A Study of Isatuximab-based Therapy in Participants With Lymphoma

NCT03769181 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: ACT153202018-002442-37U1111-1211-9010
• Study Type: interventional
• Target: 58
• Locations: 7 countries
• Sites: 20

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.

Conditions

Lymphoma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLTs: Adverse Events (AEs) occurring during 1st treatment cycle, unless due to disease progression or obviously unrelated cause which included: hematological abnormalities: Grade(G) 4 neutropenia(N) for 7 or more consecutive days, G3 to G4 N with fever (temperature greater than or equal to \[\>=\] 38.5 degree Celsius on more than 1 occasion) or microbiologically/radiographically documented infection, G3 to G4 thrombocytopenia with clinically significant bleeding requiring clinical intervention or non-hematological abnormalities: G 4 non-hematologic AE, G\>=2 uveitis, G3 non-hematological AE lasting greater than (\>)3 days, delay in initiation of Cycle 2 \>14 days due to treatment related laboratory abnormalities/AE. Any other AE that the study committee deemed to be dose-limiting, regardless of grade, was also considered as DLT.

  Cycle 1 (28 days)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)

  An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (defined as the time from the first dose of study treatment up to 30 days after the last dose of study treatment).

  From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)

• Number of Participants With Laboratory Abnormalities: Hematological Parameters

  Hematological parameters assessed were anemia, white blood cell (WBC) decreased, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased. Abnormality criteria was assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 NCI-CTCAE v 5.0), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

  From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)

• Number of Participants With Laboratory Abnormalities: Electrolytes

  Electrolyte parameters assessed were hyponatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypoalbuminemia, hypoglycemia and hyperglycemia. Abnormal criteria was assessed as per the NCI-CTCAE v 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

  From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)

• Number of Participants With Laboratory Abnormalities: Renal Parameters

  Abnormal renal parameters assessed were glomerular filtration rate (GFR) by class, creatinine increased and hyperuricemia. GFR by class was assessed in categories:\>=90 milliliter per minute per 1.73 meter square (mL/min/1.73m\^2) (Normal), \>=60 to \<90 mL/min/1.73m\^2 (Mild), \>=30 to \<60 mL/min/1.73m\^2 (Moderate), \>=15 to \<30 mL/min/1.73m\^2 (Severe), and \<15 mL/min/1.73m\^2 (End Stage Renal Disease). Abnormal criteria was assessed as per NCI-CTCAE v 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

  From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)

• Number of Participants With Laboratory Abnormalities: Liver Function Parameters

  Abnormal liver function parameters assessed were aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, blood bilirubin (BB) increased. Abnormal criteria was assessed as per NCI-CTCAE v 5.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

  From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)

• Cohort A1: Percentage of Participants With Complete Response (CR)

  Percentage of participants who had a CR as a best overall response (BOR) using the Lugano response criteria (LRC) 2014 (based on PET-CT and CT responses). Per LRC, CR based on PET-CT response was defined as complete metabolic response (MR) in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 5-point scale (5PS), where, 1= no uptake above background; 2 = uptake \<=mediastinum; 3 = uptake \> mediastinum but \<= liver; 4 = uptake moderately \> liver; 5 = uptake markedly higher than liver and/or new lesions; no new lesions and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow. CR based on CT-response was defined as target nodes/nodal masses of lymph nodes, extralymphatic sites regressed to \<=1.5 cm in longest dimension transverse diameter of lesion (LDi); absence of non-measured lesion; organ enlargement regressed to normal; no new lesions; normal bone marrow morphology; if indeterminate, immunohistochemistry negative.

  From the date of randomization until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 103 weeks)

• Cohort A2, B and C: Percentage of Participants With Objective Response (OR)

  Percentage of participants who had a CR or partial response (PR) as BOR using LRC, 2014. Per LRC, CR (PET-CT): complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass; no new lesions and no evidence of FDG-avid disease. CR (CT-response): target nodes/nodal masses of lymph nodes, extralymphatic sites regressed to \<=1.5cm LDi; absence of non-measured lesion; organ enlargement regressed to normal; no new lesions; normal bone marrow morphology. PR (PET-CT): partial MR in lymph nodes and extralymphatic sites; no new lesions and residual uptake higher than uptake. PR (Per CT): lymph nodes, extralymphatic sites\>=50% decrease in sum of product of perpendicular diameters (SPD), extranodal sites; if lesion is too small to measure on CT,assign5mm\*5mm as default; if no longer visible:0\*0mm; Node\>5mm\*5mm but smaller than normal, use actual measurement; absent/regressed non-measured lesions; no increase; spleen regressed by\>50% or no new lesions.

  From the date of randomization until disease progression, or death or study cut-off date, whichever comes first (maximum duration: up to 103 weeks)

Secondary Outcomes (25)

• Number of Participants With Treatment-Induced and Treatment Boosted Antidrug Antibodies (ADA) Against Isatuximab

  From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)

• Number of Participants With Treatment-Induced and Treatment Boosted Antidrug Antibodies (ADA) Against Cemiplimab

  From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)

• Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI)

  End of infusion (EOI up to 3 hours) on Day 2 of Cycle 1

• PK Parameter: Maximum Observed Plasma Concentration (Cmax) After the First Infusion of Isatuximab

  At Start of infusion (SOI; 0 hour), before actual EOI (up to 3 hours), EOI+ 4 hours, 72 hours and 144 hours post-dose on Day 2 of Cycle 1

• PK Parameter: Time to Reach Cmax (Tmax) After the First Infusion of Isatuximab

  At SOI (0 hour), before actual EOI (up to 3 hours), EOI+ 4 hours, 72 hours and 144 hours post-dose on Day 2 of Cycle 1

Study Arms (4)

Cohort A1: cHL: Isatuximab + Cemiplimab

EXPERIMENTAL

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).

Drug: isatuximab SAR650984; Drug: cemiplimab REGN2810

Cohort A2: cHL: Isatuximab + Cemiplimab

EXPERIMENTAL

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).

Drug: isatuximab SAR650984; Drug: cemiplimab REGN2810

Cohort B: DLBCL: Isatuximab + Cemiplimab

EXPERIMENTAL

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).

Drug: isatuximab SAR650984; Drug: cemiplimab REGN2810

Cohort C: PTCL: Isatuximab + Cemiplimab

EXPERIMENTAL

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).

Drug: isatuximab SAR650984; Drug: cemiplimab REGN2810

Interventions

isatuximab SAR650984 DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Also known as: Sarclisa

Cohort A1: cHL: Isatuximab + Cemiplimab; Cohort A2: cHL: Isatuximab + Cemiplimab; Cohort B: DLBCL: Isatuximab + Cemiplimab; Cohort C: PTCL: Isatuximab + Cemiplimab

cemiplimab REGN2810 DRUG

Pharmaceutical form: solution for infusion Route of administration: intravenous

Cohort A1: cHL: Isatuximab + Cemiplimab; Cohort A2: cHL: Isatuximab + Cemiplimab; Cohort B: DLBCL: Isatuximab + Cemiplimab; Cohort C: PTCL: Isatuximab + Cemiplimab

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (20)

Investigational Site Number :2500005

Dijon, 21000, France

Location

Investigational Site Number :2500004

Montpellier, 34295, France

Location

Investigational Site Number :2500002

Nantes, 44093, France

Location

Investigational Site Number :2500007

Pessac, 33600, France

Location

Investigational Site Number :2500001

Villejuif, 94800, France

Location

Investigational Site Number :3800003

Rozzano, Milano, 20089, Italy

Location

Investigational Site Number :3800002

Bologna, 40138, Italy

Location

Investigational Site Number :3800006

Brescia, 25123, Italy

Location

Investigational Site Number :5280002

Amsterdam, 1081 HV, Netherlands

Location

Investigational Site Number :5280001

Maastricht, 6229 HX, Netherlands

Location

Investigational Site Number :6200002

Coimbra, 3000-075, Portugal

Location

Investigational Site Number :6200004

Lisbon, 1649-035, Portugal

Location

Investigational Site Number :6200003

Porto, 4200, Portugal

Location

Investigational Site Number :4100001

Gangnam-gu, Seoul-teukbyeolsi, 06351, South Korea

Location

Investigational Site Number :4100002

Seoul, Seoul-teukbyeolsi, 03080, South Korea

Location

Investigational Site Number :7240003

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number :7240005

Barcelona, Barcelona [Barcelona], 08036, Spain

Location

Investigational Site Number :7240002

L'Hospitalet de Llobregat, Barcelona [Barcelona], 08908, Spain

Location

Investigational Site Number :7240004

Madrid / Madrid, Madrid, Comunidad de, 28040, Spain

Location

Investigational Site Number :1580002

Taichung, 40447, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 36251503 BACKGROUND

Related Links

• ACT15320 Plain Language Results Summary

MeSH Terms

Conditions

Lymphoma

Interventions

isatuximab; cemiplimab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The efficacy results observed in Cohorts B and C did not fulfill the pre-planned interim analysis criteria allowing the study to move to Phase 2 Stage 2 in these cohorts. The efficacy results observed in Cohort A1 and A2 fulfilled the pre-planned interim analysis criteria in Stage 1 to move to Phase 2 Stage 2 in these cohorts. However, the study was stopped for all the cohorts as per Sponsor's decision.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Aventis Recherche & Développement

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2018
• First Posted: December 7, 2018
• Study Start: December 11, 2018
• Primary Completion: November 8, 2022
• Study Completion: November 8, 2022
• Last Updated: September 23, 2025
• Results First Posted: October 17, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

NL (2); IT (3); PT (3); FR (5); KR (2); ES (4); TW (1)