Clinical Trials /

Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors

NCT03324113

Description:

Primary Objective: - To evaluate tolerability and safety of SAR408701 when administered as a single agent according to the investigational medicinal product (IMP) related dose limiting toxicities (DLTs) to determine the recommended dose (RD) of SAR408701 in Japanese patients with advanced malignant solid tumors. Secondary Objectives: - To characterize the overall safety profile of SAR408701 monotherapy. - To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites. - To evaluate the pharmacodynamic (PDy) effect of SAR408701 on levels of circulating carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for main dose escalation part. - To assess preliminary efficacy according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria and other indicators of antitumor activity. - To assess the potential immunogenicity of SAR408701.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors
  • Official Title: A Phase I Study to Evaluate Safety and Pharmacokinetics of SAR408701 Administered Intravenously as Monotherapy in Japanese Patients With Advanced Malignant Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TCD15054
  • SECONDARY ID: U1111-1191-5464
  • NCT ID: NCT03324113

Conditions

  • Neoplasm Malignant

Interventions

DrugSynonymsArms
SAR408701SAR408701 Monotherapy
dexamethasoneSanteson ophthalmic solutionSAR408701 Monotherapy
naphazolineClearineSAR408701 Monotherapy
diphenhydramineRestamin KowaSAR408701 Monotherapy

Purpose

Primary Objective: - To evaluate tolerability and safety of SAR408701 when administered as a single agent according to the investigational medicinal product (IMP) related dose limiting toxicities (DLTs) to determine the recommended dose (RD) of SAR408701 in Japanese patients with advanced malignant solid tumors. Secondary Objectives: - To characterize the overall safety profile of SAR408701 monotherapy. - To characterize the pharmacokinetic (PK) profile of SAR408701 and its metabolites. - To evaluate the pharmacodynamic (PDy) effect of SAR408701 on levels of circulating carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for main dose escalation part. - To assess preliminary efficacy according to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 criteria and other indicators of antitumor activity. - To assess the potential immunogenicity of SAR408701.

Detailed Description

      The study duration per participant will include a period to assess eligibility (screening
      period) of up to approximately 4 weeks (28 days), a treatment period and an End-of-Treatment
      (EOT) visit around 30 days after the last administration of IMP, and at least one follow-up
      (FU) visit after the EOT visit.
    

Trial Arms

NameTypeDescriptionInterventions
SAR408701 MonotherapyExperimentalSAR408701 Dose escalation administered as a single agent intravenously, on Day 1 and once every two weeks, to patients with malignant solid tumors
  • SAR408701
  • dexamethasone
  • naphazoline
  • diphenhydramine

Eligibility Criteria

        Inclusion criteria:

          -  Locally advanced or metastatic solid malignant tumor disease for which, in the
             judgement of the investigator, no standard alternative therapy is available.

          -  Inclusion is likely to be expressing CEACAM5.

          -  At least 6 x 5 μm slides from formalin-fixed paraffin-embedded (FFPE) archival tissue
             should be available for retrospective central evaluation of CEACAM5 expression.

          -  Patient understands and has signed the Written Informed Consent form and is willing
             and able to comply with the requirements of the trial.

        Exclusion criteria:

          -  Patient less than 20 years old.

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2.

          -  Life expectancy <12 weeks.

          -  Known or symptomatic brain metastasis (other than totally resected or previously
             irradiated and non-progressive/relapsing) or lepto-meningeal carcinomatosis.

          -  Female patients of childbearing potential and male patients with female partners of
             childbearing potential who do not agree to use accepted and effective method of
             contraception during the study treatment period and for 6 months following
             discontinuation of IMP.

          -  Significant concomitant illnesses, including all severe medical conditions which, in
             the opinion of the Investigator or Sponsor, would impair the patient's participation
             in the study or interpretation of the results.

          -  Prior therapy targeting CEACAM5.

          -  Prior maytansinoid treatments (maytansinoid derivative 1 [DM1] or maytansinoid
             derivative 4 [DM4] antibody drug conjugates).

          -  Previous history and or unresolved corneal disorders.

          -  Medical conditions requiring concomitant administration of medications with narrow
             therapeutic window, metabolized by cytochrome P450 (CYP) and for which a dose
             reduction cannot be considered.

          -  Medical conditions requiring concomitant administration of strong CYP3A inhibitor,
             unless it can be discontinued at least 2 weeks before first administration of
             SAR408701.

        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:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:IMP-related dose limiting toxicities (DLT)
Time Frame:4 weeks
Safety Issue:
Description:IMP-related DLTs are defined as adverse events (AE) related to the IMPs in absence of clear evidence to the contrary, after validation by the Study Committee, and if not related to a disease progression, graded using National Cancer Institute common Toxicity Criteria (NCI-CTC) scale v4.03

Secondary Outcome Measures

Measure:Treatment emergent adverse events
Time Frame:Up to an average of 9 months
Safety Issue:
Description:Overall safety profile characterized in terms of the type, frequency, severity, seriousness, and relationship to study therapy of any AEs based on standard and systematic assessment including physical findings, laboratory tests or other investigations
Measure:Maximum observed concentration (Cmax) of SAR408701
Time Frame:Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days)
Safety Issue:
Description:Cmax for SAR408701 will be assessed after single and repeat doses, as relevant
Measure:Cmax of DM4 and Me-DM4
Time Frame:Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days)
Safety Issue:
Description:Cmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant
Measure:Time to reach maximum concentration (Tmax) of SAR408701
Time Frame:Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days)
Safety Issue:
Description:Tmax for SAR408701 will be assessed after single and repeat doses, as relevant
Measure:Tmax of DM4 and Me-DM4
Time Frame:Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days)
Safety Issue:
Description:Tmax for DM4 and Me-DM4 will be assessed after single and repeat doses, as relevant
Measure:Area under the concentration-time curve (AUC) of SAR408701
Time Frame:Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days)
Safety Issue:
Description:AUC of SAR408701 from time zero extrapolated to infinity
Measure:AUC of DM4 and Me-DM4
Time Frame:Main dose-escalation part: Cycle 1 and Cycle 4 (each cycle is 14 days); Dose-escalation bis part with loading dose: Cycle 1 (Cycle 1 is 14 days)
Safety Issue:
Description:AUC of DM4 and Me-DM4 from time zero extrapolated to infinity
Measure:Assessment of PDy effect
Time Frame:Up to an average of 10 months
Safety Issue:
Description:Assessment of plasma CEACAM5 levels in main dose-escalation part
Measure:Assessment of anti-tumor activity
Time Frame:Up to an average of 10 months
Safety Issue:
Description:Assessment of tumor response using standard imaging, as defined by RECIST 1.1 criteria
Measure:Detection of anti-SAR408701 antibody
Time Frame:Up to an average of 10 months
Safety Issue:
Description:Immunogenicity evaluation for anti-SAR408701 antibodies

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

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