BeiGene Presents Clinical Data on Sitravatinib in Combination with Tislelizumab at the AACR Annual Meeting 2021

BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative medicines worldwide, today announced that clinical data on its anti-PD-1 antibody tislelizumab, in combination with the investigational spectrum-selective kinase inhibitor sitravatinib being jointly developed with Mirati Therapeutics, Inc. (Mirati), were presented in two oral presentations at the American Association for Cancer Research (AACR) Annual Meeting 2021. Data presented at the meeting were from two cohorts of a Phase 1b trial (NCT03666143), in patients with unresectable or metastatic melanoma who were refractory or resistant to PD-1/L1 inhibitors and in patients with advanced platinum-resistant ovarian cancer (PROC).

BeiGene has an exclusive collaboration and license agreement with Mirati for the development, manufacturing and commercialization of sitravatinib in Asia (excluding Japan), Australia, and New Zealand.

“From the results presented today, we believe that sitravatinib in combination with tislelizumab could potentially provide clinical benefit to patients with advanced solid tumors, which supports our plan to further evaluate this innovative combination in our ongoing clinical trials. In addition, we are excited about the preliminary antitumor activity observed in patients with PD-1/L1 resistant or refractory melanoma,” commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. “As we continue to follow these patients and complete enrollment in this trial, we are excited to expand our knowledge of this novel combination in the hope that it will lead to a combination therapy that can help more patients around the world in the fight against cancer.”

This open-label, multicohort, Phase 1b trial was designed to evaluate safety/tolerability and preliminary antitumor activity of sitravatinib in combination with tislelizumab in advanced solid tumors. The primary endpoint of the trial was safety/tolerability of the combination; key secondary endpoints include investigator-assessed objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) per RECIST v1.1; overall survival (OS) was also assessed.

Results in Patients with Unresectable or Metastatic Melanoma Refractory or Resistant to PD-1/L1 Inhibitors

“Checkpoint inhibitors have changed the treatment of advanced melanoma, but a significant proportion of patients do not benefit from PD-1 inhibitors due to primary or innate resistance. In this Phase 1b trial, we’re glad to see that the combination of sitravatinib and tislelizumab was generally well-tolerated and demonstrated encouraging preliminary antitumor activity in patients with PD-1/L1 resistant melanoma,” commented Chuanliang Cui, Professor at Beijing Cancer Hospital in China.

At the time of data cutoff on October 13, 2020, a total of 25 patients with unresectable or metastatic melanoma who were refractory or resistant to anti-PD-1/L1 antibodies and had not received other prior immunotherapy had been enrolled in cohort G of the Phase 1b trial, including 12 with cutaneous subtype, seven with acral subtype, and four with mucosal subtype. At the time of data cutoff, 16 patients (64%) remained on study treatment. With a median follow-up time of 5.5 months, results included:

• All 25 patients (100%) experienced at least one treatment-emergent adverse event (TEAE) of any grade, with the most common (≥20%) being increased alanine transaminase (ALT; 76%), increased aspartate aminotransferase (AST; 68%), increased blood cholesterol (56%), hypertriglyceridemia (52%), hypothyroidism (48%), weight decreased (48%), increased blood creatine kinase (BCK; 40%), diarrhea (40%), increased gamma-glutamyltransferase (GGT; 40%), proteinuria (40%), increased blood bilirubin (BB; 36%), abnormal electrocardiogram T wave (36%), hypertension (36%), palmar-plantar erythrodysesthesia syndrome (32%), increased CK-myocardial band isozyme (CK-MB; 28%), hyperuricemia (28%), upper abdominal pain (24%), vomiting (24%), and hypokalemia (20%);
• Twelve patients (48%) experienced at least one Grade ≥3 TEAE, with the most common (≥5%) being hypertension (12%), increased ALT (8%), and increased GGT (8%);
• One patient (4%) experienced a serious TEAE of anal abscess, associated with sitravatinib;
• Treatment discontinuation due to TEAEs occurred in two patients (8%), with one discontinuing tislelizumab due to vaginal hemorrhage (unrelated to tislelizumab) and the other sitravatinib due to increased BCK (related to sitravatinib);
• Dose interruptions and reductions of sitravatinib occurred in 18 patients (72%) and 13 patients (52%), respectively;
• All 25 patients were evaluable for efficacy and the confirmed ORR was 24% (95% CI: 9.4, 45.1), including six partial responses (PRs), and the disease control rate (DCR) was 88% (95% CI: 68.8, 97.5); and
• The media duration of response (