A Phase 1/2 Study of STP938 for Adult Subjects With Relapsed/Refractory B-Cell and T-Cell Lymphomas

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, B-Cell; Lymphoma, T-Cell
• Intervention / Treatment: Drug: STP938

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.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Duc Tran; Phone Number: +33 1 86 26 43 56; Email: STP938-101@step-ph.com
• Study Contact Backup: Name: Maureen Higgins; Phone Number: +33 1 86 26 43 56; Email: STP938-101@step-ph.com

Study Locations

• France
  • Lyon, France
    • Recruiting
    • The Centre Léon Bérard
    • Contact: Yann Guillerman
  • Marseille, France
    • Recruiting
    • Institut Paoli Calmettes
    • Contact: Jean Laurent L'Attention; Phone Number: : +33 (0)4 9122 37 29
    • Principal Investigator: Robin Noel
  • Nantes, France
    • Recruiting
    • CHU de Nantes
    • Contact: Benoit Tessoulin
  • Villejuif, France
    • Recruiting
    • Institut Gustave Roussy
    • Contact: Vincent Ribrag
  • Paris
    • Paris, Paris, France, 75610
      • Recruiting
      • Hôpital Saint-Louis
      • Contact: Halim Bataouche
      • Principal Investigator: Adèle de Masson
• United Kingdom
  • Leicester, United Kingdom
    • Recruiting
    • University Hospitals of Leicester NHS Trust
    • Contact: Matthew Ahearne
  • London, United Kingdom
    • Recruiting
    • Imperial College / Clinical Trials Unit, Hammersmith Hospital
    • Contact: Lucy Cook; Phone Number: 0203 313 4340
  • Manchester, United Kingdom
    • Recruiting
    • The Christie
    • Contact: Kim Linton
  • Nottingham, United Kingdom
    • Recruiting
    • Nottingham City Hospital
    • Contact: Chris Fox
  • Oxford, United Kingdom
    • Recruiting
    • Churchill Hospital
    • Contact: Graham Collins
  • Plymouth, United Kingdom
    • Recruiting
    • Derriford Hospital
    • Contact: David Lewis
  • Sutton, United Kingdom
    • Recruiting
    • The Royal Marsden
    • Contact: Dima El Sharkawi; Email: HaemOncGT@rmh.nhs.uk
• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Colorado Blood Cancer Institute
      • Contact: M Tees
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists
      • Contact: M Patel
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering
      • Contact: Robert Stuver; Phone Number: 646-608-4308
      • Principal Investigator: Robert Stuver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

• Signed and dated informed consent, and able to comply with the study procedures and any locally required authorization.
• Male or female aged ≥ 18 years.
• Relapsed/refractory patients with histologically confirmed diagnosis of B cell or T cell lymphoma
• Must have received at least 2 prior systemic therapies and have no treatment options known to provide clinical benefit
• Must have measurable disease per Lugano lymphoma classification except for cutaneous T-cell lymphoma (CTCL) which is measured via International Society for Cutaneous Lymphomas (ISCL)/ European Organization of Research and Treatment of Cancer (EORTC).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Life expectancy > 3 months as assessed by the Investigator.
• Adequate organ function (bone marrow, hepatic, renal function and coagulation).
• All toxicities (except alopecia) from prior cancer treatments or procedures must have resolved to ≤Grade 1 or returned to baseline levels prior to enrollment.

Main Exclusion Criteria:

• Pregnant or breastfeeding females and women of child bearing potential or males unwilling to comply with contraception requirements.
• Known carcinomatous meningitis or central nervous system (CNS) involvement with lymphoma.
• Active malignancy within 2 years of study enrollment
• Prior radiation or surgical resection of their lymphoma without additional sites of measurable disease outside of the radiation field or subjects who have received prior radiation or surgical resection of their lymphoma ≤2 weeks prior to the first dose of study drug.
• Systemic cancer treatments, monoclonal antibody-directed therapies, other investigational agents within 4 weeks before enrollment, or <5 half-lives since completion of previous investigational therapy, whichever is shorter.
• Uncontrolled intercurrent illness.
• Immunocompromised subjects with increased risk of opportunistic infections or history of opportunistic infection in the last 12 months.
• Known active or chronic hepatitis B or active hepatitis C virus (HCV) infection.
• Subjects who have received a live vaccine within 30 days prior to study enrollment or whilst participating in the study.
• Subjects with corrected QT interval >470 msec based on averaged triplicate electrocardiogram (ECG) readings at the Screening Visit using the QT interval corrected for heart rate using Fridericia's method (QTcF).
• Subjects who received a severe acute respiratory syndrome coronavirus 2 vaccine ≤3 weeks prior to study drug dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 (Part 1, Dose Escalation); Up to 5 dose levels with STP938 administered as oral monotherapy	Drug: STP938; Small molecule
Experimental: Phase 2 (Part 2; expansion); At defined dose level(s) with STP938 administered as oral monotherapy	Drug: STP938; Small molecule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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)	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

Collaborators and Investigators

• Sponsor: Step Pharma, SAS
• Investigators: Study Director: Maureen Higgins, Step Pharma

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell; Lymphoma, T-Cell
• Other Study ID Numbers: STP938-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No