Back to resultsA Study of SAR444245 With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma (Master Protocol) [Pegathor Lymphoma 205]
Primary Purpose
Classic Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
THOR-707
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Classic Hodgkin Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Participants must be ≥ 12 years of age, at the time of signing the informed consent
- Disease location amenable to tumor biopsy at baseline
- All participants must have a measurable disease
- Both male and female participants agree to use approved contraception methods; not pregnant or breastfeeding for female participants; no donation or cryopreservation of eggs (ova, oocytes) for female participants and sperms for male participants.
- Capable of giving signed informed consent
For cohort A: Histologically or cytologically confirmed diagnosis of classic Hodgkin lymphoma (cHL), must have received at least two prior lines of systemic therapy for cHL, including at least one containing an anthracycline or brentuximab.
For cohort C1: Histologically confirmed diagnosis of diffuse large B Cell lymphoma (DLBCL), must have received at least two prior lines of systemic therapy for DLBCL, including one containing a combination of anthracycline and rituximab (or another anti-CD20 agent), with the last line of therapy a Health Authority approved CD19-directed CAR-T therapy. Patients must have BOR (Best Overall Response) of stable disease (SD) or progressive disease (PD) after CD-19 directed CAR-T therapy.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
- Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 (≥ 16 years old). Lansky Scale (< 16 years old) ≤ 60%
- Poor bone marrow reserve
- Poor organ function
- Participants with baseline oxygen saturation (SpO2) ≤ 92% (without oxygen therapy)
- Lymphomatous involvement of the central nervous system
- History of allogenic or solid organ transplant
- Prior IV or subcutaneous anticancer therapy, investigational agent, major surgery within 21 days prior to initiation of IMP; oral anticancer therapy within 5 half-lives or completed palliative radiotherapy within 21 days prior to initiation of IMP
- Has received prior IL-2-based anticancer treatment
- Comorbidity requiring corticosteroid therapy
- Antibiotic use (excluding topical antibiotics) ≤ 14 days prior to first dose of IMP
- Severe or unstable cardiac condition within 6 months prior to starting study treatment
- Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years-Known second malignancy either progressing or requiring active treatment within the last 3 years
- Receipt of a live or live attenuated virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines or SARS-CoV-2 vaccine that do not contain live virus are permitted
The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number :0320005
- Investigational Site Number :0320002
- Investigational Site Number :1520003
- Investigational Site Number :1520002
- Investigational Site Number :1520004
- Investigational Site Number :1520001
- Investigational Site Number :3760002
- Investigational Site Number :3800002
- Investigational Site Number :4840001
- Investigational Site Number :7240005
- Investigational Site Number :7240002
- Investigational Site Number :7240001
- Investigational Site Number :7240003
- Investigational Site Number :7240004
- Investigational Site Number :7240006
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A: (sub study 01) classic Hodgkin lymphoma (cHL)
Cohort C1: (sub study 03) diffuse large B Cell lymphoma (DLBCL)
Arm Description
SAR444245 and pembrolizumab administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
SAR444245 administered every 2 weeks on Day 1 of each cycle (14 days per cycle) for up to 52 cycles.
Outcomes
Primary Outcome Measures
Complete Response Rate- Cohort A
Cohorts A:
Complete response rate (CRR) defined as the proportion of participants who have a complete response (CR) determined by Investigator per Lugano response criteria 2014.
Objective Response Rate- Cohort C1
Cohort C1:
Objective response rate (ORR) defined as the proportion of participants who have CR or partial response (PR) determined by Investigator per Lugano response criteria 2014.
Secondary Outcome Measures
Incidence of Dose-limiting toxicities (DLTs)
DLTs assessed during DLT observation period to confirm the dose of SAR444245 when combined with or without other anticancer therapies.
Incidence of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities
Safety profile of SAR444245 when combined with or without other anticancer therapies assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings.
Objective Response Rate- Cohort A
Cohort A:
Objective response rate (ORR) defined as the proportion of participants who have CR or partial response (PR) determined by Investigator per Lugano response criteria 2014.
Time to Response (TTR)
TTR defined as the time from the first administration of IMP to the first documented evidence of PR or CR determined by Investigator per Lugano response criteria 2014.
Duration of Response (DoR)
DoR defined as the time from first documented evidence of PR or CR until progressive disease (PD) determined by Investigator per Lugano response criteria 2014, or death from any cause, whichever occurs first.
Clinical Benefit Rate (CBR)
CBR defined as CR or PR at any time or stable disease (SD) of at least 6 months determined by Investigator per Lugano response criteria 2014.
Progression free survival (PFS)
PFS defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by Investigator per Lugano response criteria 2014 or death due to any cause, whichever occurs first.
Complete response rate- Cohort C1
Cohort C1:
Complete response rate (CRR) defined as the proportion of participants who have a CR determined by Investigator per Lugano response criteria 2014.
Plasma concentration of SAR444245
Incidence of anti-drug antibodies (ADAs) against SAR444245
Full Information
NCT ID
NCT05179603
First Posted
December 16, 2021
Last Updated
September 22, 2023
Sponsor
Sanofi
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT05179603
Brief Title
A Study of SAR444245 With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma (Master Protocol) [Pegathor Lymphoma 205]
Official Title
Phase 2 Non-randomized, Open-label, Multi-cohort, Multicenter Study Assessing the Clinical Benefit of SAR444245 (THOR-707) With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 7, 2021 (Actual)
Primary Completion Date
September 14, 2023 (Actual)
Study Completion Date
September 15, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The is a phase 2 multi-cohort, un-controlled, non-randomized, open-label, multi-center study assessing the antitumor activity and safety of non-alpha interleukin (IL-2) SAR444245 with or without other anticancer therapies in participants aged 12 years and older with relapsed or refractory B cell lymphoma. This study is structured as a master protocol with separate sub studies designed to investigate the use of SAR444245 either with or without other anticancer therapies for the treatment of relapsed or refractory B cell lymphoma.
Substudy 1-Cohort A aims to establish safety and preliminary anti-tumor activity for non-alpha interleukin (IL-2) SAR444245 combined with the anti-PD1 antibody, pembrolizumab in trial participants with classic Hodgkin lymphoma (cHL) who are anti-PD-(L)1-naive and have received at least 2 or 3 lines of systemic therapy.
Substudy 3-Cohort C1 aims to establish safety and preliminary anti-tumor activity for SAR444245 as monotherapy in trial participants with diffuse large B-cell lymphoma (DLBCL). Trial participants in this study must have received at least 2 lines of systemic therapy and have either stable or progressive disease 1-3 months post Health Authority approved Chimeric Antigen Receptor T-cell (CAR-T) treatment when given as last systemic treatment prior to study enrollment.
Detailed Description
The duration of the study for an individual patient will start from the signature of the main informed consent and include:
a screening period of up to 28 days;
a treatment period [max] 35 cycles (21 days per cycle) for Cohort A and 52 cycles (14 days per cycle) for Cohort C1 or until occurrence of unacceptable toxicities or until PD;
an end-of-treatment visit at least approximately 30 days following the last administration of study drug (or until the patient receives another anticancer therapy, whichever is earlier);
and a follow-up visits 3 months after treatment discontinuation and every 3 months thereafter following, until disease progression, or initiation of another antitumor treatment, or death, whichever is earlier.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Classic Hodgkin Lymphoma, Diffuse Large B-cell Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort A: (sub study 01) classic Hodgkin lymphoma (cHL)
Arm Type
Experimental
Arm Description
SAR444245 and pembrolizumab administered every 3 weeks on Day 1 of each cycle (21 days per cycle) for up to 35 cycles.
Arm Title
Cohort C1: (sub study 03) diffuse large B Cell lymphoma (DLBCL)
Arm Type
Experimental
Arm Description
SAR444245 administered every 2 weeks on Day 1 of each cycle (14 days per cycle) for up to 52 cycles.
Intervention Type
Drug
Intervention Name(s)
THOR-707
Intervention Description
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda® or generic
Intervention Description
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous infusion
Primary Outcome Measure Information:
Title
Complete Response Rate- Cohort A
Description
Cohorts A:
Complete response rate (CRR) defined as the proportion of participants who have a complete response (CR) determined by Investigator per Lugano response criteria 2014.
Time Frame
Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
Title
Objective Response Rate- Cohort C1
Description
Cohort C1:
Objective response rate (ORR) defined as the proportion of participants who have CR or partial response (PR) determined by Investigator per Lugano response criteria 2014.
Time Frame
Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
Secondary Outcome Measure Information:
Title
Incidence of Dose-limiting toxicities (DLTs)
Description
DLTs assessed during DLT observation period to confirm the dose of SAR444245 when combined with or without other anticancer therapies.
Time Frame
21 days for Cohort A and 28 days for Cohort C1
Title
Incidence of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities
Description
Safety profile of SAR444245 when combined with or without other anticancer therapies assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) V5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) consensus gradings.
Time Frame
From first investigational medicinal product (IMP) dose up to 30 days for TEAEs or up to 90 days for SAE after the last dose of IMP i.e., up to approximately 27 months
Title
Objective Response Rate- Cohort A
Description
Cohort A:
Objective response rate (ORR) defined as the proportion of participants who have CR or partial response (PR) determined by Investigator per Lugano response criteria 2014.
Time Frame
Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
Title
Time to Response (TTR)
Description
TTR defined as the time from the first administration of IMP to the first documented evidence of PR or CR determined by Investigator per Lugano response criteria 2014.
Time Frame
From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 36 months
Title
Duration of Response (DoR)
Description
DoR defined as the time from first documented evidence of PR or CR until progressive disease (PD) determined by Investigator per Lugano response criteria 2014, or death from any cause, whichever occurs first.
Time Frame
From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 36 months
Title
Clinical Benefit Rate (CBR)
Description
CBR defined as CR or PR at any time or stable disease (SD) of at least 6 months determined by Investigator per Lugano response criteria 2014.
Time Frame
Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
Title
Progression free survival (PFS)
Description
PFS defined as the time from the date of first IMP administration to the date of the first documented disease progression determined by Investigator per Lugano response criteria 2014 or death due to any cause, whichever occurs first.
Time Frame
From the date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to approximately 36 months
Title
Complete response rate- Cohort C1
Description
Cohort C1:
Complete response rate (CRR) defined as the proportion of participants who have a CR determined by Investigator per Lugano response criteria 2014.
Time Frame
Baseline to the date of first documented progression or initiation of subsequent anticancer therapy or approximately 8 months after the last participant receive first dose.
Title
Plasma concentration of SAR444245
Time Frame
Multiple timepoints up to approximately 24 months
Title
Incidence of anti-drug antibodies (ADAs) against SAR444245
Time Frame
Multiple timepoints up to approximately 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants must be ≥ 12 years of age, at the time of signing the informed consent
Disease location amenable to tumor biopsy at baseline
All participants must have a measurable disease
Both male and female participants agree to use approved contraception methods; not pregnant or breastfeeding for female participants; no donation or cryopreservation of eggs (ova, oocytes) for female participants and sperms for male participants.
Capable of giving signed informed consent
For cohort A: Histologically or cytologically confirmed diagnosis of classic Hodgkin lymphoma (cHL), must have received at least two prior lines of systemic therapy for cHL, including at least one containing an anthracycline or brentuximab.
For cohort C1: Histologically confirmed diagnosis of diffuse large B Cell lymphoma (DLBCL), must have received at least two prior lines of systemic therapy for DLBCL, including one containing a combination of anthracycline and rituximab (or another anti-CD20 agent), with the last line of therapy a Health Authority approved CD19-directed CAR-T therapy. Patients must have BOR (Best Overall Response) of stable disease (SD) or progressive disease (PD) after CD-19 directed CAR-T therapy.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 (≥ 16 years old). Lansky Scale (< 16 years old) ≤ 60%
Poor bone marrow reserve
Poor organ function
Participants with baseline oxygen saturation (SpO2) ≤ 92% (without oxygen therapy)
Lymphomatous involvement of the central nervous system
History of allogenic or solid organ transplant
Prior IV or subcutaneous anticancer therapy, investigational agent, major surgery within 21 days prior to initiation of IMP; oral anticancer therapy within 5 half-lives or completed palliative radiotherapy within 21 days prior to initiation of IMP
Has received prior IL-2-based anticancer treatment
Comorbidity requiring corticosteroid therapy
Antibiotic use (excluding topical antibiotics) ≤ 14 days prior to first dose of IMP
Severe or unstable cardiac condition within 6 months prior to starting study treatment
Active, known, or suspected autoimmune disease that has required systemic treatment in the past 2 years-Known second malignancy either progressing or requiring active treatment within the last 3 years
Receipt of a live or live attenuated virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines or SARS-CoV-2 vaccine that do not contain live virus are permitted
The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :0320005
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
1430
Country
Argentina
Facility Name
Investigational Site Number :0320002
City
Buenos Aires
ZIP/Postal Code
1426ANZ
Country
Argentina
Facility Name
Investigational Site Number :1520003
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
7500653
Country
Chile
Facility Name
Investigational Site Number :1520002
City
Santiago
State/Province
Reg Metropolitana De Santiago
ZIP/Postal Code
7500921
Country
Chile
Facility Name
Investigational Site Number :1520004
City
Vina del Mar
State/Province
Valparaíso
ZIP/Postal Code
2540488
Country
Chile
Facility Name
Investigational Site Number :1520001
City
Temuco
ZIP/Postal Code
4800827
Country
Chile
Facility Name
Investigational Site Number :3760002
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Investigational Site Number :3800002
City
Meldola (FC)
State/Province
Emilia-Romagna
ZIP/Postal Code
47014
Country
Italy
Facility Name
Investigational Site Number :4840001
City
Monterrey
State/Province
Nuevo León
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Investigational Site Number :7240005
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08035
Country
Spain
Facility Name
Investigational Site Number :7240002
City
Barcelona
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08036
Country
Spain
Facility Name
Investigational Site Number :7240001
City
Hospitalet de Llobregat
State/Province
Barcelona [Barcelona]
ZIP/Postal Code
08908
Country
Spain
Facility Name
Investigational Site Number :7240003
City
Esplugues de Llobregat
State/Province
Catalunya [Cataluña]
ZIP/Postal Code
08950
Country
Spain
Facility Name
Investigational Site Number :7240004
City
Madrid / Madrid
State/Province
Madrid, Comunidad De
ZIP/Postal Code
28040
Country
Spain
Facility Name
Investigational Site Number :7240006
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Learn more about this trial
A Study of SAR444245 With or Without Other Anticancer Therapies for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Lymphoma (Master Protocol) [Pegathor Lymphoma 205]
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