Clinical Trials /

Evaluation of SAR408701 in Patients With Advanced Solid Tumors

NCT02187848

Description:

Primary Objectives: - To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 2 weeks (with and without a loading dose at Cycle 1) to patients with advanced solid tumors (Main Escalation and Loading Dose Escalation Q2W). - To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 3 weeks to patients with advanced solid tumors (Escalation Q3W Cycle). - To assess efficacy according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) (Expansion Phase) when SAR408701 is administered once every 2 weeks with or without a loading dose at Cycle 1. Secondary Objectives: - To characterize the overall safety profile of SAR408701. - To characterize the pharmacokinetic (PK) profile of SAR408701 and of its potential circulating derivatives. - To identify the recommended phase 2 dose (RP2D) of SAR408701. - To assess the potential immunogenicity of SAR408701.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of SAR408701 in Patients With Advanced Solid Tumors
  • Official Title: A First-in-Human Study for the Evaluation of the Safety, Pharmacokinetics and Antitumor Activity of SAR408701 in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: TED13751
  • SECONDARY ID: 2014-001130-29
  • NCT ID: NCT02187848

Conditions

  • Neoplasm Malignant

Interventions

DrugSynonymsArms
SAR408701SAR408701 Main Dose Escalation Cohort

Purpose

Primary Objectives: - To determine the maximum tolerated dose (MTD) of SAR408701 administered as monotherapy, once every 2 weeks (with and without a loading dose at Cycle 1) to patients with advanced solid tumors (Escalation Phase). - To assess efficacy according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) (Expansion Phase) when SAR408701 is administered once every 2 weeks with or without a loading dose at Cycle 1. Secondary Objectives: - To characterize the overall safety profile of SAR408701. - To characterize the pharmacokinetic (PK) profile of SAR408701 and of its potential circulating derivatives. - To identify the recommended phase 2 dose (RP2D) of SAR408701. - To assess the potential immunogenicity of SAR408701.

Detailed Description

      The study duration for an individual patient will start from the signature of the informed
      consent, 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 visit around 30
      days following the last administration of study drug, and at least one follow-up visit after
      the end-of-treatment visit. Additional follow-up visits may be required until resolution or
      stabilization of adverse events (at least 30 days). Treatment may continue until precluded by
      toxicity, progression, or upon patient's request. If the patient stops study treatment for
      reason other than disease progression, follow-up visit will be performed every 3 months until
      disease progression or initiation of another anti-tumor treatment or death, whichever comes
      first.
    

Trial Arms

NameTypeDescriptionInterventions
SAR408701 Main Dose Escalation CohortExperimentalDose escalation administered intravenously, once every two weeks
  • SAR408701
SAR408701 Expansion Cohort colorectal cancer (CRC)ExperimentalAdministered intravenously at the maximum tolerated dose (MTD), once every 2 weeks, to patients with colorectal cancer
  • SAR408701
SAR408701 Expansion Cohort non-squamous NSCLCExperimentalAdministered intravenously at the MTD, once every 2 weeks, to patients with carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expressing non-squamous non-small cell lung cancer (NSCLC) of at least 50% of tumor cells at or above 2+ intensity
  • SAR408701
SAR408701 Expansion Cohort gastric adenocarcinomaExperimentalAdministered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing gastric adenocarcinoma
  • SAR408701
SAR408701 Loading Dose Escalation cohorts (Escalation bis)ExperimentalLoading dose escalation administered intravenously at first cycle, followed by MTD, once every 2 weeks
  • SAR408701
SAR408701 Expansion Cohort non-squamous NSCLC (Lung bis)ExperimentalAdministered intravenously at the MTD, once every 2 weeks, to patients with carcinoembryonic CEACAM5 expressing non-squamous NSCLC of at least 1% but below 50% of tumor cells at or above 2+ intensity
  • SAR408701
SAR408701 Expansion Cohort colorectal cancer (CRC-L)ExperimentalLoading dose of determined MTD-L administered intravenously at first cycle, followed by MTD, once every 2 weeks
  • SAR408701
SAR408701 Expansion Cohort small cell lung cancer (SCLC)ExperimentalAdministered intravenously at the MTD, once every 2 weeks, to patients with CEACAM5 expressing SCLC
  • SAR408701

Eligibility Criteria

        Inclusion criteria:

          -  Locally advanced or metastatic solid malignant tumor disease for which no standard
             alternative therapy is available.

          -  Availability of archived tumor tissue for carcinoembryonic antigen-related cell
             adhesion molecule 5 (CEACAM5 or CEA) testing.

          -  For participants in the Main Escalation Phase and in the Loading dose Escalation bis
             cohorts : patients with tumors expressing or likely to be expressing CEACAM5 which
             includes colorectal cancer (CRC), non-squamous non-small cell lung cancer (NSCLC),
             gastric adenocarcinoma, squamous cell carcinoma of the cervix, pancreas
             adenocarcinoma, bladder transitional cell carcinoma, cholangiocarcinoma, epithelial
             ovarian cancer and endometrial adenocarcinoma are favored, or if carcinoembryonic
             antigen (CEA) plasma levels >5 ng/mL.

          -  For participants to the Expansion Phase cohorts: patients with CRC or with CEACAM5
             positive non-squamous NSCLC, small cell lung cancer (SCLC) or gastric carcinoma
             (including esophago-gastric junction adenocarcinoma of the Siewert types II and III).

          -  At least one measurable lesion by RECIST v1.1 in the Expansion Phase only.

          -  At least one lesion amenable to biopsy (Expansion cohort - CRC and gastric cancer
             only). Patient must consent to a baseline biopsy for retrospective confirmation of
             tumor CEACAM5 expression, except if NSCLC or SCLC without lesion amenable to biopsy.

          -  Signed informed consent.

        Exclusion criteria:

          -  Aged less than 18 years.

          -  Eastern Cooperative Oncology Group (ECOG) performance status more than 1.

          -  New or progressing brain involvement.

          -  Concurrent treatment with any other anticancer therapy or inadequate wash-out period
             for prior anticancer therapies before first administration of SAR408701, or
             non-resolution of toxicities induced by these anticancer therapies.

          -  Female or male patients with reproductive potential who do not agree to use an
             accepted effective method of contraception during the study treatment period and for
             at least 3 months following completion of study treatment.

          -  Pregnancy or breast-feeding.

          -  Participation to any clinical research study evaluating another investigational drug
             or therapy within 3 weeks of initiation of study regimen.

          -  Prior therapy targeting CEACAM5.

          -  Prior maytansinoid treatments (DM1 or DM4 antibody drug conjugates).

          -  Poor bone marrow reserve resulting in low blood cell counts.

          -  Poor kidney and liver functions.

          -  Any of the following within 6 months prior to study enrolment: infectious or
             inflammatory bowel disease, diverticulitis, gastrointestinal perforation, intestinal
             obstruction, and gastrointestinal hemorrhage. Patients with malabsorption syndrome are
             excluded.

          -  Previous history and or unresolved corneal disorders. The use of contact lenses is not
             permitted.

          -  Unresolved signs and symptoms of neuropathy; Grade 1 is acceptable if prior neurotoxic
             drugs such as cisplatin or taxanes.

          -  Abnormal cardiac function defined by a left ventricular ejection fraction (LVEF) of
             <50%.

          -  Cardiac conduction defects, or any other clinically significant arrhythmias.

          -  Known intolerance to infused protein products.

          -  Medical conditions requiring concomitant administration of medications with narrow
             therapeutic window, metabolized by cytochrome P450 (CYPs) enzymes 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 1st administration of SAR408701.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of dose limiting adverse events
Time Frame:4 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of treatment emergent adverse events
Time Frame:Up to 4 years
Safety Issue:
Description:
Measure:Maximum concentration (Cmax)
Time Frame:2 months
Safety Issue:
Description:
Measure:Time to reach maximum concentration (tmax)
Time Frame:2 months
Safety Issue:
Description:
Measure:Trough plasma concentrations (Ctrough)
Time Frame:Intensive testing within first 2 months, then every 2 weeks
Safety Issue:
Description:
Measure:Area under the plasma concentration versus time curve between 0 and 14 days (AUC0-14day)
Time Frame:2 months
Safety Issue:
Description:
Measure:Mean systemic clearance (CL)
Time Frame:2 months
Safety Issue:
Description:
Measure:Clearance at steady state (CLss)
Time Frame:2 months
Safety Issue:
Description:
Measure:Accumulation ratio (Rac) on AUC0-14day and Cmax
Time Frame:2 months
Safety Issue:
Description:
Measure:Detection of the development of anti-SAR408701 antibody
Time Frame:Every 2 weeks for 6 weeks, then every 4 weeks until end of treatment
Safety Issue:
Description:
Measure:Duration of response
Time Frame:Up to 40 months - assessment every 8 weeks
Safety Issue:
Description:
Measure:Time to Progression
Time Frame:Up to 40 months - assessment every 8 weeks
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sanofi

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