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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 : Recruiting
First Posted : August 20, 2018
Last Update Posted : December 10, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

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
Neoplasm Drug: Isatuximab SAR650984 Drug: Atezolizumab 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 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 : August 6, 2018
Estimated Primary Completion Date : September 14, 2022
Estimated Study Completion Date : September 14, 2022

Resource links provided by the National Library of Medicine


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


Drug: Atezolizumab

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Name: 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


Drug: Atezolizumab

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Name: 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


Drug: Atezolizumab

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Name: 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


Drug: Atezolizumab

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Name: 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


Drug: Atezolizumab

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Name: Tecentriq®

Experimental: Phase2-Cohort D-2: GBM, isatuximab monotherapy
Isatuximab dose 2
Drug: Isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


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


Drug: Atezolizumab

Pharmaceutical form: solution for infusion

Route of administration: intravenous

Other Name: Tecentriq®




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 3 weeks after first study treatment administration ]
    DLTs as observed during DLT-observation period

  2. 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

  3. Maximum tolerated dose (MTD) [ Time Frame: Up to 3 weeks after first study treatment administration ]
    MTD determined during Phase 1

  4. Recommended Phase 2 dose (RP2D) [ Time Frame: Up to 3 weeks after first study treatment administration ]
    Dose selected for the Phase 2 portion

  5. 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

  6. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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)

  5. 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.

  6. 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

  7. Response Rate [ Time Frame: 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) [ 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.

  9. 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

  10. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 and failed 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.
  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03637764


Contacts
Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # /or Contact-US@sanofi.com

Locations
United States, California
Investigational Site Number 8400004 Recruiting
Santa Monica, California, United States, 90404
United States, Massachusetts
Investigational Site Number 8400007 Recruiting
Boston, Massachusetts, United States, 02115
Investigational Site Number 8400107 Recruiting
Boston, Massachusetts, United States, 02215
United States, New Jersey
Investigational Site Number 8400001 Recruiting
Hackensack, New Jersey, United States, 07601
United States, Texas
Investigational Site Number 8400002 Recruiting
Houston, Texas, United States, 77030
Belgium
Investigational Site Number 0560001 Recruiting
Bruxelles, Belgium, 1200
Investigational Site Number 0560002 Recruiting
Gent, Belgium, 9000
Canada
Investigational Site Number 1240001 Recruiting
Toronto, Canada, M5G 2M9
Czechia
Investigational Site Number 2030001 Recruiting
Brno, Czechia, 65653
Italy
Investigational Site Number 3800006 Recruiting
Napoli, Italy, 80131
Investigational Site Number 3800003 Recruiting
Rozzano, Italy, 20089
Netherlands
Investigational Site Number 5280001 Recruiting
Rotterdam, Netherlands, 3015 GD
Spain
Investigational Site Number 7240001 Recruiting
Barcelona, Spain, 08035
Investigational Site Number 7240006 Recruiting
Hospitalet De Llobregat, Spain, 08907
Investigational Site Number 7240003 Recruiting
Madrid, Spain, 28040
Investigational Site Number 7240004 Recruiting
Madrid, Spain, 28050
Taiwan
Investigational Site Number 1580005 Recruiting
Kaohsiung, Taiwan, 807
Investigational Site Number 1580002 Recruiting
Tainan, Taiwan, 704
Investigational Site Number 1580001 Recruiting
Taipei 100, Taiwan
Investigational Site Number 1580003 Recruiting
Taipei, Taiwan, 104
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03637764     History of Changes
Other Study ID Numbers: ACT15377
2018-000390-67 ( EudraCT Number )
U1111-1202-0839 ( Other Identifier: UTN )
First Posted: August 20, 2018    Key Record Dates
Last Update Posted: December 10, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
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/

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs