Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Cemiplimab

Antineoplastic Agents, Immunological

SAR441000 will be administered as intratumoral injection as monotherapy in patients with solid tumors over a 28-day cycle

SAR441000 will be administered as intratumoral injection in patients with solid tumors in combination with cemiplimab over a 21-day cycle

SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced melanoma who have failed anti-PD-1/PD-L1 therapy. Treatment is administered over a 21-day cycle

SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve melanoma over a 21-day cycle

SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve Cutaneous Squamous Cell Carcinoma (CSCC) over a 21-day cycle

SAR441000 will be administered intratumorally at the determined recommended dose in combination with cemiplimab to patients with advanced anti-PD-1/PD-L1 naïve Head and Neck Squamous Cell Cancer (HNSCC) over a 21-day cycle

Pharmaceutical form: concentrate for solution for injection

Route of administration: intratumoral

SAR441000

Pharmaceutical form: solution for injection

Route of administration: intravenous

Cemiplimab REGN2810

Clinical Sciences & Operations

Primary Objectives:

* Dose Escalation: To determine maximum tolerated dose (MTD) or maximum administered dose (MAD) and overall safety and tolerability profile of SAR441000 when administered intratumorally as monotherapy and in combination with cemiplimab in patients who have no alternative standard treatment options.
* Dose Expansion (Combination): To determine the objective response rate of SAR441000 administered intratumorally in combination with cemiplimab in patients with melanoma, cutaneous squamous cell carcinoma or head and neck squamous cell carcinoma.

Secondary Objectives:

* To characterize the pharmacokinetic (PK) profile of SAR441000 administered as monotherapy and in combination with cemiplimab.
* To assess the immunogenicity of SAR441000.
* To characterize the safety of SAR441000 when administered intratumorally in combination with cemiplimab.
* To determine the disease control rate (DCR), duration of response (DoR) and progression free survival (PFS) of SAR441000.
* To determine the recommended dose of SAR441000 for the expansion phase.

The expected duration of treatment for patients who benefit from study intervention may vary, based on progression date. Median expected duration of study per patient is estimated as 9 months in monotherapy and 12 months in combination therapy.

The maximum treatment duration for non-progressive patients is up to 2 years.

A First-in-Human Dose Escalation and Expansion Study to Evaluate Intratumoral Administration of SAR441000 as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors

A Phase 1 First-in-Human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR441000 Administered Intratumorally as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors

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

Incidence of DLTs at Cycle 1 (SAR441000 monotherapy), assessed as the occurrence of AE, satisfying protocol defined DLT criteria, using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 whether related or not to the study treatment in the absence of clear evidence to the contrary, and if not related to a disease progression

Incidence of DLTs during period from Cycle 1 Day 1 to Cycle 2 Day 8 (SAR441000 + cemiplimab combination therapy), assessed as the occurrence of AE, satisfying protocol defined DLT criteria, using NCI-CTCAE version 5.0 whether related or not to the study treatment in the absence of clear evidence to the contrary, and if not related to a disease progression

MTD of SAR441000 as monotherapy, determined during Cycle 1 of dose escalation phase

MTD of SAR441000, in combination with cemiplimab, determined during period from Cycle 1 Day 1 to Cycle 2 Day 8 in dose escalation phase

Incidence of Treatment Emergent Adverse Events (TEAE) during dose escalation phase

Assessment of overall response rate using standard imaging and RECIST 1.1 criteria

Maximum plasma concentration (Cmax) of SAR4410000 as monotherapy observed over the dosing interval

Maximum plasma concentration (Cmax) of SAR4410000 in combination with cemiplimab observed over the dosing interval

Area under the plasma concentration versus time curve (AUC) of SAR441000 as monotherapy over the dosing interval

Area under the plasma concentration versus time curve (AUC) of SAR441000 in combination with cemiplimab over the dosing interval

Trough Plasma Concentration (Ctrough) of SAR441000 as monotherapy and in combination with cemiplimab. It is defined as plasma concentration observed just before treatment administration during repeated dosing

Maximum plasma concentration of cemiplimab in combination with SAR441000, observed over the dosing interval

Area under the plasma concentration versus time curve of cemiplimab in combination with SAR441000 over the dosing interval

Trough plasma concentration of cemiplimab in combination with SAR441000, observed just before treatment administration during repeated dosing

Incidence of anti-drug antibody (ADA) positive patients for immunogenicity

Disease Control Rate (DCR) with SAR441000 in combination with cemiplimab. DCR is sum of Complete Response + Partial Response + Stable Disease

Duration of Response (DoR) with SAR441000 in combination with cemiplimab. DoR is time from initial response to the first documented tumor progression

Time from first drug administration to the first documented tumor progression or death from any cause, whichever comes first

Incidence of Adverse Events (AE)/ Serious AE (SAE) / Laboratory abnormalities considered to be adverse events

SAR441000 dose for administration in combination with cemiplimab selected for expansion phase based on MTD/MAD by the Bayesian model, the overall safety, activity and PK/PDy data

Assessment of overall response rate using standard imaging by RECIST 1.1 and iRECIST criteria

BioNTech RNA Pharmaceuticals GmbH

Sanofi

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antibodies

Antibodies, Monoclonal

Daratumumab

Immunoglobulins

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).

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).

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).

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).

Pharmaceutical form: solution for infusion

Route of administration: intravenous

isatuximab SAR650984

cemiplimab REGN2810

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.

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.

A Study of Isatuximab-based Therapy in Participants With Lymphoma

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

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.

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).

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.

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.

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.

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.

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.

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.

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.

Ceoi is the plasma concentration observed at the end of intravenous infusion of isatuximab.

Cmax was defined as the maximum plasma concentration observed after the first administration of drug.

Tmax was defined as the time to reach Cmax, after the intravenous 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.

Clast was defined as the last concentration of isatuximab observed above the lower limit of quantification.

Tlast was defined as the time of last concentration observed above the lower limit of quantification for 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.

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.

Ctrough was the plasma concentration of isatuximab observed just before treatment administration during repeated dosing.

Ceoi is the plasma concentration observed at the end of intravenous infusion of cemiplimab.

Cmax was defined as the maximum concentration observed after the first administration.

Tmax was defined as the time to reach Cmax after the intravenous 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.

Clast was defined as the last concentration of cemiplimab observed above the lower limit of quantification.

Tlast was defined as the time of last concentration observed above the lower limit of quantification for 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.

Ctrough was the serum concentration of cemiplimab observed just before treatment administration during repeated dosing.

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.

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.

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.

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.

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.

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.

Analysis was performed on all-treated population.

cHL, PD-1/PD-L1 inhibitor 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 then 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 A1: 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).

Cohort A2: cHL: Isatuximab + Cemiplimab

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 B: DLBCL: Isatuximab + Cemiplimab

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).

Cohort C: PTCL: Isatuximab + Cemiplimab

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Analysis was performed on all treated population which included all participants who signed the study informed consent and received at least 1 dose of the study treatment, either isatuximab or cemiplimab.

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.

Trial Transparency Team

Analysis was performed on DLT evaluable population which included all participants who received the planned doses of isatuximab and cemiplimab during Cycle 1 and completed the DLT observation period after the first administration of the study drug. Here, "0" in the "overall number of participants analyzed" signifies that no participants were evaluable for DLTs in the Cohort A1 arm.

Number of Participants With Dose Limiting Toxicities (DLTs)

TEAEs

TESAEs

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, 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).

Analysis was performed on all treated population which included all participants who signed the informed consent and received at least 1 dose of the study treatment, either isatuximab or cemiplimab.

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

Anemia: Grade 1

Anemia: Grade 2

Anemia: Grade 3

Anemia: Grade 4

White blood cell decreased: Grade 1

White blood cell decreased: Grade 2

White blood cell decreased: Grade 3

White blood cell decreased: Grade 4

Platelet count decreased: Grade 1

Platelet count decreased: Grade 2

Platelet count decreased: Grade 3

Platelet count decreased: Grade 4

Lymphocyte count decreased: Grade 1

Lymphocyte count decreased: Grade 2

Lymphocyte count decreased: Grade 3

Lymphocyte count decreased: Grade 4

Neutrophil count decreased: Grade 1

Neutrophil count decreased: Grade 2

Neutrophil count decreased: Grade 3

Neutrophil count decreased: Grade 4

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 Q2W 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).

Analysis was performed on all treated population.

Number of Participants With Laboratory Abnormalities: Hematological Parameters

Hyponatremia: Grade 1

Hyponatremia: Grade 2

Hyponatremia: Grade 3

Hyponatremia: Grade 4

Hypokalemia: Grade 1

Hypokalemia: Grade 2

Hypokalemia: Grade 3

Hypokalemia: Grade 4

Hyperkalemia: Grade 1

Hyperkalemia: Grade 2

Hyperkalemia: Grade 3

Hyperkalemia: Grade 4

Hypocalcemia: Grade 1

Hypocalcemia: Grade 2

Hypocalcemia: Grade 3

Hypocalcemia: Grade 4

Hypoalbuminemia: Grade 1

Hypoalbuminemia: Grade 2

Hypoalbuminemia: Grade 3

Hypoalbuminemia: Grade 4

Hypoglycemia: Grade 1

Hypoglycemia: Grade 2

Hypoglycemia: Grade 3

Hypoglycemia: Grade 4

Hyperglycemia: Grade 1

Hyperglycemia: Grade 2

Hyperglycemia: Grade 3

Hyperglycemia: Grade 4

Hypercalcemia: Grade 1

Hypercalcemia: Grade 2

Hypercalcemia: Grade 3

Hypercalcemia: Grade 4

cHL, PD-1/PD-L1 inhibitor naïve participants with 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 then 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).

DLBCL, anti PD-1/PD-L1 naïve participants with 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).

Analysis was performed on all treated population. Here "number analyzed" signifies the participants with available data for each specified parameter.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A First-in-Human Dose Escalation and Expansion Study to Evaluate Intratumoral Administration of SAR441000 as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors	NCT03871348	Metastatic Neop...	SAR441000 Cemiplimab REGN...	18 Years -	Sanofi
A Study of Isatuximab-based Therapy in Participants With Lymphoma	NCT03769181	Lymphoma	isatuximab SAR6... cemiplimab REGN...	12 Years -	Sanofi
A Study of Isatuximab-based Therapy in Participants With Lymphoma	NCT03769181	Lymphoma	isatuximab SAR6... cemiplimab REGN...	12 Years -	Sanofi
A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and Cemiplimab in Patients With Advanced Solid Tumors	NCT03192345	Malignant Solid...	SAR439459 Cemiplimab REGN...	18 Years -	Sanofi
Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients	NCT03194867	Plasma Cell Mye...	Isatuximab SAR6... Cemiplimab REGN...	18 Years -	Sanofi
Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients	NCT03194867	Plasma Cell Mye...	Isatuximab SAR6... Cemiplimab REGN...	18 Years -	Sanofi
A First-in-Human Dose Escalation and Expansion Study to Evaluate Intratumoral Administration of SAR441000 as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors	NCT03871348	Metastatic Neop...	SAR441000 Cemiplimab REGN...	18 Years -	Sanofi
Isatuximab in Combination With Cemiplimab in Relapsed/Refractory Multiple Myeloma (RRMM) Patients	NCT03194867	Plasma Cell Mye...	Isatuximab SAR6... Cemiplimab REGN...	18 Years -	Sanofi

Spots Global Cancer Trial Database for cemiplimab regn2810