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Isatuximab in Combination With REGN2810 (Cemiplimab) in Patients With Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT03367819
Recruitment Status : Recruiting
First Posted : December 11, 2017
Last Update Posted : March 26, 2019
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objectives:

  • To characterize the safety and tolerability of isatuximab in combination with REGN2810 in patients with metastatic, castration-resistant prostate cancer (mCRPC) who are naïve to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1)-containing therapy, or non-small cell lung cancer (NSCLC) who progressed on anti-PD-1/PD-L1-containing therapy, and to confirm the recommended Phase 2 dose (RP2D).
  • To assess the response rate of isatuximab in combination with REGN2810 in patients with either mCRPC who are anti-PD-1/PD-L1 therapy naive, or NSCLC who progressed on anti-PD-1/PD-L1 therapy, or of isatuximab as single agent in patients with mCRPC.

Secondary Objectives:

  • To evaluate the safety of the combination of isatuximab with REGN2810 or isatuximab monotherapy.
  • To evaluate the immunogenicity of isatuximab and REGN2810.
  • To characterize the pharmacokinetic (PK) profile of isatuximab single agent or in combination with REGN2810, and to characterize the PK of REGN2810 in combination with isatuximab.
  • To assess overall efficacy of isatuximab in combination with REGN2810 or as a single agent.

Condition or disease Intervention/treatment Phase
Prostate Cancer Non-small Cell Lung Cancer Drug: Isatuximab SAR650984 Drug: Cemiplimab REGN2810 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 134 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Random assignment used only for allocation to Cohort A-1 or A-2
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 REGN2810, or Isatuximab Alone, in Patients With Advanced Malignancies
Actual Study Start Date : January 4, 2018
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 1: mCRPC/NSCLC
Isatuximab dose 1 and REGN2810 predefined dose
Drug: Isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: Cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Experimental: Cohort A-1: mCRPC, isatuximab and REGN2810 combination
Patients with mCRPC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose
Drug: Isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: Cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Experimental: Cohort A-2: mCRPC, isatuximab monotherapy
Patients with mCRPC will be given isatuximab dose 2
Drug: Isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Experimental: Phase 2 Cohort B: NSCLC
Patients with NSCLC will be given isatuximab dose determined in Phase 1 arm of study and REGN2810 predefined dose
Drug: Isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: Cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Experimental: Phase 2 Cohort C: mCRPC
Isatuximab dose 3 will be given in combination with REGN2810 predefined dose or isatuximab dose 3 will be given as monotherapy in patients with mCRPC
Drug: Isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: Cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Experimental: Phase 2 Cohort D: NSCLC
Isatuximab dose 3 will be given in combination with REGN2810 predefined dose
Drug: Isatuximab SAR650984

Pharmaceutical form: solution for infusion

Route of administration: intravenous


Drug: Cemiplimab REGN2810

Pharmaceutical form: solution for infusion

Route of administration: intravenous





Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 3 weeks after first study treatment administration ]
    DLTs are following adverse events (AEs) in Cycle 1 unless due to disease progression or an obviously unrelated cause: Grade (G) 4 neutropenia >7 days; G 3 to 4 neutropenia with fever or documented infection; G 3 to 4 thrombocytopenia with bleeding requiring intervention; G 4 non-hematological AE; G ≥2 uveitis; G 3 non-hematological AE >3 days despite supportive care (with defined exceptions); Delay in initiation of the 2nd cycle >14 days for related laboratory abnormalities/AEs

  2. AEs [ Time Frame: Up to 30 days after last study treatment administration (Up to approximately 25 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. Response Rate [ Time Frame: Up to 12 months from last patient in ]
    In non-small cell lung cancer (NSCLC): assessed and objective responses by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; In metastatic castration-resistant prostate cancer (mCRPC): response will be defined per Prostate Cancer Working Group 3 (PCWG3) criteria


Secondary Outcome Measures :
  1. Immunogenicity: isatuximab [ Time Frame: Up to 90 days following the last administration of study treatment or until the sample is negative (Up to approximately 27 months after first study treatment administration) ]
    Levels of anti-drug antibody against isatuximab

  2. Pharmacokinetic (PK) parameters: area under the curve (AUC) [ Time Frame: Up to 3 weeks after first study treatment administration ]
    AUC is area under the drug concentration versus time curve

  3. Tumor burden change [ Time Frame: Up to 12 months from last patient in ]
    The best percent-change from baseline in a sum of the diameters for all target lesions

  4. Duration of response [ Time Frame: Up to 12 months from last patient in ]
    Defined as the time from the date of the first response that is subsequently confirmed to the date of first confirmed disease progression or death, whichever occurs first

  5. Progression-free survival [ Time Frame: Up to 12 months from last patient in ]
    Defined as time from the first study treatment administration to the date of first documentation of progressive disease that is subsequently confirmed or the date of death from any cause

  6. Assessment of PK parameter: Cmax [ Time Frame: Up to 3 weeks after first study treatment administration ]
    Cmax is maximum drug concentration observed

  7. Immunogenicity: REGN2810 [ Time Frame: Up to 90 days following the last administration of study treatment or until the sample is negative (Up to approximately 27 months after first study treatment administration) ]
    Levels of anti-drug antibody against REGN2810

  8. Disease control rate [ Time Frame: Up to 12 months from last patient in ]
    Defined as the proportion of patients with confirmed complete response or partial response or stable disease, as assessed by Investigator relative to the total number of patients in the analysis population



Information from the National Library of Medicine

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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 metastatic castration-resistant prostate cancer (mCRPC) or non-small cell lung cancer (NSCLC) with evidence of measurable disease.
  • Failure of, inability to, or refusal to receive standard of care.
  • ≥18 years of age.

Exclusion criteria:

  • Prior exposure to isatuximab or participation in clinical studies with isatuximab.
  • For patients with mCRPC, 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 hematologic transplant.
  • Eastern Cooperative Oncology Group performance status (PS) ≥2.
  • 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): NCT03367819


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

Locations
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United States, Alabama
Investigational Site Number 8400003 Recruiting
Birmingham, Alabama, United States, 35249
United States, California
Investigational Site Number 8400009 Recruiting
Santa Monica, California, United States, 90403
United States, Georgia
Investigational Site Number 8400007 Recruiting
Atlanta, Georgia, United States, 30322
United States, New Jersey
Investigational Site Number 8400002 Recruiting
Hackensack, New Jersey, United States, 07601
United States, Tennessee
Investigational Site Number 8400005 Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Investigational Site Number 8400004 Recruiting
Houston, Texas, United States, 77030
France
Investigational Site Number 2500002 Recruiting
Bordeaux Cedex, France, 33076
Investigational Site Number 2500001 Recruiting
Villejuif Cedex, France, 94805
Italy
Investigational Site Number 3800006 Recruiting
Napoli, Italy, 80131
Investigational Site Number 3800001 Recruiting
Orbassano, Italy, 10043
Investigational Site Number 3800004 Recruiting
Padova, Italy, 35128
Investigational Site Number 3800002 Recruiting
Pavia, Italy, 27100
Investigational Site Number 3800003 Recruiting
Rozzano, Italy, 20089
Investigational Site Number 3800005 Recruiting
Verona, Italy, 37134
Taiwan
Investigational Site Number 1580002 Recruiting
Tainan, Taiwan, 704
Investigational Site Number 1580001 Recruiting
Taipei 100, Taiwan
United Kingdom
Investigational Site Number 8260002 Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Investigational Site Number 8260001 Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03367819     History of Changes
Other Study ID Numbers: ACT15319
2017-002846-61 ( EudraCT Number )
U1111-1197-7792 ( Other Identifier: UTN )
First Posted: December 11, 2017    Key Record Dates
Last Update Posted: March 26, 2019
Last Verified: March 2019
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/

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

Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Cemiplimab
Antineoplastic Agents, Immunological
Antineoplastic Agents