History of Changes for Study: NCT05463263

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

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Study Record Versions

Version	Submitted Date	Changes
1	July 14, 2022	None (earliest Version on record)
2	August 3, 2022	Recruitment Status, Study Status, Contacts/Locations and Oversight
3	September 5, 2022	Study Status and Contacts/Locations
4	February 17, 2023	Contacts/Locations and Study Status
5	September 19, 2023	Contacts/Locations and Study Status

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Merged
Side-by-Side

Study Identification


Unique Protocol ID:	STP938-101
Brief Title:	A Phase 1/2 Study of STP938 for Adult Subjects With Relapsed/Refractory B-Cell and T-Cell Lymphomas
Official Title:	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
Secondary IDs:

Study Status


Record Verification:	July 2022
Overall Status:	Not yet recruiting
Study Start:	July 2022
Primary Completion:	December 2025 [Anticipated]
Study Completion:	December 2025 [Anticipated]

First Submitted:	June 30, 2022
First Submitted that Met QC Criteria:	July 14, 2022
First Posted:	July 18, 2022 [Actual]

Last Update Submitted that Met QC Criteria:	July 14, 2022
Last Update Posted:	July 18, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Step Pharma, SAS
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:

Study Description

Brief 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.

Conditions


Conditions:	Lymphoma, B-Cell Lymphoma, T-Cell
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1/Phase 2
Interventional Study Model:	Sequential Assignment
	Patients will be assigned to a dose level of STP938 (Phase 1) or an expansion cohort (Phase 2) at the time of their enrollment.
Number of Arms:	2
Masking:	None (Open Label)
Allocation:	Non-Randomized
Enrollment:	180 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
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

Outcome Measures


Primary Outcome Measures:
1.	Safety and Tolerability (Phase 1 / Dose Escalation) [ Time Frame: Through study completion, an average of 9 months ] Incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs)
2.	Objective Response Rate (ORR) (Phase 2 / Dose Expansion) [ Time Frame: Through study completion, an average of 9 months ] 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
Secondary Outcome Measures:
1.	Maximum plasma concentration (Cmax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation) [ Time Frame: 16 Days ] Pharmacokinetic parameter from plasma STP938 levels
2.	Time to reach maximum concentration (TMax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation) [ Time Frame: 16 Days ] Pharmacokinetic parameter from plasma STP938 levels
3.	Area under the curve (AUC) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation) [ Time Frame: 16 Days ] Pharmacokinetic parameter from plasma STP938 levels
4.	Evaluate preliminary clinical activity of STP938 (Phase 1) [ Time Frame: Through study completion, an average of 9 months ] Evaluation of ORR using standard response criteria
5.	Evaluate best overall response of STP938 (Phase 1 / Phase 2) [ Time Frame: Through study completion, an average of 9 months ] 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
6.	Evaluation Time To Respond (Phase 1 / Phase 2) [ Time Frame: Through study completion, an average of 9 months ] Time to response (TTR) defined as the time from first dose of STP938 to the date of first CR or PR response assessment
7.	Evaluation Duration of Response (Phase 1 / Phase 2) [ Time Frame: Through study completion, an average of 9 months ] 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
8.	Evaluation Progression Free Survival (Phase 1 / Phase 2) [ Time Frame: Through study completion, an average of 9 months ] Progression-free survival (PFS) is defined as the time from first STP938 dose to the date of disease progression or death, whichever occurs first
9.	Evaluation of Complete Response Rate (Phase 2) [ Time Frame: Through study completion, an average of 9 months ] Complete Response Rate using standard response criteria
10.	Safety and Tolerability (Phase 2 / Dose Expansion) [ Time Frame: Through study completion, an average of 9 months ] Incidence of SAEs and TEAEs

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	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.

Contacts/Locations


Central Contact Person:	Maureen Higgins, PhD Telephone: +33 1 86 26 43 56 Email: STP938-101@step-ph.com
Central Contact Backup:	Duc Tran Telephone: +33 1 86 26 43 56 Email: STP938-101@step-ph.com
Study Officials:	Ian Flinn, MD, PhD Principal Investigator Tennessee Oncology
	Manish Patel, MD Principal Investigator Florida Cancer Specialists
	Michael Tees, MD, MPH Principal Investigator Colorado Blood Cancer Institute
	Matthew Ahearne, MB ChB Principal Investigator University Hospitals, Leicester
	David Lewis, MB ChB Principal Investigator University Hospitals Plymouth NHS Trust
Locations:

IPDSharing


Plan to Share IPD:	No

References


Citations:
Links:
Available IPD/Information: