An Open-Label, First in Human, Phase 1/2 to Evaluate Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the CTPS1 Inhibitor STP938 In Adult Subjects With Relapsed/Refractory B-Cell and T-Cell Lymphomas
Summary
The Phase 1 part of the study is a dose escalation of STP938 as monotherapy. The Phase 2 part of the study is cohort expansion of STP938 as a monotherapy in 5 different B and T cell lymphomas.
Detailed description
The drug STP938 is an inhibitor of an enzyme called cytidine triphosphate synthase 1 (CTPS1). CTPS1, and a very similar enzyme cytidine triphosphate synthase 2 (CTPS2), control the final step in the production of the cytidine triphosphate (CTP). CTP is an essential building block of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Studies of people with inherited mutations of the CTPS1 gene indicate that certain types of blood cells required CTPS1 in order to divide rapidly, whereas other cells in the body use the CTPS2 enzyme. Based on these observations, it is expected that blocking CTPS1, using the drug STP938, may be an effective treatment for certain types of cancer that arise from blood cells. The purpose of this study is to see if STP938 is effective at treating different types of lymphoma. STP938 will be given as a tablet. Blood samples will be taken during the study in order to understand the effects of STP938 on the lymphoma and on the rest of the body. The main outcome of the first part of the study is to see if STP938 can be given safely to patients with lymphoma, and to work out the best dose of STP938. The main outcome of the second part of the study is to see if ST938 is effective in treating different types of lymphoma.
Arms & interventions
- DrugSTP938
Small molecule
Outcome measures
Primary
Safety and Tolerability (Phase 1 / Dose Escalation)
Incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs)
Time frame: Through study completion, an average of 9 months
Objective Response Rate (ORR) (Phase 2 / Dose Expansion)
ORR is defined as the proportion of subjects achieving a confirmed response (complete response \[CR\] or partial response \[PR\]). Evaluation of ORR will be via standard response criteria
Time frame: Through study completion, an average of 9 months
Secondary
Maximum plasma concentration (Cmax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Time frame: 16 Days
Time to reach maximum concentration (TMax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Time frame: 16 Days
Area under the curve (AUC) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Time frame: 16 Days
Evaluate preliminary clinical activity of STP938 (Phase 1)
Time frame: Through study completion, an average of 9 months
Evaluate best overall response of STP938 (Phase 1 / Phase 2)
Time frame: Through study completion, an average of 9 months
Evaluation Time To Respond (Phase 1 / Phase 2)
Time frame: Through study completion, an average of 9 months
Evaluation Duration of Response (Phase 1 / Phase 2)
Time frame: Through study completion, an average of 9 months
Evaluation Progression Free Survival (Phase 1 / Phase 2)
Time frame: Through study completion, an average of 9 months
Evaluation of Complete Response Rate (Phase 2)
Time frame: Through study completion, an average of 9 months
Safety and Tolerability (Phase 2 / Dose Expansion)
Time frame: Through study completion, an average of 9 months
Eligibility criteria
Study locations (3)
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Florida Cancer Specialists
Sarasota, Florida, 34232
Memorial Sloan Kettering
New York, New York, 10065
References
- Asnagli H, Minet N, Pfeiffer C, Hoeben E, Lane R, Laughton D, Birch L, Jones G, Novak A, Parker AE, Ludwig H, Fischer A, Latour S, Beer PA. CTP Synthase 1 Is a Novel Therapeutic Target in Lymphoma. Hemasphere. 2023 Mar 28;7(4):e864. doi: 10.1097/HS9.0000000000000864. eCollection 2023 Apr.(PubMed)