Clinical Trials /

SAR408701 in Combination With Ramucirumab in Pre-treated Patients With Non Squamous Non-small Cell Lung Cancer (NSQ NSCLC)

NCT04394624

Description:

Primary Objectives: o Part 1 (safety run-in): To assess the tolerability and to confirm the recommended dose of SAR408701 in combination with ramucirumab in the NSQ NSCLC population. o Part 2: To assess the antitumor activity of SAR408701 in combination with ramucirumab in the NSQ NSCLC population. Secondary Objectives: - To assess the safety and tolerability of SAR408701 in combination with ramucirumab - To assess the durability of the response to treatment with SAR408701 in combination with ramucirumab - To assess efficacy of SAR408701 in combination with ramucirumab on progression free survival - To assess the pharmacokinetic (PK) profile of SAR408701 and ramucirumab when given in combination - To assess the immunogenicity of SAR408701 when given in combination with ramucirumab

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: SAR408701 in Combination With Ramucirumab in Pre-treated Patients With Non Squamous Non-small Cell Lung Cancer (NSQ NSCLC)
  • Official Title: Open-label, Single-arm Trial to Evaluate Antitumor Activity, Safety, and Pharmacokinetics of SAR408701 Used in Combination With Ramucirumab in Metastatic, Non-squamous, Non-small-cell Lung Cancer (NSQ NSCLC) Patients With CEACAM5-positive Tumors, Previously Treated With Platinum-based Chemotherapy and an Immune Checkpoint Inhibitor

Clinical Trial IDs

  • ORG STUDY ID: ACT16525
  • SECONDARY ID: 2019-003914-15
  • SECONDARY ID: U1111-1244-1585
  • NCT ID: NCT04394624

Conditions

  • Non-small Cell Lung Cancer Metastatic

Interventions

DrugSynonymsArms
SAR408701Ramucirumab + SAR408701
ramucirumabRamucirumab + SAR408701

Purpose

Primary Objectives: o Part 1 (safety run-in): To assess the tolerability and to confirm the recommended dose of SAR408701 in combination with ramucirumab in the NSQ NSCLC population. o Part 2: To assess the antitumor activity of SAR408701 in combination with ramucirumab in the NSQ NSCLC population. Secondary Objectives: - To assess the safety and tolerability of SAR408701 in combination with ramucirumab - To assess the durability of the response to treatment with SAR408701 in combination with ramucirumab - To assess efficacy of SAR408701 in combination with ramucirumab on progression free survival - To assess the pharmacokinetic (PK) profile of SAR408701 and ramucirumab when given in combination - To assess the immunogenicity of SAR408701 when given in combination with ramucirumab

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
Ramucirumab + SAR408701ExperimentalRamucirumab will be administered intravenously prior to intravenously adminstration of SAR408701 every two 2 weeks.
  • SAR408701
  • ramucirumab

Eligibility Criteria

        Inclusion criteria :

          -  Metastatic disease progression fulfilling both of the following 2 criteria:

               1. Having progressive disease during or after platinum-based chemotherapy (at least
                  2 cycles). Maintenance therapy following platinum-based chemotherapy is not
                  considered as a separate regimen. Adjuvant/neoadjuvant treatment for a patient
                  who had a relapse with metastatic disease during or within 6 months of completing
                  treatment will be considered as first-line treatment.

                  AND

               2. Having progressive disease during or after 1 immune checkpoint inhibitor
                  (anti-PD1/PD-L1); this could be given as monotherapy or in combination with
                  platinum-based chemotherapy (whatever the order).

          -  Participants with carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5
             expression of ≥2+ in archival tumor sample (or if not available, fresh biopsy sample)
             involving at least 50 % of the tumor cell population as demonstrated prospectively by
             central laboratory via immune histochemistry (IHC).

          -  At least one measurable lesion by RECIST v1.1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

          -  A female participant who agrees to use effective contraceptive methods during and for
             at least 7 months after the last dose of study intervention.

          -  A male participant who agrees to use effective contraception methods during and for at
             least 4 months after the last dose of study intervention

          -  Signed informed consent

        Exclusion criteria:

        Participants are excluded from the study if any of the following criteria apply:

          -  Patients with untreated brain metastases and history of leptomeningeal disease.

          -  Significant concomitant illnesses that 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.

          -  Non-resolution of any prior treatment related toxicity to < grade 2 according to NCI
             CTCAE V5.0, except for alopecia, vitiligo and active thyroiditis controlled with
             hormonal replacement therapy

          -  History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known
             HIV disease requiring antiretroviral treatment, or unresolved viral hepatitis

          -  Previous history of and/or unresolved corneal disorders. The use of contact lenses is
             not permitted.

          -  Radiographic evidence of major airway or blood vessel invasion or intratumor
             cavitation

          -  History of uncontrolled hereditary or acquired thrombotic disorder or history of
             aneurism.

          -  Major surgery within 28 days prior to Day 1/first IMP infusion,. Postoperative
             bleeding complications or wound complications from a surgical procedure performed in
             the last 2 months.

          -  History of gross hemoptysis within 2 months before the first administration of study
             intervention.

          -  Clinically relevant congestive heart failure (CHF; NYHA II-IV, or LVEF less than 50%)
             or symptomatic or poorly controlled cardiac arrhythmia.

          -  Any arterial thrombotic event within 6 months before the first administration of study
             intervention.

          -  Uncontrolled arterial hypertension (systolic ≥150 mmHg or diastolic ≥90 mmHg) despite
             standard medical management.

          -  Serious or nonhealing wound, skin ulcer, or bone fracture within 28 days before the
             first administration of study intervention.

          -  Gastrointestinal (GI) perforation and/or fistulae within 6 months prior to first
             administration of study intervention.

          -  Significant bleeding disorders, vasculitis, or Grade 3-4 gastrointestinal (GI)
             bleeding within 3 months before the first administration of study intervention.

          -  Bowel obstruction, history or presence of inflammatory enteropathy or extensive
             intestinal resection Crohn's disease, ulcerative colitis, or chronic diarrhea.

          -  Medical condition requiring concomitant administration of a medication with a narrow
             therapeutic window and metabolized by CYP450 or a strong CYP3A inhibitor

          -  Concurrent treatment with any other anticancer therapy

          -  No more than 1-line previous chemotherapy in metastatic setting

          -  Prior treatment with ramucirumab or docetaxel

          -  Prior therapy targeting CEACAM5 or maytansinoid treatment (DM1 or DM4 antibody-drug
             conjugate)

          -  Contraindication to use of corticosteroid premedication

          -  Current therapeutic anticoagulation with warfarin, low-molecular-weight heparin, or
             similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are
             eligible

          -  Previous enrollment in this study, current participation in any other clinical study
             involving an investigational study treatment, or any other type of medical research

          -  Poor bone marrow, liver or kidney functions

          -  Urine dipstick or routine analysis indicating proteinuria of 2+ or higher, unless a 24
             hour urine collection demonstrates <1000 mg of protein.

          -  Sensitivity to any of the study interventions, or components thereof, or drug or other
             allergy that, in the opinion of the Investigator, contraindicates participation in the
             study.Most important exclusion criteria for potential participants

        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: Incidence of study drug-related dose-limiting toxicity (DLT) at Cycle 1 and Cycle 2
Time Frame:baseline up to Cycle 2 (approximatively 1 month)
Safety Issue:
Description:Drug-related dose-limiting toxicity (DLT) as observed during DLT-observation period tolerability in order to confirm the recommended dose of SAR408701 in combination with ramucirumab for the Part 2.

Secondary Outcome Measures

Measure:Incidence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)
Time Frame:Baseline up to 90 days after the last study treatment administration
Safety Issue:
Description:Incidence of TEAEs and SAEs and laboratory abnormalities according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5.0.
Measure:Duration of response (DOR)
Time Frame:Baseline up to 6 months after the last patient treated
Safety Issue:
Description:Duration of response (DOR) is defined as the time from first documented evidence of CR or PR until progressive disease (PD) determined per RECIST v.1.1 or death from any cause, whichever occurs first.
Measure:Progression-free survival (PFS)
Time Frame:Baseline up to 6 months after the last patient treated
Safety Issue:
Description:Progression-free survival (PFS) is defined as the time from the first investigational medicinal product (IMP) administration to the date of the first documented disease progression or death due to any cause, whichever comes first.
Measure:PK - Cmax of SAR408701
Time Frame:Cycle 1 (each cycle = 2 weeks)
Safety Issue:
Description:Maximum concentration (Cmax) of SAR408701 observed after SAR408701 1st infusion.
Measure:PK - AUC0-14d of SAR408701
Time Frame:Cycle 1 (each cycle=2 weeks)
Safety Issue:
Description:Area under the plasma SAR408701 concentration versus time curve calculated using the trapezoidal method from time 0 to 14 days (AUC0-14d) after SAR408701 1st infusion.
Measure:PK - Ctrough of SAR408701
Time Frame:Baseline up to cycle 13 (each cycle= 2 weeks)
Safety Issue:
Description:Concentration observed of SAR408701 just before SAR408701 treatment administration during repeated dosing.
Measure:Ctrough of ramucirumab
Time Frame:Baseline to cycle 7 (each cycle= 2 weeks)
Safety Issue:
Description:Concentration observed of ramucirumab just before ramucirumab treatment administration during repeated dosing.
Measure:Incidence of anti-therapeutic antibodies (ATAs) against SAR408701
Time Frame:Baseline up to end of treatment (approximately 6 months)
Safety Issue:
Description:Incidence of anti-therapeutic antibodies (ATAs) against SAR408701.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

Last Updated

April 8, 2021