LymphomaPhase 1/2NCT03769181
A Study of Isatuximab-based Therapy in Participants With Lymphoma
A Phase 1/2 study testing isatuximab SAR650984 and cemiplimab REGN2810 in people with Lymphoma, run by Sanofi at 20 sites in 7 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- isatuximab SAR650984 and cemiplimab REGN2810
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 20 sitesin 7 countries
- Study dates
- 11 Dec 2018to 8 Nov 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
France5 sites
Investigational Site Number :2500005
Dijon, 21000
Investigational Site Number :2500004
Montpellier, 34295
Investigational Site Number :2500002
Nantes, 44093
Investigational Site Number :2500007
Pessac, 33600
Investigational Site Number :2500001
Villejuif, 94800
Spain4 sites
Investigational Site Number :7240003
Barcelona, Barcelona [Barcelona], 08035
Investigational Site Number :7240005
Barcelona, Barcelona [Barcelona], 08036
Investigational Site Number :7240002
L'Hospitalet de Llobregat, Barcelona [Barcelona], 08908
Investigational Site Number :7240004
Madrid / Madrid, Madrid, Comunidad de, 28040
Italy3 sites
Investigational Site Number :3800002
Bologna, 40138
Investigational Site Number :3800006
Brescia, 25123
Investigational Site Number :3800003
Rozzano, Milano, 20089
Portugal3 sites
Investigational Site Number :6200002
Coimbra, 3000-075
Investigational Site Number :6200004
Lisbon, 1649-035
Investigational Site Number :6200003
Porto, 4200
Netherlands2 sites
Investigational Site Number :5280002
Amsterdam, 1081 HV
Investigational Site Number :5280001
Maastricht, 6229 HX
South Korea2 sites
Investigational Site Number :4100001
Gangnam-gu, Seoul-teukbyeolsi, 06351
Investigational Site Number :4100002
Seoul, Seoul-teukbyeolsi, 03080
About this study
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
Primary Objectives:
Phase 1
Read more
-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.
Read the 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
- Being tested
- isatuximab SAR650984, cemiplimab REGN2810
- Keywords
- Anti-CD38 monoclonal antibody
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
isatuximab SAR650984Drug
Also called Sarclisa
Pharmaceutical form: solution for infusion
Route of administration: intravenous
cemiplimab REGN2810Drug
Pharmaceutical form: solution for infusion
Route of administration: intravenous
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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). Receives: 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). Receives: Drug: isatuximab SAR650984; Drug: cemiplimab REGN2810 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
ADA responses were categorized as treatment boosted ADA and treatment-induced ADA. Treatment boosted ADA was defined as pre-existing ADAs with a significant increase in the ADA titer during the study compared to the Baseline titer. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without pre-existing ADA.
Measured: 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
ADA responses were categorized as treatment boosted ADA and treatment-induced ADA. Treatment boosted ADA was defined as pre-existing ADAs with a significant increase in the ADA titer during the study compared to the Baseline titer. Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without pre-existing ADA.
Measured: 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)
Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.
Measured: 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
Cmax was defined as the maximum plasma concentration observed after the first administration of drug.
Measured: 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
Tmax was defined as the time to reach Cmax, after the intravenous infusion of isatuximab.
Measured: 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
PK Parameter: Area Under the Plasma Concentration (AUClast) Versus Time Curve After the First Infusion of Isatuximab
AUClast was defined as area under the plasma concentration versus time curve calculated from time 0 to last quantifiable concentration, calculated for isatuximab.
Measured: 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
PK Parameter: Last Concentration Observed Above the Lower Limit of Quantification (Clast) After the First Infusion of Isatuximab
Clast was defined as the last concentration of isatuximab observed above the lower limit of quantification.
Measured: 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
PK Parameter: Time of Clast (Tlast) After the First Infusion of Isatuximab
Tlast was defined as the time of last concentration observed above the lower limit of quantification for isatuximab.
Measured: 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
PK Parameter: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUC0-168 Hours) After the First Infusion of Isatuximab
AUC0-168 hours was defined as the area under the plasma concentration versus time curve from time 0 to 168 hours post dose calculated for isatuximab. Samples for this outcome measure were collected up to 144 hours post-dose. No sample was collected at 168 hours post-dose; and thus, the samples collected up to 144 hours post-dose were extrapolated to derive data for 168 hours post-dose.
Measured: 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
PK Parameter: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUC0-144 Hours) After the First Infusion of Isatuximab
AUC0-144 hours was defined as the area under the plasma concentration versus time curve from time 0 to 144 hours post dose calculated for isatuximab.
Measured: 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
PK Parameter: Plasma Trough Concentration (Ctrough) of Isatuximab
Ctrough was the plasma concentration of isatuximab observed just before treatment administration during repeated dosing.
Measured: Pre-infusion on Cycle1:Day 2, 8, 15, & 22, Cycle 2:Day 1 &15, Cycle 3:Day 1 &15, Cycle 4:Day 1 &15, Cycle 5 Day1,Cycle 6 Day1,Cycle 7 Day 1, Cycle 8 Day1, Cycle 9 Day1, Cycle 10 Day1, Cycle 11 Day1, Cycle14 Day1, Cycle 17 Day1, Cycle 20 Day1,Cycle 23 Day1
PK Parameter: Serum Concentration of Cemiplimab at End of Infusion (CEOI)
Ceoi is the plasma concentration observed at the end of intravenous infusion of cemiplimab.
Measured: EOI (up to 30 minutes [min]) on Day 1 of Cycle 1
PK Parameter: Maximum Observed Concentration (Cmax) After the First Infusion of Cemiplimab
Cmax was defined as the maximum concentration observed after the first administration.
Measured: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Time to Reach Cmax (Tmax) After the First Infusion of Cemiplimab
Tmax was defined as the time to reach Cmax after the intravenous infusion of cemiplimab.
Measured: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Area Under the Serum Concentration (AUClast) Versus Time Curve After the First Infusion of Cemiplimab
AUClast was defined as area under the serum concentration versus time curve calculated from time 0 to last quantifiable concentration calculated for cemiplimab.
Measured: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Last Concentration Observed Above the Lower Limit of Quantification (Clast) After the First Infusion of Cemiplimab
Clast was defined as the last concentration of cemiplimab observed above the lower limit of quantification.
Measured: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Time of Clast (Tlast) After the First Infusion of Cemiplimab
Tlast was defined as the time of last concentration observed above the lower limit of quantification for cemiplimab.
Measured: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Area Under the Serum Concentration Versus Time Curve Over the Dosing Interval (AUC0-336 Hours) After the First Infusion of Cemiplimab
AUC0-336 hours was defined as the area under the serum concentration versus time curve from time 0 to 336 hours post dose for cemiplimab.
Measured: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Serum Trough Concentration (Ctrough) of Cemiplimab
Ctrough was the serum concentration of cemiplimab observed just before treatment administration during repeated dosing.
Measured: Pre-infusion on Cycle 1:Day 1 & Day15,Cycle 2:Day 1 & Day 15,Cycle 3:Day 1 & Day 15,Cycle 4:Day 1 & Day15,Cycle 5 Day 1,Cycle 6 Day 1,Cycle7 Day1,Cycle 8 Day 1,Cycle 9 Day1,Cycle 10 Day1,Cycle11 Day1,Cycle14 Day 1,Cycle 17 Day1,Cycle20 Day 1,Cycle 23 Day1
Percent Change From Baseline in Tumor Burden
Tumor burden change was defined as the best percent-change from baseline in a sum of product of lesion diameters (longest for non-nodal lesion, short axis for nodal lesions) for all target lesions.
Measured: Up to 103 weeks
Duration of Response (DOR)
Time (months) between date of first response to first date that recurrent or radiologically disease progression (PD) was documented, or date of death,whichever was 1st. In absence of PD or death before cut-off date or date of initiation of further anticancer treatment, DOR was censored at date of last valid response not showing PD performed prior to initiation of further anticancer treatment or cut-off date, whichever was earlier. PD(PET-CT): metabolic disease with score 4/5 with inc. in intensity of uptake for target nodes/nodal mass \& new FDG-avid foci consistent with lymphoma. PD(CT):any 1 of following: cross product of longest transverse diameter of lesion(LDi) \& perpendicular diameter (PPD) progression of nodes/nodal mass, abnormal node/lesion with LDi >1.5 cm, inc >=50% from PPD nadir \& inc in LDi/ shortest axis perpendicular to LDi(SDi) from nadir 0.5 cm, regrowth of resolved lesions, new splenomegaly,progression of non-measured lesion, new/recurrent involvement of bone marrow.
Measured: From the date of first response until disease progression or death, or study cut-off date whichever occurred first (maximum duration: up to 103 weeks)
Percentage of Participants With Disease Control (DC)
DC defined as percentage of participants who achieved CR, PR or stable disease (SD) as per LRC, 2014. CR (PET-CT): complete MR in lymph nodes and extralymphatic sites; no new lesions and no evidence of FDG-avid disease. CR (CT): 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. PR (PET-CT): partial MR in lymph nodes and sites; no new lesions. PR (CT): lymph nodes, sites>=50% decrease in SPD, sites; if lesion is too small to measure on CT, assign 5mm*5mm; No longer visible:0*0mm; Node>5mm*5mm, use actual measurement; absent/regressed non-measured lesions; no increase; spleen regressed by>50% or no new lesions. SD (PET-CT):no metabolic response, target nodes score of 4/5 with no significant change \& no new lesions; SD (CT): <50% dec in SPD, no increase in progression for. 5PS:1: non-measured lesions, organ enlargement \& no new lesions.
Measured: From the date of first response until disease progression or death, or study cut-off date whichever occurred first (maximum duration: up to 103 weeks)
Progression Free Survival (PFS)
PFS: time (in months) from 1st study treatment administration to date of 1st documented radiographic progression or date of death from any cause, whichever occurs 1st. Per LRC, 2014 PD (per PET-CT): metabolic disease with score 4/5 with increase (inc) in intensity of uptake for individual target nodes/nodal mass \& new FDG-avid foci consistent with lymphoma at interim/ end-of-treatment assessment for extra nodal lesions, new FDG-avid foci consistent with lymphoma rather; new/recurrent FDG-avid foci bone marrow. PD (per CT response): any 1 of following: cross product of longest transverse diameter of lesion (LDi) \& perpendicular diameter (PPD) progression of nodes/nodal mass, abnormal node/lesion with LDi >1.5 cm, inc >=50% from PPD nadir \& inc in LDi/ shortest axis perpendicular to LDi from nadir 0.5 cm for lesion <= 2 cm, regrowth of resolved lesions, new splenomegaly,progression of preexisting non measured lesion, new/recurrent involvement of bone marrow.
Measured: 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 A1 and A2: Percentage of Participants With Objective Response
Percentage of participants who had a CR or PR as BOR using LRC, 2014 (based on PET-CT and CT responses). CR (per PET-CT): complete MR in lymph nodes and extra lymphatic 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 (per PET-CT): partial MR in lymph nodes and extral ymphatic sites; no new lesions and residual uptake higher than uptake. PR (per CT): lymph nodes, extralymphatic sites >=50% decrease in SPD, extranodal sites; if lesion is too small to measure on CT, assign 5mm*5mm as default; if no longer visible:0*0mm; Node>5mm*5mm but smaller than normal, used actual measurement; absent/regressed non-measured lesions; no increase; spleen regressed by>50% or no new lesions.
Measured: 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 A1 and A2: Percentage of Participants With Complete Response
Percentage of participants who had a CR as a BOR using the LRC, 2014 (based on PET-CT and CT responses). Per LRC, CR based on PET-CT was defined as complete MR in lymph nodes and extralymphatic sites with a score of 1, 2, or 3 with or without residual mass, on 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 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.
Measured: From the date of randomization until disease progression, or death or study cut-off date, whichever comes first (maximum duration: up to 103 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2018
- Study start11 Dec 2018
- Primary completion8 Nov 2022
- Study completion8 Nov 2022
Why it stopped: Study was stopped after interim analysis for all 4 cohorts with results either not fulfilling the pre-planned interim analysis criteria or fulfilling the criteria but as per sponsor decision. It was not due to any safety concern
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03769181
- Sponsor's protocol ID
- ACT15320
- Other IDs
- 2018-002442-37, U1111-1211-9010, 2018
- Status last verified
- Sep 2025
- First submitted
- 29 Nov 2018
- Last updated
- 23 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Publications
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.
PubMed 36251503
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03769181
- Acronym / sponsor ID
- ACT15320
- Conditions
- Lymphoma
- Keywords
- Anti-CD38 monoclonal antibody
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was stopped after interim analysis for all 4 cohorts with results either not fulfilling the pre-planned interim analysis criteria or fulfilling the criteria but as per sponsor decision. It was not due to any safety concern
- Enrolment
- 58 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- 11 Dec 2018 (actual)
- Primary completion
- 8 Nov 2022 (actual)
- Study completion
- 8 Nov 2022 (actual)
- First posted
- 7 Dec 2018 (actual)
- Results
- Posted 17 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort A1: cHL: Isatuximab + Cemiplimab | Experimental | Drug: isatuximab SAR650984, Drug: cemiplimab REGN2810Classic 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). |
| Cohort A2: cHL: Isatuximab + Cemiplimab | Experimental | Drug: isatuximab SAR650984, Drug: cemiplimab REGN2810cHL, 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). |
| Cohort B: DLBCL: Isatuximab + Cemiplimab | Experimental | Drug: isatuximab SAR650984, Drug: cemiplimab REGN2810Diffuse 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). |
| Cohort C: PTCL: Isatuximab + Cemiplimab | Experimental | Drug: isatuximab SAR650984, Drug: cemiplimab REGN2810Peripheral 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). |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| isatuximab SAR650984Also: SarclisaPharmaceutical form: solution for infusion Route of administration: intravenous | Drug | Cohort A1: cHL: Isatuximab + Cemiplimab, Cohort A2: cHL: Isatuximab + Cemiplimab, Cohort B: DLBCL: Isatuximab + Cemiplimab, Cohort C: PTCL: Isatuximab + Cemiplimab |
| cemiplimab REGN2810Pharmaceutical form: solution for infusion Route of administration: intravenous | Drug | Cohort A1: cHL: Isatuximab + Cemiplimab, Cohort A2: cHL: Isatuximab + Cemiplimab, Cohort B: DLBCL: Isatuximab + Cemiplimab, Cohort C: PTCL: Isatuximab + Cemiplimab |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Cycle 1 (28 days)
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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), and Treatment-Emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)
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).
Number of Participants With Laboratory Abnormalities: Hematological Parameters
Time frame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)
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.
Number of Participants With Laboratory Abnormalities: Electrolytes
Time frame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)
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.
Number of Participants With Laboratory Abnormalities: Renal Parameters
Time frame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)
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.
Number of Participants With Laboratory Abnormalities: Liver Function Parameters
Time frame: From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 103 weeks)
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.
Cohort A1: Percentage of Participants With Complete Response (CR)
Time frame: From the date of randomization until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 103 weeks)
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.
Cohort A2, B and C: Percentage of Participants With Objective Response (OR)
Time frame: From the date of randomization until disease progression, or death or study cut-off date, whichever comes first (maximum duration: up to 103 weeks)
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.
25 secondary outcomes
Number of Participants With Treatment-Induced and Treatment Boosted Antidrug Antibodies (ADA) Against Isatuximab
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
PK Parameter: Area Under the Plasma Concentration (AUClast) Versus Time Curve After the First Infusion of Isatuximab
Time frame: 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
PK Parameter: Last Concentration Observed Above the Lower Limit of Quantification (Clast) After the First Infusion of Isatuximab
Time frame: 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
PK Parameter: Time of Clast (Tlast) After the First Infusion of Isatuximab
Time frame: 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
PK Parameter: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUC0-168 Hours) After the First Infusion of Isatuximab
Time frame: 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
PK Parameter: Area Under the Concentration Versus Time Curve Over the Dosing Interval (AUC0-144 Hours) After the First Infusion of Isatuximab
Time frame: 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
PK Parameter: Plasma Trough Concentration (Ctrough) of Isatuximab
Time frame: Pre-infusion on Cycle1:Day 2, 8, 15, & 22, Cycle 2:Day 1 &15, Cycle 3:Day 1 &15, Cycle 4:Day 1 &15, Cycle 5 Day1,Cycle 6 Day1,Cycle 7 Day 1, Cycle 8 Day1, Cycle 9 Day1, Cycle 10 Day1, Cycle 11 Day1, Cycle14 Day1, Cycle 17 Day1, Cycle 20 Day1,Cycle 23 Day1
PK Parameter: Serum Concentration of Cemiplimab at End of Infusion (CEOI)
Time frame: EOI (up to 30 minutes [min]) on Day 1 of Cycle 1
PK Parameter: Maximum Observed Concentration (Cmax) After the First Infusion of Cemiplimab
Time frame: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Time to Reach Cmax (Tmax) After the First Infusion of Cemiplimab
Time frame: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Area Under the Serum Concentration (AUClast) Versus Time Curve After the First Infusion of Cemiplimab
Time frame: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Last Concentration Observed Above the Lower Limit of Quantification (Clast) After the First Infusion of Cemiplimab
Time frame: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Time of Clast (Tlast) After the First Infusion of Cemiplimab
Time frame: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Area Under the Serum Concentration Versus Time Curve Over the Dosing Interval (AUC0-336 Hours) After the First Infusion of Cemiplimab
Time frame: At SOI (0 hour), before actual EOI (up to 30 min), EOI+4 hours, 96 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1
PK Parameter: Serum Trough Concentration (Ctrough) of Cemiplimab
Time frame: Pre-infusion on Cycle 1:Day 1 & Day15,Cycle 2:Day 1 & Day 15,Cycle 3:Day 1 & Day 15,Cycle 4:Day 1 & Day15,Cycle 5 Day 1,Cycle 6 Day 1,Cycle7 Day1,Cycle 8 Day 1,Cycle 9 Day1,Cycle 10 Day1,Cycle11 Day1,Cycle14 Day 1,Cycle 17 Day1,Cycle20 Day 1,Cycle 23 Day1
Percent Change From Baseline in Tumor Burden
Time frame: Up to 103 weeks
Duration of Response (DOR)
Time frame: From the date of first response until disease progression or death, or study cut-off date whichever occurred first (maximum duration: up to 103 weeks)
Percentage of Participants With Disease Control (DC)
Time frame: From the date of first response until disease progression or death, or study cut-off date whichever occurred first (maximum duration: up to 103 weeks)
Progression Free Survival (PFS)
Time frame: 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 A1 and A2: Percentage of Participants With Objective Response
Time frame: 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 A1 and A2: Percentage of Participants With Complete Response
Time frame: From the date of randomization until disease progression, or death or study cut-off date, whichever comes first (maximum duration: up to 103 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 36251503Carlo-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.
- ACT15320 Plain Language Results SummaryLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing isatuximab SAR650984 and cemiplimab REGN2810 in people with Lymphoma, run by Sanofi at 20 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in France, Spain, Italy, Portugal, Netherlands and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (28 days)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03769181, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2025.