A Study of Isatuximab-based Therapy in Participants With Lymphoma

NCT ID: NCT03769181

Last Updated: 2025-09-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-11
• Study Completion Date: 2022-11-08

Brief Summary

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.

Detailed 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.

Conditions

Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A1: cHL: Isatuximab + Cemiplimab

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).

Group Type: EXPERIMENTAL

isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Cohort A2: cHL: Isatuximab + Cemiplimab

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).

Group Type: EXPERIMENTAL

isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Cohort B: DLBCL: Isatuximab + Cemiplimab

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).

Group Type: EXPERIMENTAL

isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Cohort C: PTCL: Isatuximab + Cemiplimab

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).

Group Type: EXPERIMENTAL

isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

cemiplimab REGN2810

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Interventions

isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Intervention Type: DRUG

cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Intervention Type: DRUG

Other Intervention Names

Sarclisa

Eligibility Criteria

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.

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number :2500005

Dijon, , France

Investigational Site Number :2500004

Montpellier, , France

Investigational Site Number :2500002

Nantes, , France

Investigational Site Number :2500007

Pessac, , France

Investigational Site Number :2500001

Villejuif, , France

Investigational Site Number :3800003

Rozzano, Milano, Italy

Investigational Site Number :3800002

Bologna, , Italy

Investigational Site Number :3800006

Brescia, , Italy

Investigational Site Number :5280002

Amsterdam, , Netherlands

Investigational Site Number :5280001

Maastricht, , Netherlands

Investigational Site Number :6200002

Coimbra, , Portugal

Investigational Site Number :6200004

Lisbon, , Portugal

Investigational Site Number :6200003

Porto, , Portugal

Investigational Site Number :4100001

Gangnam-gu, Seoul-teukbyeolsi, South Korea

Investigational Site Number :4100002

Seoul, Seoul-teukbyeolsi, South Korea

Investigational Site Number :7240003

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number :7240005

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number :7240002

L'Hospitalet de Llobregat, Barcelona [Barcelona], Spain

Investigational Site Number :7240004

Madrid / Madrid, Madrid, Comunidad de, Spain

Investigational Site Number :1580002

Taichung, , Taiwan

Countries

France; Italy; Netherlands; Portugal; South Korea; Spain; Taiwan

References

Carlo-Stella C, Zinzani PL, Sureda A, Araujo L, Casasnovas O, Carpio C, Yeh SP, Bouabdallah K, Cartron G, Kim WS, Cordoba R, Koh Y, Re A, Alves D, Chamuleau M, Le Gouill S, Lopez-Guillermo A, Moreira I, van der Poel MWM, Abbadessa G, Meng R, Ji R, Lepine L, Saleem R, Ribrag V. A phase 1/2, open-label, multicenter study of isatuximab in combination with cemiplimab in patients with lymphoma. Hematol Oncol. 2023 Feb;41(1):108-119. doi: 10.1002/hon.3089. Epub 2022 Oct 31.

Reference Type: BACKGROUND

PMID: 36251503 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.trialsummaries.com/Study/StudyDetails?id=25185&tenant=MT_SNY_9011

ACT15320 Plain Language Results Summary

Other Identifiers

2018-002442-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1211-9010

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACT15320

Identifier Type: -

Identifier Source: org_study_id