Abstract 1284P
Background
Patients with metastatic non-small cell lung cancer (NSCLC) who are refractory/resistant (R/R) to anti-PD-(L)1 therapies have limited treatment options. Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM and VEGFR2 receptors, which can reduce the number of myeloid-derived suppressor cells, regulatory T cells, and increase the ratio of M1/M2 polarized macrophages, potentially augmenting antitumor immune responses. Tislelizumab, is an anti-PD-1 antibody engineered to minimize binding to FcgR on macrophages to abrogate antibody-dependent phagocytosis, a potential mechanism of resistance. This phase Ib study assessed safety/tolerability and antitumor activity of sitravatinib + tislelizumab in solid tumors (NCT03666143). We report results from NSCLC cohorts.
Methods
Eligible patients had metastatic non-squamous (NSQ) or squamous (SQ) NSCLC with radiographic disease progression on/after anti-PD-(L)1 therapy as their most recent treatment. Patients with EGFR/BRAF mutations or ALK/ROS1 rearrangements were ineligible. Treatment included sitravatinib 120 mg orally QD and tislelizumab 200 mg IV Q3W. The primary endpoint was safety and tolerability. Key secondary endpoints included investigator-assessed objective response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS).
Results
As of 13 Oct 2020, 47 patients with NSQ (n=24) and SQ (n=23) NSCLC were enrolled with a median study follow-up of 7.8 months (range: 0.4–18.1). Median age was 60 years (range: 25–79) and 72% of patients had ≥2 lines of prior therapies. All patients had a treatment-emergent adverse event (TEAE); 68% had a grade ≥3 TEAE (most common: hypertension, 19%). Confirmed ORR was 14% (95% CI: 5.2–27.4) and DCR was 86% (95% CI: 72.7–94.8). Median DoR was 6.9 months (95% CI: 3.1–NE). Median PFS was 5.2 months (95% CI: 4.1–5.9). There was no association between PD-L1 expression and clinical response.
Conclusions
Sitravatinib plus tislelizumab demonstrated a manageable safety profile and promising antitumor activity in patients with PD-(L)1 antibody-pretreated NSCLC. Further investigation of this combination in these pts is warranted.
Clinical trial identification
NCT03666143.
Editorial acknowledgement
Writing and editorial assistance was provided by Stephan Lindsey, PhD and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago, IL), and funded by the study sponsor. Editorial support (in the form of editorial alignment with congress guidance) was provided by Louise Oakes, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by BeiGene, Ltd.
Legal entity responsible for the study
BeiGene, Ltd.
Funding
BeiGene, Ltd.
Disclosure
D. Day: Non-Financial Interests, Principal Investigator: Harbour Biomed. A.L. Body: Financial Interests, Institutional, Principal Investigator: Beigene, Bristol Myers Squibb. C. Chen: Financial Interests, Full or part-time Employment: BeiGene, Ltd.; Financial Interests, Stocks/Shares: BeiGene, Ltd. X. Xiang: Financial Interests, Full or part-time Employment: BeiGene, Ltd.; Financial Interests, Stocks/Shares: BeiGene, Ltd. C. Fei: Financial Interests, Full or part-time Employment: BeiGene, Ltd. L. Yang: Financial Interests, Full or part-time Employment: BeiGene, Ltd.; Financial Interests, Stocks/Shares: BeiGene, Ltd. Y. Wu: Non-Financial Interests, Sponsor/Funding: AstraZeneca, Boehringer Ingelheim, BMS, Hengrui, Pfizer, Roche; Non-Financial Interests, Advisory Role: AstraZeneca, Boehringer Ingelheim, Novartis, Merck, MSD, Roche, Takeda; Financial Interests, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Hengrui, MSD, Pfizer, Roche, Sanofi. All other authors have declared no conflicts of interest.