Description:
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 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.
Title
- Brief Title: A Study of Isatuximab-based Therapy in Participants With Lymphoma
- Official Title: A Phase 1/2 Open-label, Multi-center, Safety, Preliminary Efficacy and Pharmacokinetic (PK) Study of Isatuximab in Combination With Other Anti-cancer Therapies in Participants With Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
ACT15320
- SECONDARY ID:
2018-002442-37
- SECONDARY ID:
U1111-1211-9010
- NCT ID:
NCT03769181
Conditions
Interventions
Drug | Synonyms | Arms |
---|
isatuximab SAR650984 | Sarclisa | Phase 1: cHl/DLBCL/PTCL |
cemiplimab REGN2810 | | Phase 1: cHl/DLBCL/PTCL |
Purpose
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 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.
Detailed Description
The total study duration per patient is 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1: cHl/DLBCL/PTCL | Experimental | Isatuximab dose 1 or 2 depending on dose limiting toxicities (DLTs) observed and cemiplimab predefined dose | - isatuximab SAR650984
- cemiplimab REGN2810
|
Phase 2: Cohort A1: cHL, anti PD-1/PD-L1 naïve | Experimental | Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose | - isatuximab SAR650984
- cemiplimab REGN2810
|
Phase 2: Cohort A2: cHL, anti PD-1/PD-L1 progressor | Experimental | Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose | - isatuximab SAR650984
- cemiplimab REGN2810
|
Phase 2: Cohort B: DLBCL, anti PD-1/PD-L1 naïve | Experimental | Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose | - isatuximab SAR650984
- cemiplimab REGN2810
|
Phase 2: Cohort C: PTCL, anti PD-1/PD-L1 naïve | Experimental | Isatuximab and cemiplimab combination: Isatuximab dose determined in Phase 1 part of study and cemiplimab predefined dose | - isatuximab SAR650984
- cemiplimab REGN2810
|
Eligibility 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
vedotin (BV)
- For Cohort A2 (cHL anti-PD-1/PD-L1 inhibitor progressor): Histologically confirmed
advanced cHL which has 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 (IMP)
- 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 <18 years
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
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 12 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Phase 1 - Dose limiting toxicities (DLTs); Recommended Phase 2 dose (RP2D) |
Time Frame: | 1st Cycle - 28 days |
Safety Issue: | |
Description: | DLTs as observed during DLT-observation period; Dose selected for the Phase 2 portion |
Secondary Outcome Measures
Measure: | Adverse Events (AEs)/Serious Adverse Events (SAEs) for isatuximab + cemiplimab |
Time Frame: | Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration) |
Safety Issue: | |
Description: | Number of patients with AEs/SAEs |
Measure: | Adverse Events/Serious Adverse Events for isatuximab + cemiplimab + radiotherapy |
Time Frame: | Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration) |
Safety Issue: | |
Description: | Number of patients with AEs/SAEs in cohorts A1 and A2 |
Measure: | Immunogenicity: Anti-drug antibody levels |
Time Frame: | Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first |
Safety Issue: | |
Description: | Anti-drug antibody (ADA) levels against isatuximab and against cemiplimab |
Measure: | Pharmacokinetic evaluation: Cmax |
Time Frame: | Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first |
Safety Issue: | |
Description: | Maximum concentration observed after the first infusion |
Measure: | Pharmacokinetic evaluation: Ctrough |
Time Frame: | Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first |
Safety Issue: | |
Description: | Concentrations observed just before treatment administration during repeated dosing |
Measure: | Pharmacokinetic evaluation: AUC0-T |
Time Frame: | Up to 90 days following the last administration of study treatment or at the primary analysis cut-of date, whichever comes first |
Safety Issue: | |
Description: | Area under the concentration versus time curve calculated using the trapezoidal method over the dosing interval (ie, 6 days for isatuximab or 21 days for cemiplimab) |
Measure: | Tumor burden change |
Time Frame: | Up to 24 weeks after last patient treated in a given cohort |
Safety Issue: | |
Description: | The best percent-change from baseline |
Measure: | Disease control rate |
Time Frame: | Up to 24 weeks after last patient treated in a given cohort |
Safety Issue: | |
Description: | The sum of complete responses (CR) + partial responses (PR) + stable disease (SD) |
Measure: | Duration of response |
Time Frame: | Up to 24 weeks after last patient treated in a given cohort |
Safety Issue: | |
Description: | 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 |
Measure: | Progression free survival |
Time Frame: | Up to 24 weeks after last patient treated in a given cohort |
Safety Issue: | |
Description: | The time from the first study treatment administration to the date of first documentation of progressive disease or death, whichever comes first |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Sanofi |
Trial Keywords
- Anti-CD38 monoclonal antibody
Last Updated
July 27, 2021