Clinical Trials /

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

NCT03637764

Description:

Primary Objectives: - Phase1: 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). - Phase2: To assess response rate (RR) of isatuximab in combination with atezolizumab in participants with HCC or SCCHN or EOC. - Phase2: 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).

Related Conditions:
  • Glioblastoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ACT15377
  • SECONDARY ID: 2018-000390-67
  • SECONDARY ID: U1111-1202-0839
  • NCT ID: NCT03637764

Conditions

  • Neoplasm

Interventions

DrugSynonymsArms
Isatuximab SAR650984Phase2-Cohort A: HCC
AtezolizumabTecentriq®Phase2-Cohort A: HCC

Purpose

Primary Objectives: - Phase1: 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). - Phase2: To assess response rate (RR) of isatuximab in combination with atezolizumab in participants with HCC or SCCHN or EOC. - Phase2: 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 patient is up to 28 months including an up to 28 days screening
      period, an up to 24 months treatment period, and a 3 months safety follow up period.
    

Trial Arms

NameTypeDescriptionInterventions
Phase1ExperimentalIsatuximab and atezolizumab combination in patients 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): Isatuximab dose 1 depending on DLT observed and atezolizumab predefined dose Q3W
  • Isatuximab SAR650984
  • Atezolizumab
Phase2-Cohort A: HCCExperimentalIsatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
  • Isatuximab SAR650984
  • Atezolizumab
Phase2-Cohort B: SCCHNExperimentalIsatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
  • Isatuximab SAR650984
  • Atezolizumab
Phase2-Cohort C: EOCExperimentalIsatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
  • Isatuximab SAR650984
  • Atezolizumab
Phase2-Cohort D-1:GBMExperimentalIsatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
  • Isatuximab SAR650984
  • Atezolizumab
Phase2-Cohort D-2: GBM, isatuximab monotherapyExperimentalIsatuximab dose 2
  • Isatuximab SAR650984
Phase2-Cohort EExperimentalIsatuximab and atezolizumab combination: Isatuximab dose 3 and atezolizumab predefined dose Q3W in participants with one tumor type (HCC, SCCHN, EOC, or GBM), or isatuximab monotherapy (GBM only) dose 3
  • Isatuximab SAR650984
  • Atezolizumab

Eligibility Criteria

        Inclusion criteria :

          -  Patients must have a known diagnosis of either unresectable hepatocellular carcinoma
             (HCC), platinum-refractory recurrent/metastatic squamous cell carcinoma of the head
             and neck (SCCHN), platinum-resistant/refractory epithelial ovarian cancer (EOC) with
             evidence of measurable disease or recurrent glioblastoma multiforme (GBM).

          -  ≥18 years of age.

          -  For patients with HCC: Documentation of progressive disease (PD) during or after
             treatment with either sorafenib or lenvatinib, or intolerance to the therapy.

          -  For patients 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 patients with EOC: Received up to 3 lines of prior platinum-containing therapy
             when the disease was platinum-sensitive, and the patients 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 patients are ineligible or intolerant to standard
             of care for platinum-resistant/refractory disease).

          -  For patients 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 patients 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.

          -  Has 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 (PS) ≥2 for patients with HCC,
             SCCHN or EOC or Karnofsky performance score ≤ 70 for patients with GBM.

          -  Poor bone marrow reserve.

          -  Poor organ function.

        The above information is not intended to contain all considerations relevant to a patient's
        potential participation in a clinical trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicities (DLTs)
Time Frame:Up to 3 weeks after first study treatment administration
Safety Issue:
Description:DLTs as observed during DLT-observation period

Secondary Outcome Measures

Measure:Immunogenicity: isatuximab
Time Frame:Up to 90 days following the last administration of study treatment (Up to approximately 27 months after first study treatment administration)
Safety Issue:
Description:Levels of anti-drug antibody against isatuximab
Measure:Immunogenicity: atezolizumab
Time Frame:Up to 30 days following the last administration of study treatment (Up to approximately 25 months after first study treatment administration)
Safety Issue:
Description:Levels of anti-drug antibody against atezolizumab
Measure:Tumor burden change
Time Frame:Up to 12 months after last patient's first treatment in a given cohort
Safety Issue:
Description: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 in participants with HCC, SCCHN and EOC, and in a sum of products of diameters for all target lesions in participants with GBM
Measure:Disease control rate
Time Frame:Up to 12 months after last patient's first treatment in a given cohort
Safety Issue:
Description:The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
Measure:Duration of response
Time Frame:Up to 12 months after last patient's first treatment in a given cohort
Safety Issue:
Description:The time from the date of the first response (PR or CR in radiographic objective response) that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first.
Measure:Progress free survival
Time Frame:Up to 12 months after last patient's first treatment in a given cohort
Safety Issue:
Description:The time from the first study treatment administration to the date of first documentation of progressive disease (RECIST 1.1 for participants with HCC, SCCHN, EOC and RANO criteria for participants with GBM) or the date of death from any cause
Measure:Response Rate
Time Frame:Up to 12 months after last patient's first treatment in a given cohort
Safety Issue:
Description:In GBM assessed by RANO criteria
Measure:Pharmacokinetic (PK) parameters: Area under the curve (AUC0-T)
Time Frame:From pre-isatuximab-dose on Cycle 1 Day 1 to 168 hours after start of isatuximab dose on Cycle 1 Day 1 (duration of assessment: 7 days; overall cycle duration: 21 days)
Safety Issue:
Description:AUC0-T is the area under the plasma concentration versus time curve calculated using the trapezoidal method over the dosing interval (T; i.e., 7 days for isatuximab) after the first infusion.
Measure:Assessment of PK parameter: Cmax
Time Frame:From pre-isatuximab-dose on Cycle 1 Day 1 to 168 hours after start of isatuximab dose on Cycle 1 Day 1 (duration of assessment: 7 days; overall cycle duration: 21 days)
Safety Issue:
Description:Cmax is maximum drug concentration observed
Measure:Assessment of PK parameter: tmax
Time Frame:From pre-isatuximab-dose on Cycle 1 Day 1 to 168 hours after start of isatuximab dose on Cycle 1 Day 1 (duration of assessment: 7 days; overall cycle duration: 21 days)
Safety Issue:
Description:Time to reach Cmax

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

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