An Open-Label, Phase 1 Study to Evaluate Safety, Tolerability and Pharmacokinetics of the CTPS1 Inhibitor STP938 in Adult Subjects withAdvanced Solid Tumors, with a Safety Expansion in Advanced CTPS2 Null Ovarian Cancer
Recipient organisationNIHR University College London Hospitals Biomedical Research Centre
NIHR supportRecorded as supported by this research centre
PeriodJan 2025 — Jun 2028
In plain English
AI plain-English summary
A new drug, STP938, is being tested in up to 70 patients with advanced solid tumours who have exhausted all standard treatment options. This matters because many cancers, particularly ovarian cancer, become resistant to existing therapies. STP938 works by blocking an enzyme called CTPS1, which cancer cells rely on to make DNA building blocks. Healthy cells can use a backup enzyme (CTPS2), but some ovarian cancers lack this backup, making them selectively vulnerable to the drug. The trial first finds a safe dose in patients with various solid tumours, then tests that dose specifically in 10 patients with CTPS2-deficient ovarian cancer. If successful, this could offer a new treatment option for patients with no remaining standard therapies. For ovarian cancer patients whose tumours lack CTPS2, it might provide a targeted therapy where none currently exists. The approach could also be expanded to other cancer types that share this genetic vulnerability. The study is a first-in-human trial, so its primary goal is safety and dosing—not yet proving the drug works.
View original technical description
STP938 is a novel, potent orally available inhibitor of cytidine triphosphate synthase 1 (CTPS1). STP938-201 is an open-label, phase 1a/1b study which will explore STP938 in adult subjects with advanced solid tumors who have failed all available therapies known to be associated with clinical benefit, or are not eligible for, or refused standard of care (SOC). The study will be conducted in 2 parts. Part 1 (the phase 1a portion of the study) will consist of single agent STP938 dose escalation and exploration of different dosing schedules in order to establish the recommended Phase 2 dose (RP2D). The RP2D will be the lowest safe and biologically effective dose (and schedule) based on safety, efficacy, pharmacokinetic and pharmacodynamic data. Part 2 (the phase 1b portion of the study) will consist of a safety expansion cohort (10 subjects) at the RP2D for adult subjects with advanced ovarian cancer lacking CTPS2 expression; subjects will have failed, refused or be ineligible for SOC therapy. A second safety expansion cohort may be opened to recruit subjects in a second cancer type with a high prevalence of CTPS2 loss. The study will involve up to 70 patients at approximately 20 cancer centres in the United States, Europe and the United Kingdom.The anticipated median approximate duration of the study treatment is 3-6 months (13-14 visits). After the end of trial visit, subjects who have not progressed, relapsed or started subsequent anticancer treatment will be followed for up to 12 months, by telephone, every 3 months. Participants will receive STP938 capsules twice daily in 28 (or 21) day treatment cycles if they are tolerating the treatment, and it is deemed beneficial. The response to the treatment will be assessed by radiographic tumour assessment, using either a CT Scan or MRI . The following study procedures will be performed: (a) physical examinations(b) ECGs (c) blood tests, (d) urine tests (e) CT/MRI scans (f) tumour biopsies.
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