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

Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT03637764
Collaborator
(none)
107
Enrollment
27
Locations
7
Arms
45.1
Actual Duration (Months)
4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
107 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 6, 2018
Actual Primary Completion Date :
May 11, 2022
Actual Study Completion Date :
May 11, 2022

Arms and Interventions

Arm Intervention/Treatment
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

Drug: Isatuximab SAR650984
Pharmaceutical form: solution for infusion Route of administration: intravenous
Other Names:
  • Sarclisa

    • Drug: Atezolizumab
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Tecentriq®

    		•
    Experimental: Phase2-Cohort A: HCC

    Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W

    Drug: Isatuximab SAR650984
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Sarclisa

    • Drug: Atezolizumab
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Tecentriq®

    		•
    Experimental: Phase2-Cohort B: SCCHN

    Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W

    Drug: Isatuximab SAR650984
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Sarclisa

    • Drug: Atezolizumab
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Tecentriq®

    		•
    Experimental: Phase2-Cohort C: EOC

    Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W

    Drug: Isatuximab SAR650984
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Sarclisa

    • Drug: Atezolizumab
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Tecentriq®

    		•
    Experimental: Phase2-Cohort D-1:GBM

    Isatuximab and atezolizumab combination: Isatuximab dose determined in Phase 1 part of study and atezolizumab predefined dose Q3W

    Drug: Isatuximab SAR650984
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Sarclisa

    • Drug: Atezolizumab
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Tecentriq®

    		•
    Experimental: Phase2-Cohort D-2: GBM, isatuximab monotherapy

    Isatuximab dose 2

    Drug: Isatuximab SAR650984
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Sarclisa

    		•
    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

    Drug: Isatuximab SAR650984
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Sarclisa

    • Drug: Atezolizumab
    Pharmaceutical form: solution for infusion Route of administration: intravenous
    Other Names:
  • Tecentriq®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose Limiting Toxicities (DLTs) [Up to 3 weeks after first study treatment administration]

      DLTs as observed during DLT-observation period

    2. Adverse events (AEs) [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

    3. Maximum tolerated dose (MTD) [Up to 3 weeks after first study treatment administration]

      MTD determined during Phase 1

    4. Recommended Phase 2 dose (RP2D) [Up to 3 weeks after first study treatment administration]

      Dose selected for the Phase 2 portion

    5. Response Rate [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

    6. Progression free survival [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

    Secondary Outcome Measures

    1. Immunogenicity: isatuximab [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

    2. Immunogenicity: atezolizumab [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

    3. Tumor burden change [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

    4. Disease control rate [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)

    5. Duration of response [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.

    6. Progress free survival [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

    7. Response Rate [Up to 12 months after last patient's first treatment in a given cohort]

      In GBM assessed by RANO criteria

    8. Pharmacokinetic (PK) parameters: Area under the curve (AUC0-T) [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.

    9. Assessment of PK parameter: Cmax [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

    10. Assessment of PK parameter: tmax [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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Investigational Site Number :8400004 Santa Monica California United States 90404
    2 Investigational Site Number :8400207 Boston Massachusetts United States 02114
    3 Investigational Site Number :8400007 Boston Massachusetts United States 02115
    4 Investigational Site Number :8400002 Houston Texas United States 77030
    5 Investigational Site Number :0560001 Bruxelles Belgium 1200
    6 Investigational Site Number :0560002 Gent Belgium 9000
    7 Investigational Site Number :1240001 Toronto Ontario Canada M5G 2M9
    8 Investigational Site Number :2030001 Brno Czechia 65653
    9 Investigational Site Number :2030003 Olomouc Czechia 77900
    10 Investigational Site Number :2030002 Praha 2 Czechia 12808
    11 Investigational Site Number :3800007 Meldola Forlì-Cesena Italy 47014
    12 Investigational Site Number :3800003 Rozzano Milano Italy 20089
    13 Investigational Site Number :3800009 Milano Italy 20141
    14 Investigational Site Number :3800004 Padova Italy 35128
    15 Investigational Site Number :5280001 Rotterdam Netherlands 3015 CE
    16 Investigational Site Number :7240001 Barcelona Barcelona [Barcelona] Spain 08035
    17 Investigational Site Number :7240006 Hospitalet de Llobregat Castilla Y León Spain 08908
    18 Investigational Site Number :7240003 Madrid / Madrid Madrid, Comunidad De Spain 28040
    19 Investigational Site Number :7240004 Madrid Madrid, Comunidad De Spain 28050
    20 Investigational Site Number :7240008 Pamplona Navarra Spain 31008
    21 Investigational Site Number :7240007 Madrid Spain 28041
    22 Investigational Site Number :1580005 Kaohsiung Taiwan 807
    23 Investigational Site Number :1580002 Tainan Taiwan 704
    24 Investigational Site Number :1580001 Taipei 100 Taiwan
    25 Investigational Site Number :1580003 Taipei Taiwan 104
    26 Investigational Site Number :1580006 Taipei Taiwan 112
    27 Investigational Site Number :1580004 Taipei Taiwan 114

    Sponsors and Collaborators

    • Sanofi

    Investigators

    • Study Director: Clinical Sciences & Operations, Sanofi

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sanofi
    ClinicalTrials.gov Identifier:
    NCT03637764
    Other Study ID Numbers:
    • ACT15377
    • 2018-000390-67
    • U1111-1202-0839
    First Posted:
    Aug 20, 2018
    Last Update Posted:
    Jun 9, 2022
    Last Verified:
    Jun 8, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Sanofi
    Anti-CD38 monoclonal antibody
    Additional relevant MeSH terms:
    Neoplasms
    Atezolizumab

    Study Results

    No Results Posted as of Jun 9, 2022