Phase 2 study of tislelizumab monotherapy in previously treated, locally advanced, unresectable or metastatic microsatellite instability-high/mismatch repair-deficient solid tumors: Gynecological cancer subgroup (127)

Objectives: Primary results from this Phase II study (NCT03736889) showed that tislelizumab (TIS), an anti-PD-1 antibody, was generally well tolerated and demonstrated a clinically meaningful improvement in the objective response rate (ORR) in patients (pts) with previously treated, locally advanced, unresectable or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) solid tumors compared with the historical control rate (45.9% vs 10 %, respectively) [1]. Here, we report results from the updated analysis for pts with gynecologic MSI-H/dMMR tumors. Methods: Eligible pts received TIS 200 mg intravenously once every three weeks until disease progression, unacceptable toxicity, or withdrawal. ORR, duration of response (DoR), time to response (TTR), disease control rate (DCR), progression-free survival (PFS) (all assessed by independent committee review per RECIST v1.1), overall survival (OS), and safety were evaluated in pts with gynecologic tumors. Results: At the time of the latest data cut-off (July 8, 2021), 80 pts were enrolled, and 75 pts were included in the efficacy analysis set, of whom 15 had gynecologic tumors (median age: 55 years; range: 41-67 years): 13 had endometrial cancer, one had cervical cancer, and one had ovarian cancer. ORR in pts with gynecologic tumors was 53.3% (95% CI: 26.6-78.7). Three pts had complete responses (all had endometrial cancer), five pts had a partial response (three pts with endometrial cancer, one pt with cervical cancer, and one pt with ovarian cancer), one pt had stable disease (endometrial cancer), and four pts had progressive disease (endometrial cancer). At a median follow-up duration of 17.5 months, me dian OS was not reached; median PFS and median DoR were also not reached. Median TTR was 9.1 weeks, and DCR was 60.0% (95% CI: 32.3-83.7). TIS was generally well tolerated in pts with gynecologic tumors (Table 1); the most common treatment-emergent adverse events were increased alanine aminotransferase (86.7%), increased aspartate aminotransferase (46.7%), decreased white blood cell count (46.7%), and anemia (46.7%). Objectives: Primary results from this Phase II study (NCT03736889) showed that tislelizumab (TIS), an anti-PD-1 antibody, was generally well tolerated and demonstrated a clinically meaningful improvement in the objective response rate (ORR) in patients (pts) with previously treated, locally advanced, unresectable or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) solid tumors compared with the historical control rate (45.9% vs 10 %, respectively) [1]. Here, we report results from the updated analysis for pts with gynecologic MSI-H/dMMR tumors. Methods: Eligible pts received TIS 200 mg intravenously once every three weeks until disease progression, unacceptable toxicity, or withdrawal. ORR, duration of response (DoR), time to response (TTR), disease control rate (DCR), progression-free survival (PFS) (all assessed by independent committee review per RECIST v1.1), overall survival (OS), and safety were evaluated in pts with gynecologic tumors. Results: At the time of the latest data cut-off (July 8, 2021), 80 pts were enrolled, and 75 pts were included in the efficacy analysis set, of whom 15 had gynecologic tumors (median age: 55 years; range: 41-67 years): 13 had endometrial cancer, one had cervical cancer, and one had ovarian cancer. ORR in pts with gynecologic tumors was 53.3% (95% CI: 26.6-78.7). Three pts had complete responses (all had endometrial cancer), five pts had a partial response (three pts with endometrial cancer, one pt with cervical cancer, and one pt with ovarian cancer), one pt had stable disease (endometrial cancer), and four pts had progressive disease (endometrial cancer). At a median follow-up duration of 17.5 months, me dian OS was not reached; median PFS and median DoR were also not reached. Median TTR was 9.1 weeks, and DCR was 60.0% (95% CI: 32.3-83.7). TIS was generally well tolerated in pts with gynecologic tumors (Table 1); the most common treatment-emergent adverse events were increased alanine aminotransferase (86.7%), increased aspartate aminotransferase (46.7%), decreased white blood cell count (46.7%), and anemia (46.7%).