Trial Outcomes & Findings for Safety, Preliminary Efficacy and PK of Isatuximab (SAR650984) Alone or in Combination With Atezolizumab in Patients With Advanced Malignancies (NCT NCT03637764)

Last Updated: 2023-07-10

Results Overview

DLTs: AEs occurring during 1st treatment cycle, unless due to disease progression/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 thrombocytopenia with clinically significant bleeding/ G4 thrombocytopenia. Non-hematological abnormalities: G \>=2 Aspartate transaminase (AST)/ Alanine transaminase (ALT) elevation simultaneous with G \>=2 total bilirubin elevation without initial findings of cholestasis or any other reason found, G4 non-hematologic AE, G3 to 4 cytokine release syndrome, 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 study committee deemed to be dose-limiting, regardless of grade, was also considered DLT.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

107 participants

Primary outcome timeframe

Cycle 1 (21 days)

Results posted on

2023-07-10

Participant Flow

Study was conducted at 26 active sites in 8 countries. A total of 107 participants were enrolled between 06 August 2018 and 21 July 2020 and received isatuximab in combination with atezolizumab. Study was planned to be conducted in 2 parts: Phase 1 (safety run-in) and Phase 2 (efficacy with a 2-stage design).

Study was stopped after performance of interim analysis for 4 cohorts (Cohort A \[HCC\], Cohort B \[SCCHN\], Cohort C \[EOC\] \& Cohort D-1 \[GBM\]) indicated that efficacy results observed in each cohort did not fulfill the preplanned interim analysis criteria allowing the study to move to Phase 2 Stage 2 in these 4 cohorts. Participant flow, Baseline, outcome measures and safety data were analyzed on combined Phase 1 and 2 populations.

Participant milestones

Participant milestones
Measure	Cohort A: Hepatocellular Carcinoma (HCC): Isatuximab + Atezolizumab Participants with hepatocellular carcinoma (HCC) received atezolizumab 1200 milligrams (mg), every 3 weeks (Q3W), intravenous (IV) infusion along with isatuximab 10 milligrams per kilogram (mg/kg), IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable adverse events (AE), participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 106 weeks).	Cohort B: Squamous Cell Carcinoma of the Head and Neck (SCCHN): Isatuximab + Atezolizumab Participants with squamous cell carcinoma of the head and neck (SCCHN) received atezolizumab 1200 milligrams,Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: Epithelial Ovarian Cancer (EOC): Isatuximab + Atezolizumab Participants with epithelial ovarian cancer (EOC) received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: Glioblastoma Multiforme (GBM): Isatuximab + Atezolizumab Participants with glioblastoma multiforme (GBM) received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Overall Study STARTED	27	29	18	33
Overall Study COMPLETED	1	3	0	0
Overall Study NOT COMPLETED	26	26	18	33

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Hepatocellular Carcinoma (HCC): Isatuximab + Atezolizumab Participants with hepatocellular carcinoma (HCC) received atezolizumab 1200 milligrams (mg), every 3 weeks (Q3W), intravenous (IV) infusion along with isatuximab 10 milligrams per kilogram (mg/kg), IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable adverse events (AE), participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 106 weeks).	Cohort B: Squamous Cell Carcinoma of the Head and Neck (SCCHN): Isatuximab + Atezolizumab Participants with squamous cell carcinoma of the head and neck (SCCHN) received atezolizumab 1200 milligrams,Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: Epithelial Ovarian Cancer (EOC): Isatuximab + Atezolizumab Participants with epithelial ovarian cancer (EOC) received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: Glioblastoma Multiforme (GBM): Isatuximab + Atezolizumab Participants with glioblastoma multiforme (GBM) received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Overall Study Adverse Event	2	0	0	1
Overall Study Progressive Disease	23	23	18	31
Overall Study Withdrawal by Subject	1	3	0	1

Baseline Characteristics

Safety, Preliminary Efficacy and PK of Isatuximab (SAR650984) Alone or in Combination With Atezolizumab in Patients With Advanced Malignancies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: HCC: Isatuximab + Atezolizumab n=27 Participants Participants with HCC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 106 weeks).	Cohort B: SCCHN: Isatuximab + Atezolizumab n=29 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=18 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab n=33 Participants Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure:54 weeks).	Total n=107 Participants Total of all reporting groups
Age, Continuous	62.8 years STANDARD_DEVIATION 11.8 • n=5 Participants	61.1 years STANDARD_DEVIATION 9.1 • n=7 Participants	56.3 years STANDARD_DEVIATION 10.6 • n=5 Participants	53.3 years STANDARD_DEVIATION 13.3 • n=4 Participants	58.3 years STANDARD_DEVIATION 12.0 • n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	3 Participants n=7 Participants	18 Participants n=5 Participants	10 Participants n=4 Participants	38 Participants n=21 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	26 Participants n=7 Participants	0 Participants n=5 Participants	23 Participants n=4 Participants	69 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	11 Participants n=5 Participants	9 Participants n=7 Participants	4 Participants n=5 Participants	0 Participants n=4 Participants	24 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	20 Participants n=7 Participants	13 Participants n=5 Participants	29 Participants n=4 Participants	77 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	6 Participants n=21 Participants

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

Population: Analysis was performed on DLT evaluable population that included participants who received planned doses of isatuximab and atezolizumab during Cycle 1 and who completed the DLT observation period.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=9 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Number of Participants With Dose Limiting Toxicities (DLTs)	0 Participants	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

Population: Analysis was performed on DLT evaluable population.

RP2D was the starting dose selected for Phase 2 part of the study. RP2D was the selected dose at which no more than 1 out of 6 participants (starting dose or dose level minus -1 \[DL-1\]) or 2 out of 12 participants (starting dose) experienced a DLT related to the investigational medicinal product. DLTs: Adverse Event (AE) occurring during 1st treatment cycle, unless due to disease progression/obviously unrelated cause included: hematological abnormalities: G4 N for 7/ more consecutive days, G3 to G4 N with fever, G3/G4 thrombocytopenia. Non-hematological abnormalities: G\>=2 AST/ALT elevation simultaneous with G \>=2 total bilirubin elevation without cholestasis or any other reason found, G4 non-hematologic AE, G3 to 4 cytokine release syndrome, G3 non-hematological AE lasting \>3 days, delay in initiation of Cycle 2 \>14 days due to treatment related laboratory abnormalities/AE.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=9 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Recommended Phase 2 Dose (RP2D)	10 milligrams per kilogram (mg/kg)	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 (21 days)

Population: Analysis was performed on DLT evaluable population.

MTD was defined as the highest dose level at which no more than 1 out of 6 participants (starting dose or DL-1) or 2 out of 12 participants (starting dose) experienced a DLT related to the investigational medicinal product. DLTs: AE occurring during 1st treatment cycle, unless due to disease progression/obviously unrelated cause included: hematological abnormalities: G4 N for 7 or more consecutive days, G3 to G4 N with fever, G3 or G4 thrombocytopenia. Non-hematological abnormalities: G\>=2 AST/ ALT elevation simultaneous with G \>=2 total bilirubin elevation without cholestasis or any other reason found, G4 non-hematologic AE, G3 to 4 cytokine release syndrome, G3 non-hematological AE lasting \>3 days, delay in initiation of Cycle 2 \>14 days due to treatment related laboratory abnormalities or AEs.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=9 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Maximum Tolerated Dose (MTD)	10 mg/kg	—	—	—

PRIMARY outcome

Timeframe: From randomization until disease progression, or death or study cut-off whichever occurred first (maximum duration of exposure: up to 108 weeks)

Population: Analysis was performed on all-treated population. Data for this outcome measure was not planned to be collected and analyzed for GBM Cohort as pre-specified in protocol.

OR was defined as the percentage of participants with complete response (CR) and partial response (PR) as best overall response, assessed per RECIST 1.1 criteria. Best overall response was derived per RECIST 1.1 criteria using disease assessments performed from the first dose of treatment throughout the study excluding any assessments performed after the cut-off date or following the initiation of a further anticancer treatment. CR was defined as the disappearance of all target lesions, pathological lymph nodes (target/non-target)- reduction in short axis \<10 mm; PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Disease progression was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum, sum with an absolute increase of diameter of at least 5 mm and appearance of \>1 new lesion.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=27 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab n=29 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=18 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Percentage of Participants With Overall Response (OR): For HCC/SCCHN/EOC Cohorts	7.4 percentage of participants Interval 1.3 to 21.5	13.8 percentage of participants Interval 4.9 to 28.8	5.6 percentage of participants Interval 0.3 to 23.8	—

PRIMARY outcome

Timeframe: From randomization until 6 months after the last participant's first treatment in the GBM Cohort D-1

Population: Analysis was performed on all-treated population. Data for this outcome measure was not planned to be collected and analyzed for Cohorts A: HCC, Cohort B: SCCHN and Cohort C: EOC as pre-specified in protocol.

PFS-6 was defined as the probability of participants alive without disease progression at 6 months as assessed by RANO criteria. Participants who didn't experience documented progression or death before analysis cut-off date or date of initiation of new anticancer treatment, PFS was censored at date of last valid disease assessment not showing progression performed prior to initiation of further anticancer treatment or analysis cut-off date, whichever was 1st. Per RANO criteria, progressive disease was defined as \>=25% increase size of T1- gadolinium enhancing disease, or increased T2/FLAIR signal, or presence of new lesion, or worsening clinical status. PFS-6 was evaluated by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=33 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Probability of Participants With Progression Free Survival at 6 Months (PFS-6): GBM Cohort	0.033 probability of participants Interval 0.002 to 0.145	—	—	—

PRIMARY outcome

Timeframe: From Baseline up to 30 days after last study treatment administration (maximum duration of exposure: 106 weeks for Cohort A, 108 weeks for Cohort B, 61 weeks for Cohort C and 54 weeks for Cohort D-1)

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) 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).

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=27 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab n=29 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=18 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab n=33 Participants Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (TESAEs) TEAE	26 Participants	29 Participants	18 Participants	33 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Treatment-emergent Adverse Events (TESAEs) TESAE	12 Participants	16 Participants	8 Participants	9 Participants

PRIMARY outcome

Population: Analysis was performed on all-treated population. Here, 'overall number of participants analyzed' signifies participants with available data for this outcome measure.

Hematological parameters assessed were anemia, white blood cell (WBC) decreased, platelet count decreased, lymphocyte count decreased, and neutrophil count decreased. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=26 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab n=29 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=18 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab n=32 Participants Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Number of Participants With Hematological Abnormalities Anemia: Grade 1	11 Participants	13 Participants	6 Participants	7 Participants
Number of Participants With Hematological Abnormalities Anemia: Grade 2	5 Participants	12 Participants	6 Participants	2 Participants
Number of Participants With Hematological Abnormalities Anemia: Grade 3	2 Participants	3 Participants	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Anemia: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities White blood cell decreased: Grade 1	9 Participants	5 Participants	4 Participants	12 Participants
Number of Participants With Hematological Abnormalities White blood cell decreased: Grade 2	2 Participants	1 Participants	2 Participants	3 Participants
Number of Participants With Hematological Abnormalities White blood cell decreased: Grade 3	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Hematological Abnormalities White blood cell decreased: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Platelet count decreased: Grade 1	11 Participants	5 Participants	5 Participants	10 Participants
Number of Participants With Hematological Abnormalities Platelet count decreased: Grade 2	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Platelet count decreased: Grade 3	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Platelet count decreased: Grade 4	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Lymphocyte count decreased: Grade 1	4 Participants	2 Participants	2 Participants	10 Participants
Number of Participants With Hematological Abnormalities Lymphocyte count decreased: Grade 2	8 Participants	14 Participants	7 Participants	12 Participants
Number of Participants With Hematological Abnormalities Lymphocyte count decreased: Grade 3	3 Participants	7 Participants	4 Participants	3 Participants
Number of Participants With Hematological Abnormalities Lymphocyte count decreased: Grade 4	0 Participants	4 Participants	0 Participants	1 Participants
Number of Participants With Hematological Abnormalities Neutrophil count decreased: Grade 1	3 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Hematological Abnormalities Neutrophil count decreased: Grade 2	0 Participants	0 Participants	3 Participants	2 Participants
Number of Participants With Hematological Abnormalities Neutrophil count decreased: Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Hematological Abnormalities Neutrophil count decreased: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Population: Analysis was performed on all-treated population. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.

Electrolyte parameters assessed were hyponatremia, hypernatremia, hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypoalbuminemia, hypoglycemia and hyperglycemia. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=26 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab n=29 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=18 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab n=32 Participants Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Number of Participants With Abnormal Electrolyte Parameters Hypoalbuminemia: Grade 1	9 Participants	7 Participants	7 Participants	2 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypoalbuminemia: Grade 2	1 Participants	3 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyponatremia: Grade 1	9 Participants	12 Participants	8 Participants	4 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyponatremia: Grade 2	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyponatremia: Grade 3	1 Participants	4 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyponatremia: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypokalemia: Grade 1	2 Participants	5 Participants	4 Participants	4 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypokalemia: Grade 2	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypokalemia: Grade 3	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypokalemia: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyperkalemia: Grade 1	5 Participants	6 Participants	2 Participants	2 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyperkalemia: Grade 2	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyperkalemia: Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyperkalemia: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypocalcemia: Grade 1	9 Participants	7 Participants	2 Participants	9 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypocalcemia: Grade 2	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypocalcemia: Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypocalcemia: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypercalcemia: Grade 1	1 Participants	5 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypercalcemia: Grade 2	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypercalcemia: Grade 3	1 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypercalcemia: Grade 4	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypoalbuminemia: Grade 3	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypoalbuminemia: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypoglycemia: Grade 1	1 Participants	3 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypoglycemia: Grade 2	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypoglycemia: Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypoglycemia: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyperglycemia: Grade 1	10 Participants	7 Participants	2 Participants	8 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyperglycemia: Grade 2	5 Participants	6 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyperglycemia: Grade 3	1 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Electrolyte Parameters Hyperglycemia: Grade 4	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypernatremia: Grade 1	0 Participants	4 Participants	0 Participants	5 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypernatremia: Grade 2	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypernatremia: Grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrolyte Parameters Hypernatremia: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Population: Analysis was performed on all-treated population. Here 'overall number of participants analyzed' signifies participants with available data 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. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=26 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab n=29 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=18 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab n=32 Participants Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Number of Participants With Renal Function Abnormalities CrCl: >=60 - <90 mL/min/1.73m^2	8 Participants	13 Participants	10 Participants	16 Participants
Number of Participants With Renal Function Abnormalities CrCl: >=30 - <60mL/min/1.73m^2	5 Participants	4 Participants	5 Participants	1 Participants
Number of Participants With Renal Function Abnormalities CrCl: >=15 - <30 mL/min/1.73m^2	3 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities CrCl: <15 mL/min/1.73m^2	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities Creatinine increased: Grade 1	22 Participants	19 Participants	13 Participants	24 Participants
Number of Participants With Renal Function Abnormalities Creatinine increased: Grade 2	2 Participants	2 Participants	2 Participants	0 Participants
Number of Participants With Renal Function Abnormalities Creatinine increased: Grade 3	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities Creatinine increased: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities Hyperuricemia: Grade 1	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities Hyperuricemia: Grade 2	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Renal Function Abnormalities Hyperuricemia: Grade 3	5 Participants	7 Participants	5 Participants	3 Participants
Number of Participants With Renal Function Abnormalities Hyperuricemia: Grade 4	1 Participants	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Population: Analysis was performed on all-treated population. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.

Abnormal liver function parameters assessed were AST increased, ALT increased, alkaline phosphatase (ALP) increased, blood bilirubin (BB) increased. Parameters were assessed as per the National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Potentially Life Threatening. Grade refers to the severity of the AEs.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=26 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab n=29 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=18 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab n=32 Participants Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Number of Participants With Liver Abnormalities AST increased: Grade 1	14 Participants	5 Participants	6 Participants	3 Participants
Number of Participants With Liver Abnormalities AST increased: Grade 2	5 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Liver Abnormalities AST increased: Grade 3	3 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Liver Abnormalities AST increased: Grade 4	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Liver Abnormalities ALT increased: Grade 1	11 Participants	8 Participants	6 Participants	11 Participants
Number of Participants With Liver Abnormalities ALT increased: Grade 2	4 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Liver Abnormalities ALT increased: Grade 3	2 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Liver Abnormalities ALT increased: Grade 4	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Liver Abnormalities ALP increased: Grade 1	12 Participants	13 Participants	7 Participants	0 Participants
Number of Participants With Liver Abnormalities ALP increased: Grade 2	8 Participants	2 Participants	3 Participants	0 Participants
Number of Participants With Liver Abnormalities ALP increased: Grade 3	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Liver Abnormalities ALP increased: Grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Liver Abnormalities BB increased: Grade 1	6 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Liver Abnormalities BB increased: Grade 2	2 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Liver Abnormalities BB increased: Grade 3	3 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Liver Abnormalities BB increased: Grade 4	1 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline up to 30 days after last study treatment administration (maximum duration of exposure:106 weeks for Cohort A, 108 weeks for Cohort B, 61 weeks for Cohort C and 54 weeks for Cohort D-1)

Population: Analysis was performed on ADA evaluable population which included all participants who received at least 1 dose of study treatment with at least 1 non-missing ADA result after the drug administration. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.

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 (including participants without pretreatment samples).

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=25 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab n=24 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=17 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab n=30 Participants Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab Treatment-induced ADA	2 count of participants	0 count of participants	1 count of participants	1 count of participants
Number of Participants With Anti-drug Antibodies (ADA) Response Against Isatuximab Treatment boosted ADA	0 count of participants	0 count of participants	0 count of participants	0 count of participants

SECONDARY outcome

Population: Analysis was performed on ADA evaluable population. Here 'overall number of participants analyzed' signifies participants with available data for this outcome measure.

Outcome measures

Outcome measures
Measure	Isatuximab + Atezolizumab n=25 Participants Participants with HCC, SCCHN, EOC, or GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first.	Cohort B: SCCHN: Isatuximab + Atezolizumab n=25 Participants Participants with SCCHN received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 108 weeks).	Cohort C: EOC: Isatuximab + Atezolizumab n=17 Participants Participants with EOC received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 61 weeks).	Cohort D-1: GBM: Isatuximab + Atezolizumab n=30 Participants Participants with GBM received atezolizumab 1200 mg, Q3W, IV infusion along with isatuximab 10 mg/kg, IV infusion, once weekly for 3 weeks (i.e., on Day 1, Day 8 and Day 15 of Cycle 1) and then Q3W (i.e., on Day 1 of each 21- day treatment cycle) until disease progression, unacceptable AE, participant's decision to stop the treatment, or death or study cut-off whichever occurred first (maximum duration of exposure: 54 weeks).
Number of Participants With Anti-drug Antibodies (ADA) Response Against Atezolizumab Treatment-induced ADA	2 count of participants	2 count of participants	1 count of participants	0 count of participants
Number of Participants With Anti-drug Antibodies (ADA) Response Against Atezolizumab Treatment boosted ADA	0 count of participants	0 count of participants	0 count of participants	0 count of participants

SECONDARY outcome

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

Population: Analysis was performed on PK population which included all participants who received at least 1 dose of the study treatment with at least one reportable concentration after the study drug administration.

Cmax was defined as the maximum concentration observed after the first administration calculated using the noncompartmental analysis after the intravenous infusion of isatuximab.