A Study of Isatuximab-based Therapy in Participants With Lymphoma

Sanofi

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Lymphoma

Treatments: Drug: isatuximab SAR650984; Drug: cemiplimab REGN2810

Study type: Interventional

Funder types: Industry

Identifiers

NCT03769181

2018-002442-37 (EudraCT Number)

ACT15320

U1111-1211-9010 (Registry Identifier)

Details and patient eligibility

About

Primary Objectives:

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] naïve 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 Objectives:

• 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 participants 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.

Full description

The total study duration per participant was up to 28 months, including an up to 28-day screening period, an up to 96-week treatment period, and a 90-day safety follow up period.

Enrollment: 58 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants greater than or equal to (>=) 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 (cHL anti-programmed cell death protein 1/ligand 1 [PD-1/PD-L1] inhibitor naïve): Histologically confirmed advanced cHL that had relapsed or progressed after at least 3 lines of systemic therapy that included autologous hematopoietic stem cell transplant (auto-HSCT) or auto-HSCT and brentuximab vedotin (BV).
• For Cohort A2 (cHL anti-PD-1/PD-L1 inhibitor progressor): Histologically confirmed advanced cHL which had relapsed or progressed after one previous anti-PD-1/PD-L1 containing regimen as the most recent prior therapy but no more than 4 lines of previous chemotherapy including the anti-PD-1/PD-L1 containing regimen and documentation of benefit during or after the anti-PD-1/PD-L1 containing regimen within 4 months prior to initiation of investigational medicinal product.
• For Cohort B (diffuse large B-cell lymphoma [DLBCL]): Histologically confirmed advanced DLBCL that had relapsed or progressed after 2 lines of systemic therapy including auto-HSCT or 2 lines of systemic therapy for participants who were not eligible for auto-HSCT.
• For Cohort C (peripheral T-cell lymphoma [PTCL]): Histologically confirmed advanced PTCL that had relapsed or progressed after either first-line chemotherapy and auto-HSCT as consolidation of first remission or first-line chemotherapy if participants were ineligible for auto-HSCT.
• Body weight of greater than (>) 45 kilograms for participants with age less than (<)18 years.

Exclusion criteria

• Prior exposure to agent that blocks CD38.
• For participants 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, cytotic T-lymphocyte-associated protein 4 or LAG-3.
• Evidence of other immune related disease/conditions.
• Had 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.

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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58 participants in 4 patient groups

Cohort A1: cHL: Isatuximab + Cemiplimab

Experimental group

Description:

Classic Hodgkin's lymphoma (cHL), anti-programmed cell death protein 1/ligand 1 (PD-1/PD-L1) inhibitor naïve participants received isatuximab 10 milligrams per kilogram (mg/kg), intravenous (IV) infusion once a week (QW) in Cycle 1 and then every 2 weeks (Q2W) from Cycle 2 to Cycle 6 (each cycle of 28 days), and then every 3 weeks (Q3W) from Cycle 7 to Cycle 30 (each cycle of 21 days) along with cemiplimab 250 milligrams (mg) Q2W, IV infusion from Cycle 1 to 6 and then 350 mg Q3W from Cycle 7 to Cycle 30, with optional radiotherapy until, unacceptable adverse events (AEs) or participant's decision to stop the treatment, or at least 96 weeks (at least 48 weeks from initial signal of complete response \[CR\], whichever was longer) of delivery of investigational medicinal product(s) without documented progressive disease (PD), or study cut-off date, whichever occurs first (maximum duration: up to 103 weeks).

Treatment:

Drug: cemiplimab REGN2810

Drug: isatuximab SAR650984

Cohort A2: cHL: Isatuximab + Cemiplimab

Experimental group

Description:

cHL, anti-PD-1/PD-L1 inhibitor progressor participants received isatuximab 10 mg/kg, IV infusion, QW in Cycle 1 and then Q2W from Cycle 2 to Cycle 6 (each cycle of 28 days) and Q3W from Cycle 7 to Cycle 30 (each cycle of 21 days) along with cemiplimab 250 mg Q2W, IV infusion from Cycle 1 to 6 and then 350 mg Q3W from Cycle 7 to Cycle 30, with optional radiotherapy until, unacceptable AEs or participant's decision to stop the treatment, or at least 96 weeks (at least 48 weeks from initial signal of CR, whichever was longer) of delivery of investigational medicinal product(s) without documented PD, or study cut-off date, whichever occurs first (maximum duration: up to 103 weeks).

Treatment:

Drug: cemiplimab REGN2810

Drug: isatuximab SAR650984

Cohort B: DLBCL: Isatuximab + Cemiplimab

Experimental group

Description:

Diffuse large B-cell lymphoma (DLBCL), anti PD-1/PD-L1 naïve participants received isatuximab 10 mg/kg, IV infusion, QW in Cycle 1 and then Q2W from Cycle 2 to Cycle 6 (each cycle of 28 days) and Q3W from Cycle 7 to Cycle 30 (each cycle of 21 days) along with cemiplimab 250 mg Q2W, IV infusion from Cycle 1 to 6 and then 350 mg Q3W from Cycle 7 to Cycle 30 until, unacceptable AEs or participant's decision to stop the treatment, or at least 96 weeks (at least 48 weeks from initial signal of CR, whichever was longer) of delivery of investigational medicinal product(s) without documented PD, or study cut-off date, whichever occurs first (maximum duration: up to 103 weeks).

Treatment:

Drug: cemiplimab REGN2810

Drug: isatuximab SAR650984

Cohort C: PTCL: Isatuximab + Cemiplimab

Experimental group

Description:

Peripheral T-cell lymphoma (PTCL), anti PD-1/PD-L1 naïve participants received isatuximab 10 mg/kg, IV infusion, QW in Cycle 1 and then Q2W from Cycle 2 to Cycle 6 (each cycle of 28 days) and Q3W from Cycle 7 to Cycle 30 (each cycle of 21 days) along with cemiplimab 250 mg Q2W, IV infusion from Cycle 1 to 6 and then 350 mg Q3W from Cycle 7 to Cycle 30 until, unacceptable AEs or participant's decision to stop the treatment, or at least 96 weeks (at least 48 weeks from initial signal of CR, whichever was longer) of delivery of investigational medicinal product(s) without documented PD, or study cut-off date, whichever occurs first (maximum duration: up to 103 weeks).

Treatment:

Drug: cemiplimab REGN2810

Drug: isatuximab SAR650984