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]

NCT05179603 | Terminated Phase 2 Results DMC FDA Drug

• 5 other identifiers: ACT16941U1111-1251-5834MK-3475-C39KEYNOTE-C392021-002150-91
• Study Type: interventional
• Target: 14
• Locations: 3 countries
• Sites: 8

Brief Summary

This is a phase 2 multi-cohort, un-controlled, non-randomized, open-label, multi-center study that assessed 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 was 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 aimed 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.

Conditions

Classic Hodgkin Lymphoma; Diffuse Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  The CRR was defined as the percentage of participants who had a complete response (CR) as the best overall response (BOR) as per Investigator assessment (Lugano response criteria 2014). The BOR was defined as the BOR observed from the date of first study treatment until PD, death, cut-off date or initiation of subsequent anti-cancer therapy, whichever occurred first. CR based on computed tomography (CT)-based response: lymph nodes and extralymphatic sites with target nodes/nodal masses must regress to \<=1.5 centimeter (cm) in longest transverse diameter of a lesion (LDi) and no extralymphatic sites of disease.

  From first dose of study treatment administration (Day 1) up to approximately 21 months

Secondary Outcomes (10)

• Objective Response Rate (ORR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  From first dose of study treatment (Day 1) up to 30 days after the last dose of study treatment; approximately 29 months

• Number of Participants With Dose Limiting Toxicities (DLTs)

  From Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)

• Time to Response (TTR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months

• Duration of Response (DoR)

  From first dose of study treatment administration (Day 1) up to maximum exposure of study treatment; approximately 28 months

Study Arms (2)

Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab

EXPERIMENTAL

Participants with classic Hodgkin lymphoma (cHL) who were anti-programmed cell death-ligand 1 (PD-L1)-naïve and had received at least 2 or 3 lines of systemic therapy received pegenzileukin 24 microgram per kilogram (μg/kg) via intravenous (IV) infusion over 30 minutes on Day 1 of each cycle (each cycle is 21 days), along with pembrolizumab 200 milligram (mg) via 30 minutes IV infusion on Day 1 of each 3-week treatment cycle (each cycle is 21 days) as third-line or fourth-line (3/4L) therapy, until disease progression (PD), unacceptable adverse event (AE) or other full permanent discontinuation criteria was met or completion of Cycle 35.

Drug: THOR-707; Drug: Pembrolizumab

Cohort C1: (sub study 03) diffuse large B Cell lymphoma (DLBCL)

EXPERIMENTAL

Pegenzileukin administered every 2 weeks on Day 1 of each cycle (14 days per cycle) for up to 52 cycles.

Drug: THOR-707

Interventions

THOR-707 DRUG

Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous infusion

Also known as: Pegenzileukin

Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab; Cohort C1: (sub study 03) diffuse large B Cell lymphoma (DLBCL)

Pembrolizumab DRUG

Pharmaceutical Form: Solution for infusion Route of Administration: Intravenous infusion

Also known as: KEYTRUDA® or generic

Cohort A: Pegenzileukin 24 μg/kg + Pembrolizumab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have been ≥ 12 years of age, at the time of signing the informed consent
• Disease location was amenable to tumor biopsy at baseline
• All participants must have had a measurable disease
• Both male and female participants agreed 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.
• Had to be 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.

You may not qualify if:

• Participants were excluded from the study if any of the following criteria applied:
• 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
• Had 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 were permitted
• The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

Investigational Site Number : 0320005

CABA, Buenos Aires, 1430, Argentina

Location

Investigational Site Number : 1520003

Santiago, Reg Metropolitana de Santiago, 7500653, Chile

Location

Investigational Site Number : 1520002

Santiago, Reg Metropolitana de Santiago, 7500921, Chile

Location

Investigational Site Number : 1520004

Viña del Mar, Región de Valparaíso, 2540488, Chile

Location

Investigational Site Number : 1520001

Temuco, 4800827, Chile

Location

Investigational Site Number : 7240002

Barcelona, Barcelona [Barcelona], 08036, Spain

Location

Investigational Site Number : 7240001

L'Hospitalet de Llobregat, Barcelona [Barcelona], 08908, Spain

Location

Investigational Site Number : 7240004

Madrid / Madrid, Madrid, Comunidad de, 28040, Spain

Location

Related Links

• ACT16941 Plain Language Results Summary

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

pembrolizumab; Drugs, Generic

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Limitations and Caveats

The study was terminated based on strategic sponsor decision not driven by any safety concerns and no participants were enrolled in Cohort C1.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 5, 2022
• Study Start: December 7, 2021
• Primary Completion: September 14, 2023
• Study Completion: September 6, 2024
• Last Updated: December 24, 2025
• Results First Posted: October 2, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

AR (1); CL (4); ES (3)