A Phase 1/2 Open-label, Multi-center, Safety, Preliminary Efficacy and Pharmacokinetic (PK) Study of Isatuximab (SAR650984) in Combination With Atezolizumab or Isatuximab Alone in Patients With Advanced Malignancies

Number of Participants With Abnormal Electrolyte Parameters

时间窗: 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)

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.

Maximum Tolerated Dose (MTD)

时间窗: Cycle 1 (21 days)

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.

Number of Participants With Dose Limiting Toxicities (DLTs)

时间窗: Cycle 1 (21 days)

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.

Percentage of Participants With Overall Response (OR): For HCC/SCCHN/EOC Cohorts

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

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.

Recommended Phase 2 Dose (RP2D)

时间窗: Cycle 1 (21 days)

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.

Probability of Participants With Progression Free Survival at 6 Months (PFS-6): GBM Cohort

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

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.

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

时间窗: 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)

An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the TEAE period (defined as the time from the first dose of study treatment up to 30 days after the last dose of study treatment).

Number of Participants With Hematological Abnormalities

时间窗: 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)

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.

Number of Participants With Renal Function Abnormalities

时间窗: 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)

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.

Number of Participants With Liver Abnormalities

时间窗: 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)

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.