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.
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.
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.
Sequential
SAR448501
DrugBispecific antibody
Incidence of treatment-emergent adverse event (TEAE)
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
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).
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).
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.
Complete response/remission rate (CRR)
Proportion of participants who have a complete response/remission, based on the disease assessments by the Investigator.
