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

Sanofi

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Neoplasm

Treatments: Drug: Isatuximab SAR650984; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03637764

2018-000390-67 (EudraCT Number)

U1111-1202-0839 (Other Identifier)

ACT15377

Details and patient eligibility

About

Primary Objectives:

• Phase 1: To characterize the safety and tolerability of isatuximab in combination with atezolizumab in participants with unresectable hepatocellular carcinoma (HCC), platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN), platinum-resistant/refractory epithelial ovarian cancer (EOC), or recurrent glioblastoma multiforme (GBM), and to determine the recommended Phase 2 dose (RP2D).
• Phase 2: To assess response rate (RR) of isatuximab in combination with atezolizumab in participants with HCC or SCCHN or EOC.
• Phase 2: To assess the progression free survival rate at 6 months (PFS-6) of isatuximab in combination with atezolizumab, or as a single agent in participants with GBM.

Secondary Objectives:

• To evaluate the safety profile of isatuximab monotherapy (GBM only), or in combination with atezolizumab in Phase 2.
• To evaluate the immunogenicity of isatuximab and atezolizumab.
• To characterize the pharmacokinetic (PK) profile of isatuximab single agent (GBM only) and atezolizumab in combination with isatuximab.
• To assess the overall efficacy of isatuximab in combination with atezolizumab, or single agent (GBM only).

Full description

The total study duration per participant was up to 28 months including up to 28 days screening period, up to 24 months treatment period, and a 3 month safety follow up period.

Enrollment: 107 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must have a known diagnosis of either unresectable HCC, platinum-refractory recurrent/metastatic SCCHN, platinum-resistant/refractory EOC with evidence of measurable disease or recurrent GBM.
• Greater than or equal to (>=)18 years of age.
• For participants with HCC: Documentation of progressive disease (PD) during or after treatment with either sorafenib or lenvatinib, or intolerance to the therapy.
• For participants with SCCHN: Received and failed up to 2 lines of prior systemic anti-cancer therapy with documentation of tumor recurrence or PD within 6 months of last platinum-based therapy in primary, recurrent, or metastatic setting.
• For participants with EOC: Received up to 3 lines of prior platinum-containing therapy when the disease was platinum-sensitive, and the participants should not have received any systemic therapy for platinum-resistant/refractory disease. Specific to France only: Documentation of PD on or after 1 line of anti-cancer therapy for platinum resistant/refractory disease (unless participants are ineligible or intolerant to standard of care for platinum-resistant/refractory disease).
• For participants with GBM: Documentation of PD or first recurrence during or after temozolomide maintenance therapy for newly diagnosed GBM treated with 1st line radiotherapy plus concurrent temozolomide.

Exclusion criteria

• Prior exposure to agent that blocks CD38 or participation in clinical studies with isatuximab.
• For participants with HCC, SCCHN, EOC or GBM prior exposure to any agent (approved or investigational) that blocks the PD-1/PD-L1 pathway.
• Evidence of other immune related disease /conditions.
• History of non-infectious pneumonitis requiring steroids or current pneumonitis; history of the thoracic radiation.
• Received a live-virus vaccination within 28 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.
• Prior solid organ or bone marrow transplantation.
• Eastern Cooperative Oncology Group performance status >=2 for participants with HCC, SCCHN or EOC or Karnofsky performance score less than or equal to (<=) 70 for participants with GBM.
• Poor bone marrow reserve.
• Poor organ function.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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107 participants in 4 patient groups

Cohort A: HCC: Isatuximab + Atezolizumab

Experimental group

Description:

Participants with hepatocellular carcinoma (HCC) received atezolizumab 1200 milligrams, 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).

Treatment:

Drug: Isatuximab SAR650984

Drug: Atezolizumab

Cohort B: SCCHN: Isatuximab + Atezolizumab

Experimental group

Description:

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).

Treatment:

Drug: Isatuximab SAR650984

Drug: Atezolizumab

Cohort C: EOC: Isatuximab + Atezolizumab

Experimental group

Description:

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).

Treatment:

Drug: Isatuximab SAR650984

Drug: Atezolizumab

Cohort D-1: GBM: Isatuximab + Atezolizumab

Experimental group

Description:

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).

Treatment:

Drug: Isatuximab SAR650984

Drug: Atezolizumab