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

Official title

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

Overview

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.

Interventions

• Drug SAR448501
  Bispecific antibody

Primary outcome measures

• Incidence of treatment-emergent adverse event (TEAE) [Time frame: Baseline to 28 days post last dose]
• Potential pharmacologically optimized dose/regimen(s) of SAR448501 / DR-0201 in participants with R/R B-NHL [Time frame: Cycle 1 (Day 1 to Day 28)]

Secondary outcome measures (12)

• Response rate assessed for CLL [Time frame: Baseline until disease progression (up to the end of treatment at Week 52)]
• Response rate assessed for all other B-NHL lymphomas [Time frame: Baseline until disease progression (up to the end of treatment at Week 52)]
• Duration of response/remission (DOR) [Time frame: Baseline until disease progression (up to the end of treatment at Week 52)]
• Complete response/remission rate (CRR) [Time frame: Baseline until the end of treatment (Week 52)]
• Time to response (TTR in months) [Time frame: Baseline until the end of treatment (Week 52)]
• Progression-free survival (PFS) [Time frame: Baseline until disease progression (up to the end of treatment at Week 52)]
• Overall survival (OS) [Time frame: Baseline until disease progression (up to the end of treatment at Week 52)]
• Assessment of pharmacokinetic (PK) parameters: AUC0-t [Time frame: Baseline to 28 days post last dose]
• Assessment of PK parameters: Cmax [Time frame: Baseline to 28 days post last dose]
• Assessment of PK parameters: Tmax [Time frame: Baseline to 28 days post last dose]
• Assessment of PK parameters: terminal elimination half-life [Time frame: Baseline to 28 days post last dose]
• Incidence of anti-drug antibodies (ADAs) [Time frame: Baseline to 28 days post last dose]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 5 centers

• Investigational Site Number : 001-203 — Camperdown
• Investigational Site Number : 001-202 — Townsville
• Investigational Site Number : 001-205 — Adelaide
• Investigational Site Number : 001-204 — Melbourne
• Investigational Site Number : 001-201 — Perth

South Korea · 5 centers

• Investigational Site Number : 001-401 — Busan
• Investigational Site Number : 001-403 — Busan
• Investigational Site Number : 001-404 — Goyang-si
• Investigational Site Number : 001-402 — Seoul
• Investigational Site Number : 001-405 — Seoul

Taiwan · 3 centers

• Investigational Site Number : 001-503 — Changhua
• Investigational Site Number : 001-502 — Kaohsiung City
• Investigational Site Number : 001-501 — Taipei

Singapore · 2 centers

• Investigational Site Number : 001-601 — Singapore
• Investigational Site Number : 001-602 — Singapore

Serbia · 1 center

• Investigational Site Number : 001-703 — Kamenitz

Identifiers

NCT: NCT06392477 · DR-0201-ONC-001 · DR0201ONC001 · U1111-1328-7660

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗