{Reference Type}: Journal Article
{Title}: Tislelizumab in previously treated, locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors.
{Author}: Li J;Xu Y;Zang A;Gao Y;Gao Q;Zhang Y;Wang D;Xu J;Yuan Y;Jiang H;Ying J;Shi C;Deng Y;Wang J;Liu T;Huang Y;Qian X;Pan Y;Cheng Y;Hu S;Wang J;Shi M;Wang K;Hu H;Shen L;
{Journal}: Chin J Cancer Res
{Volume}: 36
{Issue}: 3
{Year}: 2024 Jun 30
{Factor}: 4.026
{DOI}: 10.21147/j.issn.1000-9604.2024.03.03
{Abstract}: <B>UNASSIGNED: </B>The open-label, phase II RATIONALE-209 study evaluated tislelizumab (anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) tumors.<BR><B>UNASSIGNED: </B>Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate (ORR; primary endpoint), duration of response (DoR), and progression-free survival (PFS) were assessed by independent review committee (Response Evaluation Criteria in Solid Tumors v1.1).<BR><B>UNASSIGNED: </B>Eighty patients were enrolled and treated; 75 (93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease (n=79; 98.8%). At primary analysis (data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval (95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal (n=46): 39.1% (95% CI, 25.1-54.6); gastric/gastroesophageal junction (n=9): 55.6% (95% CI, 21.2-86.3); others (n=20): 60.0% (95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five (6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up (data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.<BR><B>UNASSIGNED: </B>Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.