Clinical Trial - NCT03192345

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

Recruiting

Sponsor: Sanofi

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03192345

Protocol Info

Short Description: Phase 1/1b SAR439459 +/- REGN2810 in Solid Tumors
Long Description: A Phase 1/1b first-in-human dose escalation and expansion study for the evaluation of safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of SAR439459 administered intravenously as monotherapy and in combination with REGN2810 in adult patients with advanced solid tumors
MGH Status: Open
Sponsor: Sanofi
Disease Program: Phase I

Next Steps


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Purpose

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 cemiplimab combination therapy) - To determine the MTD and/or MAD of SAR439459 administered intravenously in combination with cemiplimab 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 cemiplimab combination therapy) - To determine the objective response rate (ORR) of SAR439459 in combination with cemiplimab in adult patients with selected advanced solid tumors by evaluation of antitumor response according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). Secondary Objectives: - Pharmacokinetic (PK) profile SAR439459 monotherapy and combined with cemiplimab, PK profile of cemiplimab combined with SAR439459. - Immunogenicity of SAR439459 monotherapy and combined with cemiplimab. Dose escalation (Part 1) - Overall safety/tolerability profile of SAR439459 monotherapy and combined with cemiplimab. - Preliminary recommended phase 2 dose (pRP2D) of SAR439459 as monotherapy or combined with cemiplimab. Dose expansion (Part 2) - Progression free survival (PFS), time to progression (TTP), ORR, and safety of SAR439459 as monotherapy and PFS, TTP and safety in combination with cemiplimab in adult patients with advanced melanoma who have failed a prior therapy based on anti-PD-1 or anti-PD-L1 and patients with mesenchymal Colorectal cancer. - PFS, duration of response (DOR) and safety in adult patients with metastatic urothelial cancer. - To confirm the optimal dose of SAR439459 administered in combination with cemiplimab.
Condition Title Intervention Phase
Malignant Solid Tumor SAR439459 Cemiplimab REGN2810 Phase 1
Study Type Interventional
Official Title A Phase 1/1b First-in-human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR439459 Administered Intravenously as Monotherapy and in Combination With Cemiplimab in Adult Patients With Advanced Solid Tumors

Primary Outcome Measures

Incidence of Dose Limiting Toxicities (DLTs) [Time Frame: Through the end of two cycles, total duration up to 6 weeks (for Part 1A each cycle is 2 weeks; for Part 1B each cycle is 2 or 3 weeks)] [Designated as safety issue: ]

Objective Response Rate (ORR) for Part 2B [Time Frame: Continuous throughout study assessment (up to approximately 1 year)] [Designated as safety issue: ]


Secondary Outcome Measures

Overall safety profile [Time Frame: Continuous throughout study assessment (up to approximately 1 year)] [Designated as safety issue: ]

Progression free survival (PFS) [Time Frame: Continuous throughout study assessment (up to approximately 1 year)] [Designated as safety issue: ]

Time to progression (TTP) [Time Frame: Continuous throughout study assessment (up to approximately 1 year)] [Designated as safety issue: ]

Objective Response Rate (ORR) Part 2A [Time Frame: Continuous throughout study assessment (up to approximately 1 year)] [Designated as safety issue: ]

Duration of response Part 2B (urothelial cancer cohort only) [Time Frame: Continuous throughout study assessment (up to approximately 1 year)] [Designated as safety issue: ]

Immunogenicity evaluation [Time Frame: Up to approximately 1 year] [Designated as safety issue: ]

Cmax for SAR439459 and for cemiplimab [Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22] [Designated as safety issue: ]

AUC for SAR439459 [Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22] [Designated as safety issue: ]

AUC0-tau for SAR439459 and for cemiplimab [Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22] [Designated as safety issue: ]

t1/2z for SAR439459 [Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22] [Designated as safety issue: ]

CL for SAR439459 [Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22] [Designated as safety issue: ]

Vss for SAR439459 [Time Frame: Cycle 1, Day 1 to Day 15 or to Day 22] [Designated as safety issue: ]

Estimated Enrollment: 225
Study Start Date: June 2017
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: October 2020
Arms Assigned Interventions

Experimental:Dose Escalation SAR439459 monotherapy

SAR439459 administered intravenously every 2 weeks in a 14-day cycle with escalating doses
Biological:SAR439459
Pharmaceutical form: powder for solution for infusion Route of administration: intravenous infusion

Experimental:Dose Expansion SAR439459 monotherapy

SAR439459 administered intravenously every 2 weeks in a 14-day cycle with the previously determined recommended dose

Experimental:Dose Escalation SAR439459 + cemiplimab combination

SAR439459 + cemiplimab combination administered intravenously every 2 weeks in a 14-day cycle or every 3 weeks in a 21-day cycle with escalating SAR439459 doses and cemiplimab at a standard dose
Drug:Cemiplimab REGN2810
Pharmaceutical form: solution Route of administration: intravenous infusion

Experimental:Dose Expansion SAR439459 + cemiplimab combination

SAR439459 + cemiplimab combination administered intravenously every 3 weeks in a 21-day cycle with a previously determined SAR439459 dose and cemiplimab at a standard dose

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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 or colorectal adenocarcinoma or patients with urothelial cancer.
  • Melanoma patients must have failed one prior therapy based on anti-PD-1 or anti-PD-L1.
  • Patients with colorectal cancer must have progressed after last line of therapy.
  • Patients with urothelial cancer must have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Patients must not have received >2 prior lines therapy. Patients must not have received prior treatment with anti-PD1 or anti-PDL1.
  • Patients with histologically confirmed, advanced unresectable or metastatic melanoma, colorectal cancer or metastatic urothelial cancer whom in the opinion of the Investigator does not have a suitable alternative therapy.

Dose expansion parts 2A and 2B

  • At least 1 measurable lesion by RECIST v1.1.

All cohorts

  • 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 >38.1ºC), 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, 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 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 CNS metastases of non-CNS primary tumors that are untreated.
  • History of severe, congestive heart failure, myocardial infarction with reduced ejection fraction, symptomatic coronary artery disease, documented uncontrolled hypertension, major clinically significant Electrocardiography (ECG) and echocardiogram abnormalities, significant ventricular arrhythmias, significant valvular heart disease (including valve replacement), vascular malformation, aneurysm, significant pulmonary conditions such as idiopathic pulmonary hypertension, uncontrolled chronic lung disease.
  • History of severe, acute or chronic renal diseases.
  • Any of the following within 6 months prior to study enrollment: pulmonary embolism, deep vein thrombosis, active uncontrolled bleeding, infectious or inflammatory bowel disease, diverticulitis, intestinal obstruction or perforation and gastrointestinal hemorrhage.
  • Inadequate hematological, renal or liver function.
  • Non-resolution of any prior treatment related toxicity to Grade <2.
  • Prior treatment with any anti-transforming growth factor β (anti-TGFβ) inhibitors.
  • Known allergies to any component of SAR439459 and/or cemiplimab.
  • Patients with uveal melanoma and patients with prior or ongoing uveitis.
  • Patients who received prior immunotherapy who developed toxicity leading to a permanent discontinuation of immunotherapy.
  • Ongoing or recent (within 5 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 cemiplimab (occasional use of inhaled, intraocular, nasal or topical steroids for symptomatic relief allowed).
  • History of interstitial lung disease or active non-infectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management.
  • Patients with underlying cancer predisposition syndromes.
  • Receipt of a live vaccine within 30 days of planned start of study medication.
  • Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior the first dose of SAR439459.
  • Prothrombin time (PT) or international normalized ratio (INR) > 1.5 × upper limit of normal (ULN).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03192345

Locations

  • United States, California
    • Investigational Site Number 8400007 Duarte, California, United States, 91010
  • United States, Kansas
    • Investigational Site Number 8400004 Fairway, Kansas, United States, 66205
  • United States, Massachusetts
    • Investigational Site Number 8400001 Boston, Massachusetts, United States, 02114
    • Investigational Site Number 8400101 Boston, Massachusetts, United States, 02115
  • United States, Tennessee
    • Investigational Site Number 8400006 Nashville, Tennessee, United States, 37203
  • United States, Texas
    • Investigational Site Number 8400003 Dallas, Texas, United States, 75230
  • Netherlands,
    • Investigational Site Number 5280001 Rotterdam, , Netherlands, 3015 GD

Sponsors and Collaborators

Sanofi

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03192345
Other Study ID Numbers: 2018-001113-32
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Cemiplimab

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on July 18, 2019