A First-in-human Study of the Safety, Pharmacokinetics, Pharmacodynamics and Anti-tumor Activity of SAR439459 Monotherapy and Combination of SAR439459 and REGN2810 in Patients With Advanced Solid Tumors

Description

Primary Objectives: Dose escalation (Part 1) Part 1A (SAR439459 monotherapy) - To determine the maximum tolerated dose (MTD) and/or maximum administered dose (MAD) of SAR439459 when administered intravenously as monotherapy in adult patients with advanced solid tumors. Part 1B (SAR439459 and REGN2810 combination therapy) - To determine the MTD and/or MAD of SAR439459 administered intravenously in combination with REGN2810 administered intravenously in adult patients with advanced solid tumors. Dose expansion (Part 2) Part 2A (SAR439459 monotherapy) - To determine optimal dose of SAR439459 administered intravenously in adult patients with advanced melanoma who have failed a prior therapy based on anti-PD-1 (programmed cell death-1) or anti-PD-L1. Part 2B (SAR439459 and REGN2810 combination therapy) - To determine the objective response rate (ORR) of SAR439459 administered intravenously in combination with REGN2810 in adult patients with selected advanced solid tumors. Secondary Objectives: - To characterize the pharmacokinetic (PK) profile of SAR439459 administered as monotherapy (Part 1A/2A) and in combination with REGN2810 (Part 1B/2B) and PK profile of REGN2810 in combination with SAR439459 (Part 1B/2B). - To assess the immunogenicity of SAR439459 monotherapy (Part 1A/2A) and SAR439459 and REGN2810 combination (Part 1B/2B). Dose escalation (Part 1) - To characterize the overall safety and tolerability profile of SAR439459 administered as monotherapy and in combination with REGN2810. - To identify the preliminary recommended phase 2 dose (pRP2D) of SAR439459 as monotherapy or in combination with REGN2810. Dose expansion (Part 2) - To determine the progression free survival (PFS), time to progression (TTP), ORR, and safety of SAR439459 as monotherapy and PFS, TTP and safety in combination with REGN2810 in adult patients with selected advanced solid tumors. - To confirm the optimal dose of SAR439459 administered in combination with REGN2810 (Part 2).

Study Start Date

June, 09 2017

Estimated Completion Date

June 2021

Interventions

  • Biological: SAR439459
  • Drug: REGN2810

Study ID

Sanofi -- TCD14678

Status

Recruiting

Trial ID

NCT03192345

Study Type

Interventional

Trial Phase

Phase 1

Enrollment Quota

130

Sponsor

Sanofi

Inclusion criteria: Dose escalation (Part 1A and Part 1B)
  • Patients with histologically confirmed, advanced unresectable or metastatic solid tumor whom in the opinion of the Investigator does not have a suitable alternative therapy. Dose expansion (Part 2A)
  • Patients with histologically confirmed, advanced unresectable or metastatic melanoma whom in the opinion of the Investigator does not have a suitable alternative therapy.
  • Patients must have failed a prior therapy based on anti-PD-1 or anti-PD-L1 as defined by disease progression confirmed radiologically within 12 weeks of commencing treatment without any evidence of a response.
  • Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy. Patients must be able to provide mandatory tumor biopsies prior to and during study treatment. Dose expansion (Part 2B)
  • Patients with histologically confirmed advanced unresectable or metastatic melanoma who have failed a prior therapy based on anti-PD-1 or anti-PD-L1 or patients with a specific type of colorectal adenocarcinoma who have progressed after last line of therapy and have no other alternative approved standard therapy or refuse approved standard therapy. All cohorts
  • At least 1 measurable lesion by RECIST v1.1.
  • Patient understands and has signed Informed Consent form and is willing and able to comply with the requirements of the trial. Exclusion criteria:
  • Age <18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status >1.
  • Concurrent treatment with any other anticancer therapy (including radiotherapy or investigational agents) or participation in another clinical study.
  • Washout period of less than 3 weeks to prior anticancer therapy.
  • Women of reproductive potential and male subjects with female partners of childbearing potential who are not willing to avoid pregnancy by using effective contraceptive.
  • Pregnant or breast-feeding women.
  • Unwillingness and inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
  • Significant and uncontrolled concomitant illness, including any psychiatric condition.
  • Active infections, including unexplained fever (temperature >38.1ÂșC), or antibiotic therapy within 1 week prior to enrollment.
  • Any prior organ transplant including allogeneic bone marrow transplant.
  • History within the last 5 years of an invasive malignancy other than the one treated in this study.
  • History of known human immunodeficiency virus (HIV), unresolved viral hepatitis.
  • Any major surgery within the last 28 days.
  • Patients with primary central nervous system (CNS) tumors and/or metastases.
  • History of severe, acute or chronic heart diseases.
  • History of severe, acute or chronic renal diseases or inadequate renal function.
  • Any of the following within 6 months prior to study enrollment: pulmonary embolism, infectious or inflammatory bowel disease, diverticulitis, intestinal obstruction or perforation and gastrointestinal hemorrhage.
  • Inadequate hematological or liver function.
  • Non-resolution of any prior treatment related toxicity to Grade <2.
  • Prior treatment with any anti-transforming growth factor ? (anti-TGF?) inhibitors.
  • Known allergies to any component of SAR439459 and/or REGN2810.
  • Patients who received prior immunotherapy who developed toxicity leading to a permanent discontinuation of immunotherapy.
  • Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
  • Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of SAR439459 and/or REGN2810 (occasional use of inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed).
  • History of pneumonitis or bowel perforation.
  • Patients with underlying cancer predisposition syndromes. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
  • Gender

    All

    Ages

    18 Years and older

    Accepts Healthy Volunteers

    No

    Study Locations and Contact Information (3)

    Study Location Distance Name Phone Email
    Investigational Site Number 8400001 - Boston, Massachusetts 2.8 miles None None None
    Investigational Site Number 8400006 - Nashville, Tennessee 942.8 miles None None None
    Investigational Site Number 8400003 - Dallas, Texas 1,546.2 miles None None None

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