A Phase 1/2 First-Time-in-Human open-label multicenter dose escalation and expansion study of the oral DNA Helicase Werner Inhibitor (WRNi) GSK4418959 alone or in combination with other anti-cancer agents in adult participants with Mismatch Repair-deficient (dMMR) or Microsatellite Instability-High (MSI-H) solid tumors (SYLVER)

Brief description of study

This study will test how well the oral WRN inhibitor GSK4418959 works and whether it has few side effects, both by itself and with dostarlimab, in patients with advanced cancers that have specific genetic markers called dMMR/MSI-H, including colorectal and endometrial cancer. First, patients will go through a pre-screening process to check if their tumors have these markers and see if they qualify. Those who qualify will join one of three parts of the study: Part 1 will test different doses of GSK4418959 alone in patients with advanced tumors; Part 2 will use the best dose from Part 1 to test the drug in patients with advanced colorectal or endometrial cancer; and Part 3 will test different doses of GSK4418959 combined with dostarlimab in patients with advanced tumors.


Clinical Study Identifier: s24-00812
ClinicalTrials.gov Identifier: NCT06710847
Principal Investigator: Kari E. Hacker.
Other Investigators: Elaine Shum, Erin Annette Reese, Scot Niglio, Christina Grace Wilson, Kirby Rodriguez, Janice Mehnert, Maya Dimitrova, Eneil De La Pena, Leslie R Boyd, Marina Stasenko, Jessica Wang, Joshua K Sabari, Nina Beri, David R. Wise, Douglas K Marks, Salman Rafi Punekar, Michelle Diane Swanson Lightfoot, Whitfield B. Growdon, Samantha VanMaanen, Kristen Spencer, Kathleen M Madden, Nancy Chan, Bhavana Pothuri, Kathleen M Lutz.


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