Abstract 1280P
Background
Patients (pts) with advanced NSCLC often develop progressive disease, with limited treatments for pts who are heavily pretreated with anti-PD-(L)1 antibodies and/or chemotherapy. 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 increases the ratio of M1/M2 polarized macrophages, potentially augmenting antitumor 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
Pts had confirmed metastatic nonsquamous (NSQ) or squamous (SQ) NSCLC treated with 1–3 lines of prior systemic therapy with/without an anti-PD-(L)1 inhibitor. Pts with EGFR/ BRAF mutations or ALK/ROS1 rearrangements were ineligible. Sitravatinib was given 120 mg orally QD and tislelizumab 200 mg IV Q3W. The primary endpoint was safety/tolerability. Secondary endpoints were objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression-free survival (PFS).
Results
On 13 Oct 2020, 75 pts (NSQ, n=46; SQ, n=29) were treated; 47 pts were refractory/resistant (R/R) to PD-(L)1 therapy and 28 pts were PD-(L)1 naïve. Median age was 60 yrs (range: 25–79). Median study follow-up was 10.1 mo (range: 0.4–18.8). All pts had a treatment-emergent adverse event (TEAE); 73% of pts had a Grade ≥3 TEAE (most common: hypertension [n=12]). Confirmed ORR was 17% (95% CI: 9.1–27.7); DCR was 85% (95% CI: 74.0–92.0). Median DoR was 7.0 mo (95% CI: 2.9–not estimable). Median PFS was 5.5 mo (95% CI: 4.1–7.0). There was a trend toward higher ORR in pts with PD-L1 IC expression ≥10%. In R/R pts confirmed ORR was 14% (95% CI: 5.2–27.4).
Conclusions
Sitravatinib + tislelizumab had a manageable safety profile and demonstrated preliminary antitumor activity in pts with NSQ or SQ NSCLC who were pretreated or naïve to PD-(L)1 treatment. Further investigation 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.