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]

Diffuse Large B-cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05179603
• Other study ID #: ACT16941
• Secondary ID: U1111-1251-5834M
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 7, 2021
• Est. completion date: January 14, 2025

Study information

• Verified date: March 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 14
• Est. completion date: January 14, 2025
• Est. primary completion date: September 14, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Classic Hodgkin Lymphoma
• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• THOR-707
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous infusion
• Pembrolizumab
Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous infusion

Locations

Country	Name	City	State
Argentina	Investigational Site Number : 0320005	Caba	Buenos Aires
Chile	Investigational Site Number : 1520002	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520003	Santiago	Reg Metropolitana De Santiago
Chile	Investigational Site Number : 1520001	Temuco
Chile	Investigational Site Number : 1520004	Vina del Mar	Valparaíso
Spain	Investigational Site Number : 7240002	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240001	Hospitalet de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240004	Madrid / Madrid	Madrid, Comunidad De

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

Argentina,  Chile,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.
Primary	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.	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	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.	21 days for Cohort A and 28 days for Cohort C1
Secondary	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.	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
Secondary	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.	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	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.	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
Secondary	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.	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
Secondary	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.	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	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.	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
Secondary	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.	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	Plasma concentration of SAR444245		Multiple timepoints up to approximately 24 months
Secondary	Incidence of anti-drug antibodies (ADAs) against SAR444245		Multiple timepoints up to approximately 24 months