Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2021

Safety/Tolerability and Preliminary Antitumour Activity of Sitravatinib Plus Tislelizumab in Patients With Advanced Platinum-Resistant Ovarian Cancer (PROC) (#18)

Jeff Goh 1 , Jermaine Coward 1 , Bo Gao 2 , Ines Pires da Silva 3 , Mark Voskoboynik 4 5 , Daphne Day 6 , Amy Louise Body 6 , Hui K. Gan 7 , Cheng Chen 8 , Xiao Xiang 8 , Cong Fei 8 , Liu Yang 8 , Michael Millward 9 10
  1. Icon Cancer Centre, Brisbane, Australia
  2. Blacktown Cancer and Haematology Centre, Blacktown, NSW, Australia
  3. Blacktown and Westmead Hospitals, Sydney, NSW, Australia
  4. Nucleus Network, Melbourne, VIC, Australia
  5. Central Clinical School, Monash University, Melbourne, VIC, Australia
  6. Monash Health and Monash University, Melbourne, VIC, Australia
  7. Austin Health, Heidelberg, VIC, Australia
  8. BeiGene (Beijing) Co., Ltd., Beijing, China
  9. Linear Clinical Research, Nedlands, WA, Australia
  10. University of Western Australia, Nedlands, WA, Australia

Aims: Sitravatinib, a spectrum-selective tyrosine kinase inhibitor targeting TAM receptors (Tyro3/Axl/MerTK) and VEGFR2, demonstrated antitumour and immune modulatory activity. Tislelizumab, an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages and abrogate antibody-dependent phagocytosis, showed clinical activity in advanced solid tumours. We report results from the PROC cohort of an ongoing multicohort phase 1b study (BGB-900-103; NCT03666143) assessing safety/tolerability and preliminary antitumour activity of sitravatinib+tislelizumab.

Methods: Anti-PD-(L)1 antibody–naïve patients with histologically confirmed advanced PROC (disease progression <6 months after last platinum treatment), but not platinum-refractory disease, were eligible. Patients received oral sitravatinib 120 mg QD plus intravenous tislelizumab 200 mg Q3W. The primary endpoint was safety/tolerability; key secondary and exploratory endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). PD-L1 (Ventana SP263) and plasma VEGF/serum CXCL10 assessments were retrospective.

Results: As of October 13, 2020, 60 PROC patients (median age, 64 years; median of four prior regimens) were enrolled; 13 (22%) remained on treatment. Median follow-up was 6.0 months. Treatment-emergent adverse events (TEAEs) of any grade/grade ≥3 occurred in 97%/68% of patients; TEAEs led to sitravatinib dose reduction in 50% of patients. Hypertension (18%) and abdominal pain (12%) were the most common grade ≥3 TEAEs. Four fatal AEs were deemed unrelated to treatment. Among 53 evaluable patients, ORR was 26% (95% CI, 15.3-40.3; partial response, n=14); DCR was 77% (95% CI, 63.8-87.7). Median duration of response was 4.7 months (95% CI, 2.83-NE). There was no clear association between PD-L1 expression and clinical response; plasma VEGF and serum CXCL10 increased after treatment (P<0.0001 for both). Median PFS was 4.1 months (95% CI, 4.0-5.1); preliminary median OS was 12.9 months (95% CI, 6.3-17.2).

Conclusions: Sitravatinib plus tislelizumab was manageable with preliminary antitumour activity in patients with advanced PROC; further investigation is warranted.