Clinical trial NCT05463263: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Lymphoma, B-Cell
Lymphoma, T-Cell
Lead sponsor: Step Pharma, SAS
Sponsor class: INDUSTRY
First posted: 2022-07-18
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Patients will be assigned to a dose level of STP938 (Phase 1) or an expansion cohort (Phase 2) at the time of their enrollment.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Safety and Tolerability (Phase 1 / Dose Escalation)
timeFrame: Through study completion, an average of 9 months
measure: Objective Response Rate (ORR) (Phase 2 / Dose Expansion)
timeFrame: Through study completion, an average of 9 months
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
timeFrame: 16 Days
measure: Time to reach maximum concentration (TMax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
timeFrame: 16 Days
measure: Area under the curve (AUC) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
timeFrame: 16 Days
measure: Evaluate preliminary clinical activity of STP938 (Phase 1)
timeFrame: Through study completion, an average of 9 months
measure: Evaluate best overall response of STP938 (Phase 1 / Phase 2)
timeFrame: Through study completion, an average of 9 months
measure: Evaluation Time To Respond (Phase 1 / Phase 2)
timeFrame: Through study completion, an average of 9 months
measure: Evaluation Duration of Response (Phase 1 / Phase 2)
timeFrame: Through study completion, an average of 9 months
measure: Evaluation Progression Free Survival (Phase 1 / Phase 2)
timeFrame: Through study completion, an average of 9 months
measure: Evaluation of Complete Response Rate (Phase 2)
timeFrame: Through study completion, an average of 9 months
measure: Safety and Tolerability (Phase 2 / Dose Expansion)
timeFrame: Through study completion, an average of 9 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: New York
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Lyon
country: France
facility: The Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
city: London
country: United Kingdom
facility: Imperial College / Clinical Trials Unit, Hammersmith Hospital
city: Manchester
country: United Kingdom
facility: The Christie
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden
Study officials:
affiliation: Step Pharma
name: Maureen Higgins
role: STUDY_DIRECTOR
References: