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

NCT ID: NCT03637764

Last Updated: 2023-07-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-06
• Study Completion Date: 2022-05-11

Brief Summary

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).

Detailed 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.

Conditions

Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: HCC: Isatuximab + Atezolizumab

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).

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Atezolizumab

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Cohort B: 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).

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Atezolizumab

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Cohort C: 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).

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Atezolizumab

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Cohort D-1: 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).

Group Type: EXPERIMENTAL

Isatuximab SAR650984

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Atezolizumab

Intervention Type: DRUG

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Interventions

Isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Intervention Type: DRUG

Atezolizumab

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Intervention Type: DRUG

Other Intervention Names

Sarclisa; Tecentriq®

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number :8400004

Santa Monica, California, United States

Investigational Site Number :8400007

Boston, Massachusetts, United States

Investigational Site Number :8400002

Houston, Texas, United States

Investigational Site Number :0560001

Brussels, , Belgium

Investigational Site Number :0560002

Ghent, , Belgium

Investigational Site Number :1240001

Toronto, Ontario, Canada

Investigational Site Number :2030001

Brno, , Czechia

Investigational Site Number :2030003

Olomouc, , Czechia

Investigational Site Number :2030002

Prague, , Czechia

Investigational Site Number :3800007

Meldola, Forlì-Cesena, Italy

Investigational Site Number :3800003

Rozzano, Milano, Italy

Investigational Site Number :3800009

Milan, , Italy

Investigational Site Number :3800004

Padua, , Italy

Investigational Site Number :5280001

Rotterdam, , Netherlands

Investigational Site Number :7240001

Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number :7240006

Hospitalet de Llobregat, Castille and León, Spain

Investigational Site Number :7240004

Madrid, Madrid, Comunidad de, Spain

Investigational Site Number :7240003

Madrid / Madrid, Madrid, Comunidad de, Spain

Investigational Site Number :7240008

Pamplona, Navarre, Spain

Investigational Site Number :7240007

Madrid, , Spain

Investigational Site Number :1580005

Kaohsiung City, , Taiwan

Investigational Site Number :1580002

Tainan City, , Taiwan

Investigational Site Number :1580003

Taipei, , Taiwan

Investigational Site Number :1580006

Taipei, , Taiwan

Investigational Site Number :1580004

Taipei, , Taiwan

Investigational Site Number :1580001

Taipei, , Taiwan

Countries

United States; Belgium; Canada; Czechia; Italy; Netherlands; Spain; Taiwan

References

Simonelli M, Garralda E, Eskens F, Gil-Martin M, Yen CJ, Obermannova R, Chao Y, Lonardi S, Melichar B, Moreno V, Yu ML, Bongiovanni A, Calvo E, Rottey S, Machiels JP, Gonzalez-Martin A, Paz-Ares L, Chang CL, Mason W, Lin CC, Reardon DA, Vieito M, Santoro A, Meng R, Abbadessa G, Menas F, Lee H, Liu Q, Combeau C, Ternes N, Ziti-Ljajic S, Massard C. Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study. ESMO Open. 2022 Oct;7(5):100562. doi: 10.1016/j.esmoop.2022.100562. Epub 2022 Aug 18.

Reference Type: BACKGROUND

PMID: 35987165 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-000390-67

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1202-0839

Identifier Type: OTHER

Identifier Source: secondary_id

ACT15377

Identifier Type: -

Identifier Source: org_study_id