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

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ClinicalTrials.gov Identifier: NCT03637764
Recruitment Status : Active, not recruiting
First Posted : August 20, 2018
Last Update Posted : November 25, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE August 5, 2018
First Posted Date  ICMJE August 20, 2018
Last Update Posted Date November 25, 2020
Actual Study Start Date  ICMJE August 6, 2018
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 3 weeks after first study treatment administration ]
    DLTs as observed during DLT-observation period
  • Adverse events (AEs) [ Time Frame: Up to 90 days after last study treatment administration (Up to approximately 27 months after first study treatment administration) ]
    Number of patients with AEs based on standard and systematic assessment including changes in laboratory tests and vital signs, according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 Grade scaling
  • Maximum tolerated dose (MTD) [ Time Frame: Up to 3 weeks after first study treatment administration ]
    MTD determined during Phase 1
  • Recommended Phase 2 dose (RP2D) [ Time Frame: Up to 3 weeks after first study treatment administration ]
    Dose selected for the Phase 2 portion
  • Response Rate [ Time Frame: Up to 6 months after last patient's first treatment in a given cohort ]
    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) assessed by using RECIST 1.1
  • Progression free survival [ Time Frame: Up to 6 months after last patient's first treatment ]
    In patients with glioblastoma multiforme (GBM) assessed by using Response Assessment for Neuro-Oncology (RANO) criteria at 6 months
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2018)
  • 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) ]
    Levels of anti-drug antibody against isatuximab
  • 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) ]
    Levels of anti-drug antibody against atezolizumab
  • Tumor burden change [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    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
  • Disease control rate [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
  • Duration of response [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    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.
  • Progress free survival [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    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
  • Response Rate [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    In GBM assessed by RANO criteria
  • 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) ]
    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.
  • 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) ]
    Cmax is maximum drug concentration observed
  • 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) ]
    Time to reach Cmax
Original Secondary Outcome Measures  ICMJE
 (submitted: August 16, 2018)
  • 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) ]
    Levels of anti-drug antibody against isatuximab
  • 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) ]
    Levels of anti-drug antibody against atezolizumab
  • Tumor burden change [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    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
  • Disease control rate [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    The sum of complete responses (CR) + partial responses (PR) + stable disease (SD)
  • Duration of response [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    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.
  • Progress free survival [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    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
  • Response Rate [ Time Frame: Up to 12 months after last patient's first treatment in a given cohort ]
    In GBM assessed by RANO criteria
  • 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) ]
    AUC 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).
  • 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) ]
    Cmax is maximum drug concentration observed
  • 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) ]
    Time to reach Cmax
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Preliminary Efficacy and PK of Isatuximab (SAR650984) Alone or in Combination With Atezolizumab in Patients With Advanced Malignancies
Official Title  ICMJE 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
Brief Summary

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasm
Intervention  ICMJE
  • Drug: Isatuximab SAR650984

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous

    Other Name: Sarclisa
  • Drug: Atezolizumab

    Pharmaceutical form: solution for infusion

    Route of administration: intravenous

    Other Name: Tecentriq®
Study Arms  ICMJE
  • Experimental: Phase1

    Isatuximab 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

    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Atezolizumab
  • Experimental: Phase2-Cohort A: HCC
    Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Atezolizumab
  • Experimental: Phase2-Cohort B: SCCHN
    Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Atezolizumab
  • Experimental: Phase2-Cohort C: EOC
    Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Atezolizumab
  • Experimental: Phase2-Cohort D-1:GBM
    Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W
    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Atezolizumab
  • Experimental: Phase2-Cohort D-2: GBM, isatuximab monotherapy
    Isatuximab dose 2
    Intervention: Drug: Isatuximab SAR650984
  • Experimental: Phase2-Cohort E
    Isatuximab 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
    Interventions:
    • Drug: Isatuximab SAR650984
    • Drug: Atezolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 16, 2018)
350
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Czechia,   France,   Greece,   Italy,   Netherlands,   Spain,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03637764
Other Study ID Numbers  ICMJE ACT15377
2018-000390-67 ( EudraCT Number )
U1111-1202-0839 ( Other Identifier: UTN )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.clinicalstudydatarequest.com/
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP