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SAR408701 in Combination With Pembrolizumab and Pembrolizumab Alone in Patients With Non-squamous Non-small Cell Lung Cancer (NSQ NSCLC) (CARMEN-LC05)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04524689
Recruitment Status : Recruiting
First Posted : August 24, 2020
Last Update Posted : December 8, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE August 20, 2020
First Posted Date  ICMJE August 24, 2020
Last Update Posted Date December 8, 2020
Actual Study Start Date  ICMJE October 26, 2020
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
  • Part 1: Number of participants with study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21) [ Time Frame: Baseline up to 10 months after last participant treated ]
    Study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21), including but not limited to corneal toxicity
  • Part 2: Objective response rate (ORR) of SAR408701 + pembrolizumab and pembrolizumab single agent - [ Time Frame: Baseline up to 10 months after last participant treated ]
    ORR is defined as proportion of participants who have a confirmed complete response (CR) or partial response (PR) as per response evaluation criteria in solid tumors (RECIST v1.1)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2020)
  • Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and laboratory abnormalities [ Time Frame: Baseline up to 10 months after last participant treated ]
    TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5 -
  • Duration of response [ Time Frame: Baseline up to 10 months after last participant treated ]
    Duration of response (DOR), defined as the time from first documented evidence of CR or PR until progressive disease determined per RECIST 1.1 or death from any cause, whichever occurs first
  • Progression-free survival [ Time Frame: Baseline up to 10 months after last participant treated ]
    Progression-free survival, defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause, whichever comes first
  • Ceoi of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated ]
    Concentration observed at the end of IV infusion (Ceoi) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
  • Cmax of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated ]
    Maximum concentration observed after infusion (Cmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
  • Tmax of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated ]
    Time to reach Cmax (Tmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
  • Clast of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated - ]
    Clast concentration observed above the lower limit of quantification after infusion (Clast)of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
  • Tlast of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated - ]
    Time of Clast (Tlast) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
  • Ctrough of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated ]
    Concentration observed just before treatment administration during repeated dosing (Ctrough) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
  • AUC0-21d of SAR408701 and pembrolizumab [ Time Frame: Baseline up to 10 months after last participant treated - 11. Baseline up to end of study (approximately 2 years) - ]
    Area under the plasma concentration versus time curve calculated using the trapezoidal method from time 0 to 21 days (AUC 0-21d) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
  • Incidence of anti-therapeutic antibodies (ATAs) against SAR408701 [ Time Frame: Baseline up to end of study (approximately 2 years) ]
    Incidence of anti-therapeutic antibodies (ATAs) against SAR408701
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SAR408701 in Combination With Pembrolizumab and Pembrolizumab Alone in Patients With Non-squamous Non-small Cell Lung Cancer (NSQ NSCLC)
Official Title  ICMJE Randomized, Open-label, Phase 2 Study of SAR408701 Combined With Pembrolizumab and Pembrolizumab Alone in Patients With CEACAM5 and PD-L1 Positive Advanced/Metastatic Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Brief Summary

Primary Objectives:

  • Part 1 (safety run-in): To assess the tolerability and to confirm the recommended dose of SAR408701 in combination with pembrolizumab in the NSQ NSCLC population
  • Part 2: To assess the antitumor activity of SAR408701 in combination with pembrolizumab and pembrolizumab single agent in the NSQ NSCLC population

Secondary Objective:

  • To assess the safety and tolerability of SAR408701 in combination with pembrolizumab and pembrolizumab single agent
  • To assess the durability of the response to treatment with SAR408701 in combination with pembrolizumab and pembrolizumab single agent
  • To assess the efficacy on progression-free survival (PFS) of SAR408701 in combination with pembrolizumab and pembrolizumab single agent
  • To assess the pharmacokinetics (PK) of SAR408701 and pembrolizumab when given in combination, and of pembrolizumab when given as a single agent
  • To assess the immunogenicity of SAR408701 when given in combination with pembrolizumab
Detailed Description The expected duration of the study intervention for participants may vary based on progression date; median expected duration of study per participant is estimated 11 months (up to 1 month for screening, a median of 6 months for treatment, and a median of 4 months for end-of-treatment assessments and safety follow-up visit).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)
Intervention  ICMJE
  • Drug: SAR408701
    Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
  • Drug: Pembrolizumab
    Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous
Study Arms  ICMJE
  • Experimental: SAR408701 + Pembrolizumab
    Pembrolizumab will be administered intravenously prior to intravenously adminstration of SAR408701 every 3 weeks
    Interventions:
    • Drug: SAR408701
    • Drug: Pembrolizumab
  • Active Comparator: Pembrolizumab
    Pembrolizumab - Pembrolizumab will be administered intravenously every 3 weeks. - Type:
    Intervention: Drug: Pembrolizumab
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 20, 2020)
54
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSQ NSCLC with no EGFR sensitizing mutation or BRAF mutation or ALK/ROS alterations.
  • No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease).
  • Expression of CEACAM5 as demonstrated prospectively by a centrally assessed Immunohistochemistry (IHC) assay of ≥2+ in intensity involving at least 50% of the tumor cell population in archival tumor sample (or if not available fresh biopsy sample).
  • PD-L1 positive tumor (TPS ≥1%) as determined locally by an approved test
  • Measurable disease based on RECIST 1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
  • Capable of giving signed informed consent

Exclusion criteria:

  • Medical condition requiring concomitant administration of a medication with a narrow therapeutic window and metabolized by CYP450 or a strong CTP3A inhibitor.
  • Untreated brain metastases and history of leptomeningeal disease.
  • Significant concomitant illness, including any severe medical condition that, in the opinion of the investigator or Sponsor, would impair the patient's participation in the study or interpretation of the results.
  • History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
  • History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known HIV disease requiring antiretroviral treatment, or active hepatitis A, B, or C infection.
  • History of active autoimmune disease that has required systemic treatment in the past 2 years.
  • History of allogeneic tissue/solid organ transplantation.
  • Active infection requiring IV systemic therapy within 2 weeks prior to randomization or active tuberculosis.
  • Interstitial lung disease or history of pneumonitis that has required oral or IV steroids
  • Non-resolution of any prior treatment-related toxicity to ≥ Grade 2 according to NCI CTCAE V5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy.
  • Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. The use of contact lenses is not permitted.
  • Symptomatic herpes zoster within 3 months prior to screening.
  • Significant allergies to humanized monoclonal antibodies.
  • Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
  • Concurrent treatment with any other anticancer therapy.
  • Have received prior chemotherapy treatment for advanced/metastatic NSCLC.
  • The patient is a candidate for a curative treatment with either surgical resection and/or chemoradiation
  • Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is longer, for any investigational treatment).
  • Any prior therapy targeting CEACAM5.
  • Any prior treatment with any other anti-PD-1, or PD-L1 or programmed death ligand 2 (PD-L2), anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4.
  • Any prior maytansinoid treatment (DM1 or DM4 ADC).
  • Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication. Daily steroid replacement therapy or any corticosteroid premedication if applicable are allowed.
  • Any radiation therapy to lung >30 Gy within 6 months of first study intervention administration.
  • Has received or will receive a live vaccine within 30 days prior to the first study intervention administration.
  • Any major surgery within the preceding 3 weeks of the first study intervention administration.

Prior/concurrent clinical study experience

  • Current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
  • 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: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com
Listed Location Countries  ICMJE Australia,   Chile,   France,   Hungary,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04524689
Other Study ID Numbers  ICMJE ACT16146
U1111-1233-9798 ( Other Identifier: UTN )
Has Data Monitoring Committee No
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 December 2020

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