusions: BGB-A445 ± tislelizumab was well-tolerated across all doses in patients with advanced solid tumors and demonstrated preliminary antitumor activity. The dose-expansion part is ongoing in patients with NSCLC and HNSCC.