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A Study of SAR428926 in Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02575781
Recruitment Status : Completed
First Posted : October 15, 2015
Last Update Posted : August 22, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE October 8, 2015
First Posted Date  ICMJE October 15, 2015
Last Update Posted Date August 22, 2018
Actual Study Start Date  ICMJE October 5, 2015
Actual Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
  • Number of patients with dose limiting adverse events (Escalation cohort) [ Time Frame: 4 weeks ]
  • Number of patients with corneal adverse events impacting study treatment (Escalation cohort) [ Time Frame: 8 weeks ]
  • Assessment of overall response rate using standard imaging and RECIST v1.1 criteria (Expansion cohort) [ Time Frame: Tumor assessment every 2 months until disease progression or up to 36 months, whichever came first ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
  • Number of patients with dose limiting adverse events (Escalation cohort) [ Time Frame: 4 weeks ]
  • Number of patients with corneal adverse events impacting study treatment (Escalation cohort) [ Time Frame: 8 weeks ]
  • Preliminary assessment of overall response rate using standard imaging and RECIST v1.1 criteria (Expansion cohort) [ Time Frame: Tumor assessment every 2 months until disease progression or up to 30 months, whichever came first ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
  • Number of treatment emergent adverse events [ Time Frame: Up to 3 years ]
  • Assessment of PK parameter: maximum concentration (Cmax) [ Time Frame: 2 months ]
  • Assessment of PK parameter: time to reach maximum concentration (tmax) [ Time Frame: 2 months ]
  • Assessment of PK parameter: trough plasma concentration (Ctrough) [ Time Frame: Every 2 weeks until approximately 14 weeks ]
  • Assessment of PK parameter: area under the plasma concentration curve versus time curve between 1 and 14 days (AUC0-14 day) [ Time Frame: 2 months ]
  • Assessment of PK parameter: mean systemic clearance (CL) [ Time Frame: 2 months ]
  • Assessment of PK parameter: clearance at steady state (CLss) [ Time Frame: 2 months ]
  • Assessment of PK parameter: accumulation ratio on AUC0-14 [ Time Frame: 2 months ]
  • Assessment of PK parameter: accumulation ratio on Cmax [ Time Frame: 2 months ]
  • Preliminary tumor response by RECIST v1.1 (Escalation) [ Time Frame: 2 months ]
  • Number of corneal events according to the presence or not of preventive measures [ Time Frame: 12 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
  • Number of treatment emergent adverse events [ Time Frame: Up to 2.5 years ]
  • Assessment of PK parameter: maximum concentration (Cmax) [ Time Frame: 2 months ]
  • Assessment of PK parameter: time to reach maximum concentration (tmax) [ Time Frame: 2 months ]
  • Assessment of PK parameter: trough plasma concentration (Ctrough) [ Time Frame: Every 2 weeks until approximately 14 weeks ]
  • Assessment of PK parameter: area under the plasma concentration curve versus time curve between 1 and 14 days (AUC0-14 day) [ Time Frame: 2 months ]
  • Assessment of PK parameter: mean systemic clearance (CL) [ Time Frame: 2 months ]
  • Assessment of PK parameter: clearance at steady state (CLss) [ Time Frame: 2 months ]
  • Assessment of PK parameter: accumulation ratio on AUC0-14 [ Time Frame: 2 months ]
  • Assessment of PK parameter: accumulation ratio on Cmax [ Time Frame: 2 months ]
  • Preliminary tumor response by RECIST v1.1 (Escalation) [ Time Frame: 2 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of SAR428926 in Patients With Advanced Solid Tumors
Official Title  ICMJE A First-in-human Phase 1 Dose Escalation Study of SAR428926 in Patients With Advanced Solid Tumors
Brief Summary

Primary Objectives:

To determine the maximum tolerated dose (MTD) of SAR428926 when administered as a single agent in patients with advanced solid tumors.

To evaluate the anti-tumor response of SAR428926 when administered as a single agent in patients with advanced triple negative breast cancer (TNBC) positive for the protein targeted by SAR428926 To assess the preliminary anti-tumor response of SAR428926 when administered as a single agent in patients with advanced solid tumors positive for the protein targeted by SAR428926

Secondary Objectives:

To determine the overall safety profile of SAR428926 as a single agent. To characterize the pharmacokinetics (PK) profile of SAR428926 and its metabolites.

To identify the recommended Phase 2 dose (RP2D) of SAR428926 as a single agent. To evaluate the immunogenicity of SAR428926. To assess the tumor response and duration of tumor response in all treated patients.

To evaluate the benefit of primary prophylaxis on the occurrence of corneal (keratopathy/keratitis) toxicity (Expansion cohorts).

Detailed Description The study duration for an individual patient will include a screening period for inclusion of up to 28 days, a treatment period, an end-of-treatment (EOT) visit around 30 days following the last administration of SAR428926, and at least one follow-up visit around 30 days after the EOT visit. The treatment period may continue until disease progression, intolerable toxicity, or investigator, Sponsor, or patient decision to discontinue therapy. Patients who discontinue treatment for reasons other than progression of disease will be followed every 3 months until progression, initiation of subsequent therapy, or until the primary analysis cutoff date, whichever comes first.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasm Malignant
Intervention  ICMJE Drug: SAR428926
Pharmaceutical form:concentrate for solution for infusion Route of administration: intravenous
Study Arms  ICMJE
  • Experimental: SAR428926-Escalating cohort
    SAR428926 will be administered intravenously up to disease progression or dose limiting toxicities
    Intervention: Drug: SAR428926
  • Experimental: SAR428926 in triple negative breast cancer-Expansion Cohort 1
    SAR428926 will be administered intravenously at maximum tolerated dose (MTD) up to disease progression or unacceptable toxicity
    Intervention: Drug: SAR428926
  • Experimental: SAR428926 in solid tumors-Expansion Cohort 2
    SAR428926 will be administered intravenously at the MTD up to disease progression or unacceptable toxicity
    Intervention: Drug: SAR428926
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 21, 2018)
34
Original Estimated Enrollment  ICMJE
 (submitted: October 12, 2015)
91
Actual Study Completion Date  ICMJE June 2018
Actual Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria :

  • Patients with advanced solid tumor with no standard alternative treatment.
  • Availability of archived tumor tissue for SAR428926 targeted antigen testing.
  • For participants in the Escalation Phase: human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC), gastric cancer, colorectal cancer (CRC), ovarian cancer, prostate cancer and non small-cell lung cancer (NSCLC).
  • For participants in the Expansion Phase: patients with TNBC, prostate cancer, CRC, ovarian cancer or NSCLC and positive SAR428926 targeted antigen.
  • At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and one lesion amenable to biopsy in expansion cohort only (except for NSCLC patients).

Exclusion criteria:

  • Age less than 18 years old.
  • Eastern Cooperative Oncology Group (ECOG) performance status more than 1.
  • New or progressing brain metastases.
  • Concurrent treatment with any other anticancer therapy or inadequate wash-out period for prior anticancer therapies, including other experimental anticancer treatment, before first administration of SAR428926, or non resolution of toxicities induced by these anticancer therapies.
  • Women of reproductive potential and male subjects with female partners of childbearing potential who are not willing to avoid pregnancy.
  • Pregnancy or breast feeding.
  • Prior maytansinoid treatments (DM1 or DM4 antibody drug conjugates [ADCs]).
  • Unwillingness and inability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
  • Significant concomitant illness, including psychiatric condition that, in the opinion of the Investigator or Sponsor, would adversely affect the patient's participation in the study.
  • Any surgery within the preceding 3 weeks.
  • Known human immunodeficiency virus (HIV) infection or active hepatitis B or C viral infection.
  • Poor bone marrow reserve.
  • Poor kidney and liver function.
  • Previous history of chronic corneal diseases (even if asymptomatic) or unresolved acute non-recurrent corneal conditions. Patients wearing contact lenses who are not willing to stop wearing them for the duration of the study.
  • Unresolved signs and symptoms of peripheral neuropathy; Grade 1 is acceptable.
  • Abnormal cardiac function defined by a left ventricular ejection fraction (LVEF) <50%.
  • Known intolerance to infused protein products including other monoclonal antibodies and ADCs.
  • Medical conditions requiring concomitant administration of medications with narrow therapeutic window, metabolized by CYPs and which a dose reduction cannot be considered.
  • Medical conditions requiring concomitant administration of strong CYP3A inhibitors, unless it can be discontinued at least two weeks before first administration of SAR428926.
  • Other prior neoplasm.
  • Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid as per package insert of each drug, including the following: increase intraocular pressure, prior or current glaucoma, narrow-angle glaucoma, ongoing eye infection, uncontrolled hypertension, known/suspected allergy to constituents of the preparation (such as sodium bisulfite).

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark,   France,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02575781
Other Study ID Numbers  ICMJE TED14147
2015-001441-92 ( EudraCT Number )
U1111-1168-4706 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Sanofi
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Sanofi
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP