Trial Outcomes & Findings for Isatuximab in Combination With REGN2810 (Cemiplimab) in Patients With Advanced Malignancies (NCT NCT03367819)

Last Updated: 2022-05-16

Results Overview

DLTs: adverse events occurring during 1st treatment cycle, unless due to disease progression/to cause obviously unrelated to investigational medicinal product (IMP) which included:hematological abnormalities: Grade(G) 4 neutropenia(N) for 7/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. Non-hematological abnormalities: G4 non-hematologic AE, G\>=2 uveitis, G3 non-hematological AE lasting greater than (\>)3 days (except G3 fatigue, allergic reaction/hypersensitivity attributed to isatuximab or REGN2810 and G3 or G4 clinically non-significant laboratory abnormality), delay in initiation of Cycle 2 \>14 days due to treatment related laboratory abnormalities/AE. Any other toxicity that Investigator and Sponsor deemed to be dose-limiting, regardless of grade, was also considered as DLT.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

44 participants

Primary outcome timeframe

Cycle 1 (21 days)

Results posted on

2022-05-16

Participant Flow

Study was conducted at 16 active sites in 5 countries. A total of 44 participants were enrolled between 04 January 2018 and 18 January 2019 and received isatuximab in combination with REGN2810.

The study was planned to be conducted in 3 parts: Phase 1 part (safety run-in), Phase 2 part (efficacy) and Cross-over part (a subpart of Cohort A-2). Since the enrolled participants (24 for metastatic, castration-resistant prostate cancer \[mCRPC\] Cohort A-1 and 20 participants for non-small cell lung cancer \[NSCLC\] Cohort B) did not achieve the pre-defined efficacy criteria, the study was stopped per-protocol and thus, few planned outcome measures were not analyzed.

Participant milestones

Participant milestones
Measure	mCRPC: Isatuximab + REGN2810 Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Overall Study STARTED	24	20
Overall Study COMPLETED	0	1
Overall Study NOT COMPLETED	24	19

Reasons for withdrawal

Reasons for withdrawal
Measure	mCRPC: Isatuximab + REGN2810 Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Overall Study Adverse Event	4	4
Overall Study Progressive Disease	15	13
Overall Study Withdrawal by Subject	1	0
Overall Study Other	4	2

Baseline Characteristics

Isatuximab in Combination With REGN2810 (Cemiplimab) in Patients With Advanced Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	mCRPC: Isatuximab + REGN2810 n=24 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	Total Title n=44 Participants
Age, Continuous	70.7 years STANDARD_DEVIATION 6.5 • n=5 Participants	65.4 years STANDARD_DEVIATION 5.8 • n=7 Participants	68.3 years STANDARD_DEVIATION 6.7 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	14 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	10 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

Population: Analysis was performed on DLT evaluable population which included participants who received the planned doses of isatuximab and REGN2810 during Cycle 1, and who completed the DLT observation period after the first IMP administration, unless they discontinued the study treatment(s) due to DLT.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=5 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=1 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

Population: Analysis was performed on all-treated population.

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) was 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). TEAEs included both SAEs and non-SAEs.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=24 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TEAEs	24 Participants	20 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TESAEs	11 Participants	14 Participants

PRIMARY outcome

Timeframe: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

Population: Analysis was performed on all-treated population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Hematological parameters assessed were anemia, white blood cell (WBC) decreased, platelet count decreased, lymphocyte count decreased and neutrophil count decreased. Abnormality criteria was based on National Cancer Institute Common Terminology Criteria for Adverse Event version 4.03 (NCI-CTCAE v 4.03), where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Only those categories in which at least 1 participant had data were reported.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=23 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Number of Participants With Laboratory Abnormalities: Hematological Parameters Anemia: Grade 1	10 Participants	9 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Anemia: Grade 2	9 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Anemia: Grade 3	4 Participants	3 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters WBC decreased: Grade 1	8 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters WBC decreased: Grade 2	5 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Platelet count decreased: Grade 1	5 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Platelet count decreased: Grade 2	2 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Platelet count decreased: Grade 3	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Lymphocyte count decreased: Grade 1	4 Participants	7 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Lymphocyte count decreased: Grade 2	8 Participants	4 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Lymphocyte count decreased: Grade 3	5 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Lymphocyte count decreased: Grade 4	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Neutrophil count decreased: Grade 1	3 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Hematological Parameters Neutrophil count decreased: Grade 2	2 Participants	0 Participants

PRIMARY outcome

Timeframe: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

Population: Analysis was performed on all-treated population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Abnormal electrolytes parameters assessed were hyponatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypoalbuminemia and hyperglycemia. Abnormality criteria was based on NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Only those categories in which at least 1 participant had data were reported.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=23 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Number of Participants With Laboratory Abnormalities: Electrolytes Hyponatremia: Grade 1	8 Participants	8 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypokalemia: Grade 1	3 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hyperkalemia: Grade 1	3 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypocalcemia: Grade 1	6 Participants	3 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypocalcemia: Grade 2	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypercalcemia: Grade 1	1 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypercalcemia: Grade 2	0 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypoalbuminemia: Grade 1	6 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypoalbuminemia: Grade 2	1 Participants	3 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypoalbuminemia: Grade 3	0 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hyperglycemia: Grade 1	11 Participants	3 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hyperglycemia: Grade 2	5 Participants	5 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hyperglycemia: Grade 3	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypoglycemia: Grade 1	0 Participants	1 Participants
Number of Participants With Laboratory Abnormalities: Electrolytes Hypoglycemia: Grade 2	0 Participants	1 Participants

PRIMARY outcome

Timeframe: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

Population: Analysis was performed on all-treated population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Abnormal renal parameters assessed were creatinine clearance (CrCl), creatinine increased and hyperuricemia. Creatinine clearance was assessed in categories: \>=60 - less than (\<) 90 milliliters per minute per 1.73 square meter (mL/min/1.73m\^2), \>=30 - \<60 mL/min/1.73m\^2, \>=15 - \<30 mL/min/1.73m\^2 and \<15 mL/min/1.73m\^2. Creatinine increased and hyperuricemia abnormality criteria was based on NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. For all these 3 parameters, only those categories in which at least 1 participant had data were reported.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=23 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Number of Participants With Laboratory Abnormalities: Renal Parameters CrCl: >=30 - <60 mL/min/1.73m^2	11 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Renal Parameters Creatinine increased: Grade 1	18 Participants	15 Participants
Number of Participants With Laboratory Abnormalities: Renal Parameters Hyperuricemia: Grade 3	2 Participants	3 Participants
Number of Participants With Laboratory Abnormalities: Renal Parameters CrCl: >=60 - <90 mL/min/1.73m^2	6 Participants	13 Participants
Number of Participants With Laboratory Abnormalities: Renal Parameters Hyperuricemia: Grade 4	1 Participants	0 Participants

PRIMARY outcome

Timeframe: From Baseline up to 30 days after the last dose of study treatments (maximum duration: up to 2 years)

Population: Analysis was performed on all-treated population. Here, overall number of participants analyzed = participants evaluable for this outcome measure.

Abnormal liver function parameters assessed were aspartate aminotransferase (AST) increased, alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, blood bilirubin (BB) increased. Abnormality criteria was based on NCI-CTCAE v 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Only those categories in which at least 1 participant had data were reported.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=23 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Number of Participants With Laboratory Abnormalities: Liver Function Parameters AST increased: Grade 1	6 Participants	2 Participants
Number of Participants With Laboratory Abnormalities: Liver Function Parameters AST increased: Grade 2	1 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Liver Function Parameters ALT increased: Grade 1	2 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Liver Function Parameters ALP increased: Grade 1	3 Participants	9 Participants
Number of Participants With Laboratory Abnormalities: Liver Function Parameters ALP increased: Grade 2	4 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Liver Function Parameters ALP increased: Grade 3	6 Participants	0 Participants
Number of Participants With Laboratory Abnormalities: Liver Function Parameters BB increased: Grade 1	2 Participants	1 Participants

PRIMARY outcome

Timeframe: From the date of randomization to the date of first documentation of progression or death due to any cause, whichever occurred first (maximum duration: up to 2 years)

Population: Analysis was performed on all-treated population.

For participants with mCRPC, response was defined as achieving complete response (CR) or partial response (PR) as best overall response (BOR) for soft tissue assessed and confirmed by the Investigators and/or a prostate-specific antigen (PSA) decline of \>=50 percent (%) from Baseline that was subsequently confirmed per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. For participants with NSCLC, ORR was defined as the percentage of participants with CR or PR as BOR according to RECIST 1.1. criteria. Per RECIST 1.1. criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to \<10 millimeters (mm) and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=24 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Overall Response Rate (ORR): Percentage of Participants With Overall Response	4.2 percentage of participants Interval 0.2 to 18.3	0 percentage of participants Interval 0.0 to 13.9

SECONDARY outcome

Timeframe: From Baseline up to 2 years

Population: Analyzed on ADA population: all participants who signed the study IC and received at least 1 dose (even incomplete) of the study treatments, either isatuximab or REGN2810 and had at least 1 ADA non-missing results after the first dose of study treatment. Here, 'overall number of participants analyzed'= participants evaluable for this outcome measure. For this outcome measure, combined ADA analysis was planned and performed for participants with mCRPC and NSCLC.

ADA response 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 (including participants without pretreatment samples).

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=39 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab, Post Treatment	0 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to 2 years

Population: Analysis was performed on ADA population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure. For this outcome measure, combined ADA analysis was planned and performed for participants with mCRPC and NSCLC.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=39 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Number of Participants With Anti-drug Antibodies (ADA) Response Against REGN2810, Post Treatment	1 Participants	—

SECONDARY outcome

Timeframe: At start of infusion (SOI), before actual end of infusion (EOI), EOI+4 hours, 72 hours and 168 hours post-dose on Day 1 of Cycle 1

Population: Analyzed on PK population which included all participants who signed the study IC and received at least 1 dose (even incomplete) of the study treatments, either isatuximab or REGN2810 and had at least 1 drug concentration after the first dose of study treatment. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Cmax was defined as the maximum observed plasma concentration. Cmax analysis was done separately for isatuximab for participants with mCRPC and NSCLC.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=17 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=16 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) After the First Infusion of Isatuximab	291 micrograms per milliliter Standard Deviation 67.9	280 micrograms per milliliter Standard Deviation 54.5

SECONDARY outcome

Timeframe: At SOI, before actual EOI, EOI+4 hours, 72 hours, 168 hours, and 336 hours post-dose on Day 1 of Cycle 1

Population: Analysis was performed on PK population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Cmax was defined as the maximum observed plasma concentration. Cmax analysis was done separately for REGN2810 for participants with mCRPC and NSCLC.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=19 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=17 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) After the First Infusion of REGN2810	102 milligrams per liter Standard Deviation 26.1	116 milligrams per liter Standard Deviation 21.4

SECONDARY outcome

Timeframe: At SOI, before actual EOI, EOI+4 hours, 72 hours and 168 hours post-dose on Day 1 of Cycle 1

Population: Analysis was performed on PK population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

AUC0-168 hr was defined as the area under the plasma concentration-time curve from time zero to 168h and was calculated using the trapezoidal method over the dosing interval (i.e., 7 days) for isatuximab alone.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=16 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=14 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 168 Hours (AUC0-168 hr) After the First Administration of Isatuximab	28400 micrograms*hour per milliliter Standard Deviation 6610	24500 micrograms*hour per milliliter Standard Deviation 5510

SECONDARY outcome

Timeframe: At SOI, before actual EOI, EOI+4 hours, 72 hours, 168 hours, 336 hours and 504 hours post-dose on Day 1 of Cycle 1

Population: Analysis was performed on PK population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

AUC0-504 hr was defined as the area under the plasma concentration-time curve from time zero to 504h and was calculated using the trapezoidal method over the dosing interval (i.e., 21 days) for REGN2810 alone.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=19 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=7 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504 hr) After the First Administration of REGN2810	903 milligrams*day per liter Standard Deviation 257	1020 milligrams*day per liter Standard Deviation 229

SECONDARY outcome

Timeframe: Up to 2 years

Population: Analysis was performed on all-treated population.

Tumor burden change was defined as the best percent-change from Baseline in a sum of the diameters (longest for non-nodal lesion, short axis for nodal lesions) for all target lesions.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=24 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Best Percent-change From Baseline in Tumor Burden	12.9 percent change Standard Deviation 47.6	0.7 percent change Standard Deviation 10.1

SECONDARY outcome

Timeframe: From the date of first response until disease progression or death, whichever occurred first (maximum duration: up to 2 years)

Population: Analysis was performed on subset of participants who had response. Here, '0' in 'overall number of participants analyzed represents that DOR could only be analyzed in participants who achieved a response. As no participant in the NSCLC cohort achieved any response, no DOR is available.

DOR: defined as time (in months) from date of first response (PR or CR in radiographic objective response, or PSA decline \>=50% for participants with mCRPC) that was subsequently confirmed to the date of first disease progression (PD) or death, whichever occurred first. PD included radiographic disease progression or unequivocal clinical progression. RECIST 1.1 criteria was used to assess radiographic PD in participants with NSCLC and PCWG3 criteria for participants with mCRPC. Per RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target/non-target) must had reduction in short axis to \<10 mm and PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (Baseline sum if that was smallest), sum with an absolute increase of at least 5 mm and appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=1 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Duration of Response (DOR)	4.17 months	—

SECONDARY outcome

Timeframe: From the date of the first study treatment administration to the date of first documented disease progression or death of any cause, whichever occurred first (maximum duration: up to 2 years)

Population: Analysis was performed on all-treated population.

For mCRPC participants, PFS was defined as the time (in months) from first study treatment administration to the date of first documented disease progression or the date of death from any cause, whichever occurred first. Disease progression included radiographic disease progression (per PCWG3 criteria) or unequivocal clinical progression. For NSCLC participants, PFS was defined as the time from first study treatment administration to the date of first documented radiographic progression (PD) (per RECIST 1.1) or the date of death from any cause, whichever occurred first. Per RECIST 1.1 criteria, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the Baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions was also considered as progression. Analysis was performed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=24 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 n=20 Participants Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Progression-free Survival (PFS)	2.30 months Interval 1.906 to 4.271	4.01 months Interval 1.938 to 4.074

SECONDARY outcome

Timeframe: From the date of first response to the date of first documented disease progression or death (due to any cause) (maximum duration: up to 2 years)

Population: Analysis was performed on all-treated population. Here, '0' in 'overall number of participants analyzed represents that data for this outcome measure was not analyzed for NSCLC arm because there was insufficient data to perform the DC analysis.

Disease control: defined as percentage of participants with confirmed CR/PR/stable disease (SD), as assessed by Investigator PCWG3 modified RECIST 1.1 criteria relative to total number of participants in analysis population. Per PCWG3 modified RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target/non-target) must had reduction in short axis to \<10 mm, PR: at least a 30% decrease in sum of diameters of target lesions, taking as reference Baseline sum diameters and SD: neither sufficient shrinkage from the Baseline to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum diameters while on study. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study, sum with an absolute increase of diameter of at least 5 mm and appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	mCRPC: Isatuximab + REGN2810 n=24 Participants Participants with mCRPC received intravenous (IV) infusion of isatuximab 10 milligrams per kilogram (mg/kg) once weekly (QW) for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).	NSCLC: Isatuximab + REGN2810 Participants with NSCLC received IV infusion of isatuximab 10 mg/kg QW for 3 weeks (i.e., on Days 1, 8 and 15) of Cycle 1 and then on Day 1 of Cycle 2 and subsequent cycles (each cycle of 21 days), along with REGN2810 350 mg IV infusion on Day 1 of each 21-day treatment Cycle (maximum duration: up to 2 years).
Percentage of Participants With Disease Control (DC) >=6 Months	20.8 percentage of participants Interval 8.6 to 38.9	—

Adverse Events

mCRPC: Isatuximab + REGN2810

Serious events: 11 serious events

Other events: 24 other events

Deaths: 2 deaths

NSCLC: Isatuximab + REGN2810

Serious events: 14 serious events

Other events: 19 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER