Back to resultsA Phase 1/2 Study of STP938 for Adult Subjects With Relapsed/Refractory B-Cell and T-Cell Lymphomas
Primary Purpose
Lymphoma, B-Cell, Lymphoma, T-Cell
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
STP938
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, B-Cell
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.
Sites / Locations
- Colorado Blood Cancer InstituteRecruiting
- Florida Cancer SpecialistsRecruiting
- The Centre Léon BérardRecruiting
- Institut Paoli CalmettesRecruiting
- CHU de NantesRecruiting
- Institut Gustave RoussyRecruiting
- University Hospitals of Leicester NHS TrustRecruiting
- Imperial College / Clinical Trials Unit, Hammersmith HospitalRecruiting
- The ChristieRecruiting
- Nottingham City HospitalRecruiting
- Churchill HospitalRecruiting
- Derriford HospitalRecruiting
- The Royal MarsdenRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Phase 1 (Part 1, Dose Escalation)
Phase 2 (Part 2; expansion)
Arm Description
Up to 5 dose levels with STP938 administered as oral monotherapy
At defined dose level(s) with STP938 administered as oral monotherapy
Outcomes
Primary Outcome Measures
Safety and Tolerability (Phase 1 / Dose Escalation)
Incidence of dose limiting toxicities (DLTs), serious adverse events (SAEs), treatment-emergent adverse events (TEAEs)
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
Secondary Outcome Measures
Maximum plasma concentration (Cmax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Pharmacokinetic parameter from plasma STP938 levels
Time to reach maximum concentration (TMax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Pharmacokinetic parameter from plasma STP938 levels
Area under the curve (AUC) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Pharmacokinetic parameter from plasma STP938 levels
Evaluate preliminary clinical activity of STP938 (Phase 1)
Evaluation of ORR using standard response criteria
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
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
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
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
Evaluation of Complete Response Rate (Phase 2)
Complete Response Rate using standard response criteria
Safety and Tolerability (Phase 2 / Dose Expansion)
Incidence of SAEs and TEAEs
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05463263
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 3, 2022 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Step Pharma, SAS
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, B-Cell, Lymphoma, T-Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
180 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 (Part 1, Dose Escalation)
Arm Type
Experimental
Arm Description
Up to 5 dose levels with STP938 administered as oral monotherapy
Arm Title
Phase 2 (Part 2; expansion)
Arm Type
Experimental
Arm Description
At defined dose level(s) with STP938 administered as oral monotherapy
Intervention Type
Drug
Intervention Name(s)
STP938
Intervention Description
Small molecule
Primary Outcome Measure Information:
Title
Safety and Tolerability (Phase 1 / Dose Escalation)
Description
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
Title
Objective Response Rate (ORR) (Phase 2 / Dose Expansion)
Description
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 Outcome Measure Information:
Title
Maximum plasma concentration (Cmax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Description
Pharmacokinetic parameter from plasma STP938 levels
Time Frame
16 Days
Title
Time to reach maximum concentration (TMax) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Description
Pharmacokinetic parameter from plasma STP938 levels
Time Frame
16 Days
Title
Area under the curve (AUC) of STP938 including effects of food on absorption (Phase 1 / Dose Escalation)
Description
Pharmacokinetic parameter from plasma STP938 levels
Time Frame
16 Days
Title
Evaluate preliminary clinical activity of STP938 (Phase 1)
Description
Evaluation of ORR using standard response criteria
Time Frame
Through study completion, an average of 9 months
Title
Evaluate best overall response of STP938 (Phase 1 / Phase 2)
Description
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
Time Frame
Through study completion, an average of 9 months
Title
Evaluation Time To Respond (Phase 1 / Phase 2)
Description
Time to response (TTR) defined as the time from first dose of STP938 to the date of first CR or PR response assessment
Time Frame
Through study completion, an average of 9 months
Title
Evaluation Duration of Response (Phase 1 / Phase 2)
Description
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
Time Frame
Through study completion, an average of 9 months
Title
Evaluation Progression Free Survival (Phase 1 / Phase 2)
Description
Progression-free survival (PFS) is defined as the time from first STP938 dose to the date of disease progression or death, whichever occurs first
Time Frame
Through study completion, an average of 9 months
Title
Evaluation of Complete Response Rate (Phase 2)
Description
Complete Response Rate using standard response criteria
Time Frame
Through study completion, an average of 9 months
Title
Safety and Tolerability (Phase 2 / Dose Expansion)
Description
Incidence of SAEs and TEAEs
Time Frame
Through study completion, an average of 9 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maureen Higgins
Phone
+33 1 86 26 43 56
Email
STP938-101@step-ph.com
First Name & Middle Initial & Last Name or Official Title & Degree
Duc Tran
Phone
+33 1 86 26 43 56
Email
STP938-101@step-ph.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maureen Higgins
Organizational Affiliation
Step Pharma
Official's Role
Study Director
Facility Information:
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M Tees
Facility Name
Florida Cancer Specialists
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M Patel
Facility Name
The Centre Léon Bérard
City
Lyon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yann Guillerman
Facility Name
Institut Paoli Calmettes
City
Marseille
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robin Noel
First Name & Middle Initial & Last Name & Degree
Jean Laurent L'Attention
Phone
: +33 (0)4 9122 37 29
Facility Name
CHU de Nantes
City
Nantes
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benoit Tessoulin
Facility Name
Institut Gustave Roussy
City
Villejuif
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent Ribrag
Facility Name
University Hospitals of Leicester NHS Trust
City
Leicester
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Ahearne
Facility Name
Imperial College / Clinical Trials Unit, Hammersmith Hospital
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucy Cook
Phone
0203 313 4340
Facility Name
The Christie
City
Manchester
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kim Linton
Facility Name
Nottingham City Hospital
City
Nottingham
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chris Fox
Facility Name
Churchill Hospital
City
Oxford
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Graham Collins
Facility Name
Derriford Hospital
City
Plymouth
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Lewis
Facility Name
The Royal Marsden
City
Sutton
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dima El Sharkawi
Email
HaemOncGT@rmh.nhs.uk
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase 1/2 Study of STP938 for Adult Subjects With Relapsed/Refractory B-Cell and T-Cell Lymphomas
We'll reach out to this number within 24 hrs