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, duration of response (DOR), disease control rate (DCR) and safety in combination with cemiplimab. - 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 1 or 2 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 [Time Frame: Continuous throughout study assessment (up to approximately 1 year)] [Designated as safety issue: ]

Disease Control Rate Part 2B [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: 350
Study Start Date: June 2017
Estimated Study Completion Date: May 2022
Estimated Primary Completion Date: November 2021
Arms Assigned Interventions

Experimental:Dose Escalation SAR439459 monotherapy

SAR439459 administered intravenously every 2 weeks in a 14-day cycle with escalating doses

Experimental:Dose Expansion SAR439459 monotherapy

SAR439459 administered intravenously every 3 weeks in a 21-day cycle with the previously determined recommended doses as the patients will be randomized to 2 different doses

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
Drug:Cemiplimab REGN2810
Pharmaceutical form: solution for infusion 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 previously determined SAR439459 doses and cemiplimab

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 after any prior therapy based on anti-PD-1 or anti-PD-L1 as defined by disease progression within 26 weeks of initiating anti-PD-1 or anti-PD-L1 based therapy without any evidence of a response (primary resistance to anti-PD-1 or anti-PD-L1).
  • • Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy. Patients must be able and willing to provide mandatory tumor biopsies prior to and during study treatment.

Dose expansion (Part 2B)

  • • Patients with disease location amenable to mandatory tumor biopsy at baseline with histologically confirmed advanced unresectable or metastatic melanoma, colorectal adenocarcinoma, urothelial cancer, hepatocellular carcinoma (HCC), or non-small cell lung cancer (NSCLC).
  • • 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 lines of therapy for advanced disease. Patients must not have received prior treatment with anti-PD-1 or anti-PD-L1.
  • • Patients with HCC must have failed after 1 prior therapy based on anti-PD-1 or anti-PD-L1.
  • • Patients with NSCLC must have failed during or after 1 prior therapy based on anti-PD-1 or anti-PD-L1.
  • • Patients with histologically confirmed, advanced unresectable or metastatic melanoma, or colorectal cancer or NSCLC whom in the opinion of the Investigator do 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 or < the country's legal age of majority if the legal age is more than 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 highly 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), HIV serology at screening will be conducted only for patients in German study sites.
  • • Known uncontrolled hepatitis B virus (HBV) infection.
  • • Known untreated current hepatitis C virus (HCV) infection.
  • • 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.
  • • History of 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 ß (anti-TGFß) 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).
  • • Patients accommodated in an institution because of regulatory or legal order; prisoners or patients who are legally institutionalized.

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, North Carolina
    • Investigational Site Number 8400008 Durham, North Carolina, United States, 27710
  • United States, Tennessee
    • Investigational Site Number 8400006 Nashville, Tennessee, United States, 37203
  • United States, Texas
    • Investigational Site Number 8400003 Dallas, Texas, United States, 75230
  • Australia,
    • Investigational Site Number 0360002 Heidelberg West, , Australia, 3081
    • Investigational Site Number 0360001 Melbourne, , Australia, 3000
  • Belgium,
    • Investigational Site Number 0560002 Bruxelles, , Belgium, 1200
    • Investigational Site Number 0560001 Leuven, , Belgium, 3000
  • Canada,
    • Investigational Site Number 1240003 Calgary, , Canada, T2N 4N2
    • Investigational Site Number 1240002 Montreal, , Canada, H3T 1E2
    • Investigational Site Number 1240001 Toronto, , Canada, M5G 2M9
  • Estonia,
    • Investigational Site Number 2330001 Tallinn, , Estonia, 13419
  • France,
    • Investigational Site Number 2500006 Lille, , France, 59037
    • Investigational Site Number 2500002 Marseille, , France, 13385
    • Investigational Site Number 2500003 Nantes, , France, 44093
    • Investigational Site Number 2500005 Nantes, , France, 44093
    • Investigational Site Number 2500004 Paris, , France, 75010
    • Investigational Site Number 2500001 Villejuif, , France, 94805
  • Germany,
    • Investigational Site Number 2760001 Essen, , Germany, 45122
    • Investigational Site Number 2760003 Hannover, , Germany, 30625
  • Italy,
    • Investigational Site Number 3800001 Milano, , Italy, 20133
    • Investigational Site Number 3800002 Milano, , Italy, 20141
    • Investigational Site Number 3800003 Rozzano, , Italy, 20089
  • Korea, Republic of,
    • Investigational Site Number 4100001 Seoul, , Korea, Republic of, 03080
    • Investigational Site Number 4100002 Seoul, , Korea, Republic of, 138-736
  • Netherlands,
    • Investigational Site Number 5280001 Rotterdam, , Netherlands, 3015 GD
    • Investigational Site Number 5280002 Utrecht, , Netherlands, 3584 CX
  • Spain,
    • Investigational Site Number 7240002 Barcelona, , Spain, 08003
    • Investigational Site Number 7240001 Barcelona, , Spain, 08035
    • Investigational Site Number 7240003 Madrid / Madrid, , Spain, 28040
    • Investigational Site Number 7240004 Madrid / Madrid, , Spain, 28050
    • Investigational Site Number 7240005 Pamplona, , Spain, 31008
  • Taiwan,
    • Investigational Site Number 1580003 Kaohsiung, , Taiwan, 807
    • Investigational Site Number 1580002 Tainan, , Taiwan, 704
    • Investigational Site Number 1580001 Taipei 100, , Taiwan,
  • United Kingdom,
    • Investigational Site Number 8260002 Cardiff, , United Kingdom, CF14 2TL
    • Investigational Site Number 8260001 Glasgow, , United Kingdom, G12 0YN

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:

Neoplasms

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 January 14, 2021