Lymphoma MedDRA version: 20.0 Level: PT Classification code 10025310 Term: Lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Sanofi-aventis recherche & developpement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Participants must be = 12 years of age inclusive, at the time of signing the informed consent - Disease location amenable to tumor biopsy at baseline - Measurable disease - For Cohort A1 (classic Hodgkin's lymphoma [cHL] anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] inhibitor naïve): Histologically confirmed advanced cHL that has relapsed or progressed after at least 3 lines of systemic therapy that may include autologous hematopoietic stem cell transplant (auto-HSCT) or auto-HSCT and brentuximab vedontin (BV) -Cohort A2: classic Hodgkin’s lymphoma with documentation of benefit but subsequent progression during or after the prior anti-PD1/PD-L1 containing regimen. Progression has to occur within 6 months from last dose of the prior anti-PD1/PD-L1 containing regimen - For Cohort B (diffuse large B-cell lymphoma [DLBCL]):Histologically confirmed advanced DLBCL that has relapsed or progressed after 2 lines of systemic therapy including auto-HSCT or 2 lines of systemic therapy for participants who are not eligible for auto-HSCT - For Cohort C (peripheral T-cell lymphoma [PTCL]): Histologically confirmed advanced PTCL that has relapsed or progressed after either first-line chemotherapy and auto-HSCT as consolidation of first remission or first-line chemotherapy if participants are ineligible for auto-HSCT - Body weight of > 45 kg for patients with age =65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: -Prior exposure to agent that blocks CD38 - For patients with cHL (PD-1/PD-L1 naïve), DLBCL or PTCL prior exposure to any agent (approved or investigational) that blocks the PD-1/PD-L1, PD-L2, CD137, CTLA-4 or LAG-3 - Evidence of other immune related disease /conditions - Has received a live-virus vaccination within 28 days of planned treatment start; seasonal flu vaccines that do not contain live virus are permitted - Eastern Cooperative Oncology Group (ECOG) performance status (PS) =2 - Poor bone marrow reserve - Poor organ function
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1 -To characterize the safety and tolerability of isatuximab in combination with cemiplimab in participants with relapsed and refractory classic Hodgkin’s lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma (PTCL), and to confirm the recommended Phase 2 dose (RP2D). Phase 2 - Cohort A1 (anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] naive cHL): To assess the complete remission (CR) rate of isatuximab in combination with cemiplimab. - Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): To assess the objective response rate (ORR) of isatuximab in combination with cemiplimab.;Secondary Objective: - To evaluate the safety of the RP2D of the combination of isatuximab with cemiplimab. - To evaluate the safety of the combination of isatuximab with cemiplimab and radiotherapy in patients with cHL. - To evaluate the immunogenicity of isatuximab and cemiplimab when given in combination. - To characterize the pharmacokinetic (PK) profile of isatuximab and cemiplimab when given in combination. -To assess overall efficacy of isatuximab in combination with cemiplimab and isatuximab in combination with cemiplimab and radiotherapy.;Primary end point(s): Phase 1 1) Dose limiting toxicities (DLTs): DLTs as observed during DLT-observation period 2) Recommended Phase 2 dose (RP2D): Dose selected for the Phase 2 portion Phase 2 3) Cohort A1 (anti-PD-1/PD-L1 naive cHL): Complete Remission Rate: The proportion of participants who have a Complete Remission as a best overall response during the isatuximab + cemiplimab therapy period using the Lugano response criteria 2014 4) Cohort A2 (cHL progressing from PD-1/PD-L1), B (DLBCL) and C (PTCL): Response Rate : The proportion of participants who have a Complete Response or Partial Response as a best overall response during isatuximab + cemiplimab therapy period using the Lugano response criteria 2014 ;Timepoint(s) of evaluation of this end point: 1) and 2) 1st | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Adverse Events (AEs)/Serious Adverse Events (SAEs) for isatuximab + cemiplimab: Number of patients with AEs/SAEs 2) Adverse Events/Serious Adverse Events for isatuximab + cemiplimab + radiotherapy: Number of patients with AEs/SAEs in cohorts A1 and A2 3) Immunogenicity: Anti-drug antibody (ADA) levels against isatuximab and against cemiplimab 4) Pharmacokinetic evaluation: Pharmacokinetic evaluation using non-compartmental analysis for both compounds using serum concentrations for cemiplimab and plasma concentrations for isatuximab 5) Tumor burden change: The best percent-change from baseline 6) Disease control rate: The sum of complete responses (CR) + partial responses (PR) + stable disease (SD) 7) Duration of response: The time from the date of the first response (PR or CR in radiographic objective response) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first. 8) Progression free survival: The time from the first study treatment administration to the date of first documentation of progressive disease or death, whichever comes first.;Timepoint(s) of evaluation of this end point: 1) to 4) Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration) 5) to 8) Up to 24 weeks after last patient treated in a given cohort | — |
Countries
France, Italy, Korea, Republic of, Netherlands, Portugal, Spain, Taiwan
Contacts
Public ContactTeam Manager
Genzyme Europe B.V.
Outcome results
None listed