This is a multi-cohort, phase II trial to evaluate the safety and preliminary antitumor activity of 70 mg (cohort A) or 100 mg (cohort B) sitravatinib QD plus tislelizumab in pts with locally recurrent or metastatic TNBC, and their combination with nab-paclitaxel in untreated locally recurrent inoperable or metastatic TNBC pts (cohort C). The preliminary result of cohort A has been reported with ORR of 38.1% (Lei Fan. JCO 2022 40:16_suppl). This analysis aims to report the updated analysis in cohort A and the interim results in cohort B.
Pts with locally recurrent or metastatic TNBC were included and received 70 mg (cohort A) or 100 mg (cohort B) sitravatinib QD PO and 200 mg tislelizumab IV Q3W until disease progression or intolerable toxicity. The primary endpoints included ORR (cohort A and B) and rate of grade ≥3 treatment-related adverse events (TRAEs) (cohort B). Secondary endpoints included DCR, PFS, and safety/tolerability. Updated analysis was provided for cohort A (Simon's 2 stage design). A Bayesian optimal phase II design with one interim analysis (on the first 20 pts out of the total 40 efficacy evaluable pts) was employed for cohort B to monitor both efficacy and safety primary endpoints simultaneously. The stopping boundary of interim analysis was the number of pts with ORR ≤1 or with grade ≥3 TRAEs ≥13.
The data cutoff date of this analysis is 29 July 2022. In cohort A, with the median follow up of 10.7 months, the median PFS was 9.7 (95% CI: 2.8, 12.5) months among 21 efficacy evaluable pts. The rate of grade ≥3 TRAEs was 33.3% (7/21). In cohort B, among the first 20 efficacy evaluable pts with the median follow up of 4.1 months, 9 (45.0% [95% CI: 23.8%-67.9%]) pts were with confirmed ORR and 4 (20%) pts experienced grade ≥3 TRAEs, which met the interim goal. DCR was 80.0% (95% CI: 56.3%-94.27%). At the data cutoff, cohort B achieved the predefined enrollment target.
Sitravatinib combined with tislelizumab demonstrated clinically meaningful anti-tumor activity and had a manageable safety profile in the targeted pts population.
NCT04734262.
The authors.
BeiGene (Beijing) Co., Ltd.
All authors have declared no conflicts of interest.