A Study to Evaluate the Safety and Activity of SAR448501/DR-0201 in Patients With Relapsed/ Refractory B-Cell Non-Hodgkin Lymphoma

A Multicenter, Multiple Expansion Cohort Phase 1 Study Evaluating the Safety and Activity of SAR448501/DR-0201 as Multiple Ascending Doses in Patients With Relapsed/Refractory B Cell Non-Hodgkin Lymphoma

This is an open-label, multiple ascending dose (MAD), phase 1 study in adult patients with relapsed or refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL). The purpose of the study is to identify possible optimal biological dosage(s) by assessing safety, tolerability, pharmacokinetics (PK), pharmacodynamics, clinical activity and immunogenicity of SAR448501/DR-0201.

The study duration per participant will be approximately 3 years, including a screening period of up to 28 days, a treatment period of 52 weeks, a safety follow-up period of approximately 28 days and a long-term follow-up period of every 3 months until withdrawal of consent, participant death or study closure, whichever is sooner.

Study Overview

• Status: Recruiting
• Conditions: B-cell Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: SAR448501

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free for US & Canada); Phone Number: option 6 800-633-1610; Email: Contact-US@sanofi.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Investigational Site Number : 001-203
  • Queensland
    • Townsville, Queensland, Australia, 4814
      • Recruiting
      • Investigational Site Number : 001-202
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Investigational Site Number : 001-205
  • Victoria
    • Melbourne, Victoria, Australia, 3121
      • Recruiting
      • Investigational Site Number : 001-204
  • Western Australia
    • Perth, Western Australia, Australia, 6009
      • Recruiting
      • Investigational Site Number : 001-201
• Serbia
  • Kamenitz, Serbia, 21204
    • Active, not recruiting
    • Investigational Site Number : 001-703
• Singapore
  • Singapore, Singapore, 119074
    • Recruiting
    • Investigational Site Number : 001-601
  • Singapore, Singapore, 308433
    • Recruiting
    • Investigational Site Number : 001-602
• South Korea
  • Busan, South Korea, 48108
    • Recruiting
    • Investigational Site Number : 001-401
  • Busan, South Korea, 49201
    • Recruiting
    • Investigational Site Number : 001-403
  • Goyang-si, South Korea, 10408
    • Recruiting
    • Investigational Site Number : 001-404
  • Seoul, South Korea, 03080
    • Recruiting
    • Investigational Site Number : 001-402
  • Seoul, South Korea, 06351
    • Recruiting
    • Investigational Site Number : 001-405
• Taiwan
  • Changhua, Taiwan, 505
    • Recruiting
    • Investigational Site Number : 001-503
  • Kaohsiung City, Taiwan, 83301
    • Recruiting
    • Investigational Site Number : 001-502
  • Taipei, Taiwan, 10048
    • Recruiting
    • Investigational Site Number : 001-501

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with R/R B-NHL which has failed at least 2 prior lines available life-prolonging standard therapy and without treatment options that are recognized to offer clinical benefit.
• Adequate marrow reserve, renal function, and hepatic function.
• Measurable disease defined as ≥ 1 bi-dimensionally measurable nodal lesion of > 1.5 cm in the longest dimension for participants with fluorodeoxyglucose (FDG)-avid disease for subtypes with nodular disease or at least one bi-dimensionally measurable extranodal lesion, defined as > 1.0 cm in its longest dimension.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Life expectancy of ≥ 12 weeks.
• Use of a highly effective contraceptive measure for all males and all females of childbearing potential during study through 180 days post last dose; Females of childbearing potential need to have a negative serum pregnancy test within 7 days prior to first dose.
• Tumor tissue block or 3 to 5 unstained slides from lymph node or other relevant biopsy collected in the past 12 months. Participants must be willing to provide a baseline and at least 1 on-treatment biopsy, unless not safely accessible.
• Participants who have received prior CAR-T therapy must be >60 days post CAR-T at day of first dosing.

Exclusion Criteria:

• Burkitt's or Burkitt's like lymphoma or lymphoplastic lymphoma.
• Current history of central nervous system (CNS) involvement by malignancy.
• Prior allogeneic stem cell transplantation except for those with follicular lymphoma (FL) and mantle cell lymphoma (MCL), who are excluded if transplant occurred less than 100 days prior to dosing or if they exhibit grade > 1 graft versus host disease.
• Prior solid organ transplantation.
• Autologous stem cell transplantation ≤ 100 days prior to dosing.
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematous, rheumatoid arthritis, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjorgen's syndrome, Guillain-Barre-syndrome, multiple sclerosis vasculitis, or glomerulonephritis (participants with a remote history of, or well-controlled autoimmune disease, may be eligible).
• Major surgery in the last 28 days prior to dosing.
• Evidence of significant, uncontrolled concomitant disease that could affect compliance with study.
• Current or past history of CNS disease (participants with remote history of non-lymphoma CNS disease and with no residual neurologic deficits may be eligible to enroll).
• QT interval corrected by Fridericia's formula (QTcF) > 480 msec.
• Significant cardiovascular disease.
• Received any anticancer systemic therapy within 4 weeks prior to first drug administration or 5 half-lives of the drug, whatever is shorter. Treatment with corticosteroid ≤ 25 mg/day prednisone or equivalent is allowed. Inhaled and topical steroids are allowed.
• Known infection with HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Active infection at baseline requiring systemic treatment with antimicrobial, antifungal, or antiviral agents in the 2 weeks prior to dosing.
• Administration of a live, attenuated vaccine within 4 weeks prior to first drug administration or anticipation that such vaccine administration would be necessary during the course of the study.
• Another invasive malignancy in the last 2 years (except basal cell carcinoma or squamous cell carcinoma of the skin, asymptomatic prostate cancer requiring only hormonal therapy and with normal prostate-specific antigen for > 1 year, and tumors deemed by the investigator to be of low likelihood for recurrence).
• Prothrombin time/international normalized ratio (INR) and activated partial thromboplastin time or partial thromboplastin time (aPTT/PTT) > 1.3 × ULN or outside the therapeutic range of the local laboratory if receiving therapeutic anticoagulation that would affect the prothrombin time/INR, participants with a history of a hypercoagulation event within 6 months, or participants who have known hypercoagulation risk factors will be excluded.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAR448501 dose escalation; SAR448501 will be administered for up to 52 weeks. Different cohorts with up to 8 dose levels will be included.	Drug: SAR448501; Bispecific antibody; Other Names: DR-0201

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse event (TEAE)		Baseline to 28 days post last dose
Potential pharmacologically optimized dose/regimen(s) of SAR448501 / DR-0201 in participants with R/R B-NHL	Potential pharmacologically optimized dose/regimen(s) of SAR448501/DR-0201 in participants with R/R B-NHL as determined using an integrated assessment of efficacy, safety, pharmacokinetic (PK)/pharmacodynamic (PD), and exposure-response relationships	Cycle 1 (Day 1 to Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate assessed for CLL	Response rate assessed for chronic lymphocytic leukemia (CLL) by International Workshop on Chronic Lymphocytic Leukemia (iwCLL). The iwCLL response is based on the overall physical examination and evaluation of blood and bone marrow: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD).	Baseline until disease progression (up to the end of treatment at Week 52)
Response rate assessed for all other B-NHL lymphomas	Response rate assessed for all other B-NHL lymphomas by Lugano response criteria. The Lugano response is based on the overall radiographic response: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), not evaluable (NE) and not available (NA).	Baseline until disease progression (up to the end of treatment at Week 52)
Duration of response/remission (DOR)	DOR is defined as the time between first disease response and date of disease progression or death due to any cause, whichever occurs first.	Baseline until disease progression (up to the end of treatment at Week 52)
Complete response/remission rate (CRR)	Proportion of participants who have a complete response/remission, based on the disease assessments by the Investigator.	Baseline until the end of treatment (Week 52)
Time to response (TTR in months)	TRR is defined as the time between the first administration of investigational medicinal product (IMP) at Cycle 1 Day 1 (C1D1) until first documented disease response.	Baseline until the end of treatment (Week 52)
Progression-free survival (PFS)	PFS is defined as the time between the first administration of IMP at C1D1 and date of disease progression or death due to any case, whichever occurs first.	Baseline until disease progression (up to the end of treatment at Week 52)
Overall survival (OS)	OS is defined as the time between the first administration of IMP (C1D1) and death due to any cause.	Baseline until disease progression (up to the end of treatment at Week 52)
Assessment of pharmacokinetic (PK) parameters: AUC0-t	Area under the plasma concentration versus time curve calculated using the trapezoidal method during a dosing interval (t)	Baseline to 28 days post last dose
Assessment of PK parameters: Cmax	Maximum observed plasma concentration	Baseline to 28 days post last dose
Assessment of PK parameters: Tmax	Time to reach Cmax	Baseline to 28 days post last dose
Assessment of PK parameters: terminal elimination half-life	Time for the concentration to decrease in half	Baseline to 28 days post last dose
Incidence of anti-drug antibodies (ADAs)	Incidence of anti-drug antibodies (ADAs) against SAR448501/DR-0201	Baseline to 28 days post last dose

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Novotech (Australia) Pty Limited
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2024
• Primary Completion (Estimated): January 21, 2028
• Study Completion (Estimated): February 11, 2028

Study Registration Dates

• First Submitted: April 23, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: NHL; Non-Hodgkin Lymphoma; B-NHL
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell
• Other Study ID Numbers: DR-0201-ONC-001; DR0201ONC001 (Other Identifier: Sanofi Identifier); U1111-1328-7660 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No