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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 : November 10, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi

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

Condition or disease Intervention/treatment Phase
Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) Drug: SAR408701 Drug: Pembrolizumab Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : October 26, 2020
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SAR408701 + Pembrolizumab
Pembrolizumab will be administered intravenously prior to intravenously adminstration of SAR408701 every 3 weeks
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

Active Comparator: Pembrolizumab
Pembrolizumab - Pembrolizumab will be administered intravenously every 3 weeks. - Type:
Drug: Pembrolizumab
Pharmaceutical form:Concentrate for solution for infusion Route of administration: Intravenous




Primary Outcome Measures :
  1. 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

  2. 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)


Secondary Outcome Measures :
  1. 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 -

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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



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.


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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 :

  • 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.


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): NCT04524689


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext option 6 Contact-US@sanofi.com

Locations
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Australia
Investigational Site Number 0360001 Recruiting
Heidelberg West, Australia, 3081
Investigational Site Number 0360003 Recruiting
Macquarie Park, Australia, 2109
Chile
Investigational Site Number 1520002 Recruiting
Santiago, Chile, 7500713
Investigational Site Number 1520001 Recruiting
Santiago, Chile, 8420383
Investigational Site Number 1520003 Recruiting
Viña Del Mar, Chile, 2520598
France
Investigational Site Number 2500001 Recruiting
Pessac, France, 33604
Investigational Site Number 2500004 Recruiting
Poitiers Cedex, France, 86021
Hungary
Investigational Site Number 3480002 Recruiting
Budapest, Hungary, 1122
Investigational Site Number 3480004 Recruiting
Farkasgyepü, Hungary, 8582
Spain
Investigational Site Number 7240001 Recruiting
Madrid, Spain, 28041
Investigational Site Number 7240003 Recruiting
Valencia, Spain, 46010
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: NCT04524689    
Other Study ID Numbers: ACT16146
U1111-1233-9798 ( Other Identifier: UTN )
First Posted: August 24, 2020    Key Record Dates
Last Update Posted: November 10, 2020
Last Verified: November 2020
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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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents