Clinical Trials /

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

NCT04524689

Description:

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

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: SAR408701 in Combination With Pembrolizumab and Pembrolizumab Alone in Patients With Non-squamous Non-small Cell Lung Cancer (NSQ NSCLC)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: ACT16146
  • SECONDARY ID: U1111-1233-9798
  • NCT ID: NCT04524689

Conditions

  • Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC)

Interventions

DrugSynonymsArms
SAR408701SAR408701 + Pembrolizumab
PembrolizumabPembrolizumab

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
SAR408701 + PembrolizumabExperimentalPembrolizumab will be administered intravenously prior to intravenously adminstration of SAR408701 every 3 weeks
  • SAR408701
  • Pembrolizumab
PembrolizumabActive ComparatorPembrolizumab - Pembrolizumab will be administered intravenously every 3 weeks. - Type:
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Study drug-related dose-limiting toxicity (DLTs) at Cycle 1 (C1D1 to C1D21), including but not limited to corneal toxicity

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:TEAEs, SAEs and laboratory abnormalities according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5 -
Measure:Duration of response
Time Frame:Baseline up to 10 months after last participant treated
Safety Issue:
Description: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
Measure:Progression-free survival
Time Frame:Baseline up to 10 months after last participant treated
Safety Issue:
Description: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
Measure:Ceoi of SAR408701 and pembrolizumab
Time Frame:Baseline up to 10 months after last participant treated
Safety Issue:
Description:Concentration observed at the end of IV infusion (Ceoi) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Measure:Cmax of SAR408701 and pembrolizumab
Time Frame:Baseline up to 10 months after last participant treated
Safety Issue:
Description:Maximum concentration observed after infusion (Cmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Measure:Tmax of SAR408701 and pembrolizumab
Time Frame:Baseline up to 10 months after last participant treated
Safety Issue:
Description:Time to reach Cmax (Tmax) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Measure:Clast of SAR408701 and pembrolizumab
Time Frame:Baseline up to 10 months after last participant treated -
Safety Issue:
Description: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
Measure:Tlast of SAR408701 and pembrolizumab
Time Frame:Baseline up to 10 months after last participant treated -
Safety Issue:
Description:Time of Clast (Tlast) of SAR408701 and pembrolizumab when given in combination and Ceoi of pembrolizumab when given alone
Measure:Ctrough of SAR408701 and pembrolizumab
Time Frame:Baseline up to 10 months after last participant treated
Safety Issue:
Description: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
Measure: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) -
Safety Issue:
Description: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
Measure:Incidence of anti-therapeutic antibodies (ATAs) against SAR408701
Time Frame:Baseline up to end of study (approximately 2 years)
Safety Issue:
Description:Incidence of anti-therapeutic antibodies (ATAs) against SAR408701

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sanofi

Last Updated

August 20, 2020