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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1 (Part 1, Dose Escalation) | Experimental | Up to 5 dose levels with STP938 administered as oral monotherapy |
|
| Phase 2 (Part 2; expansion) | Experimental | At defined dose level(s) with STP938 administered as oral monotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| STP938 | Drug | Small molecule |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability (Phase 1 / Dose Escalation) | Incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs) | 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 | Through study completion, an average of 9 months |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma concentration (Cmax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation) | Pharmacokinetic parameter from plasma STP938 levels | 16 Days |
| Time to reach maximum concentration (TMax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation) |
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Main Inclusion Criteria:
Main Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Maureen Higgins | Contact | +33 1 86 26 43 56 | STP938-101@step-ph.com | |
| Duc Tran | Contact | +33 1 86 26 43 56 | STP938-101@step-ph.com |
| Name | Affiliation | Role |
|---|---|---|
| Maureen Higgins | Step Pharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Colorado Blood Cancer Institute | Recruiting | Denver | Colorado | 80218 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37008165 | Derived | 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. |
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Patients will be assigned to a dose level of STP938 (Phase 1) or an expansion cohort (Phase 2) at the time of their enrollment.
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Pharmacokinetic parameter from plasma STP938 levels |
| 16 Days |
| Area under the curve (AUC) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation) | Pharmacokinetic parameter from plasma STP938 levels | 16 Days |
| Evaluate preliminary clinical activity of STP938 (Phase 1) | Evaluation of ORR using standard response criteria | Through study completion, an average of 9 months |
| Evaluate best overall response of STP938 (Phase 1 / Phase 2) | Evaluation of best overall response (Complete response [CR], Partial response [PR], Stable disease [SD], Progression of disease [PD], Not evaluable, Not applicable) using standard response criteria | Through study completion, an average of 9 months |
| Evaluation Time To Respond (Phase 1 / Phase 2) | Time to response (TTR) defined as the time from first dose of STP938 to the date of first CR or PR response assessment | Through study completion, an average of 9 months |
| Evaluation Duration of Response (Phase 1 / Phase 2) | Duration of response (DoR) is defined as the time, in days, from the date measurement criteria that are first met for CR or PR (whichever is first recorded) to the first date that relapse, progressive disease or death, whichever occurs first | Through study completion, an average of 9 months |
| Evaluation Progression Free Survival (Phase 1 / Phase 2) | Progression-free survival (PFS) is defined as the time from first STP938 dose to the date of disease progression or death, whichever occurs first | Through study completion, an average of 9 months |
| Evaluation of Complete Response Rate (Phase 2) | Complete Response Rate using standard response criteria | Through study completion, an average of 9 months |
| Safety and Tolerability (Phase 2 / Dose Expansion) | Incidence of SAEs and TEAEs | Through study completion, an average of 9 months |
| Florida Cancer Specialists | Recruiting | Sarasota | Florida | 34232 | United States |
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| Memorial Sloan Kettering | Recruiting | New York | New York | 10065 | United States |
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| Hôpital Saint-Louis | Recruiting | Paris | Paris | 75610 | France |
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| The Centre Léon Bérard | Recruiting | Lyon | France |
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| Institut Paoli Calmettes | Recruiting | Marseille | France |
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| CHU de Nantes | Recruiting | Nantes | France |
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| Institut Gustave Roussy | Recruiting | Villejuif | France |
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| University Hospitals of Leicester NHS Trust | Recruiting | Leicester | United Kingdom |
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| Imperial College / Clinical Trials Unit, Hammersmith Hospital | Recruiting | London | United Kingdom |
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| The Christie | Recruiting | Manchester | United Kingdom |
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| Nottingham City Hospital | Recruiting | Nottingham | United Kingdom |
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| Churchill Hospital | Recruiting | Oxford | United Kingdom |
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| Derriford Hospital | Recruiting | Plymouth | United Kingdom |
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| The Royal Marsden | Recruiting | Sutton | United Kingdom |
|
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D016399 | Lymphoma, T-Cell |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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