Clinical Trials /

Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate in Ovarian & Endometrial Cancers

NCT03748186

Description:

First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-002 given intravenously every 3 weeks.

Related Conditions:
  • Endometrial Carcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate in Ovarian & Endometrial Cancers
  • Official Title: A Phase 1 Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate (ADC) in Advanced Epithelial Ovarian Cancer and Endometrial Cancers

Clinical Trial IDs

  • ORG STUDY ID: STRO-002-GM1
  • NCT ID: NCT03748186

Conditions

  • Ovarian Cancer
  • Ovarian Carcinoma
  • Ovary Cancer
  • Endometrial Cancer
  • Endometrioid Adenocarcinoma
  • Fallopian Tube Cancer
  • Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
STRO-002STRO-002 treatment

Purpose

First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-002 given intravenously every 3 weeks.

Detailed Description

      This study is a first-in-human Phase 1, open-label, multicenter, dose escalation study with
      dose expansion to identify the maximum tolerated dose (MTD), the recommended phase 2 dose
      (RP2D) and to evaluate the safety, tolerability, and preliminary anti-tumor activity of
      STRO-002 in adult subjects with advanced epithelial ovarian cancer (including fallopian or
      primary peritoneal cancer) and endometrial cancer. Fallopian tube and primary peritoneal
      cancers are treated in the same manner as epithelial ovarian cancers and are thus included in
      this phase 1 study. Subjects eligible for this study exhibit advanced relapsed and/or
      progressive disease. The study will consist of two parts: Part 1, dose escalation, and Part
      2, dose expansion.

      Part 1 (dose escalation) will enroll subjects with relapsed and/or progressive ovarian,
      fallopian tube or primary peritoneal cancer. Part 2 (dose expansion) will enroll subjects
      with relapsed and/or progressive ovarian, fallopian tube or primary peritoneal cancer (Cohort
      A) and subjects with relapsed and/or progressive epithelial endometrial cancer with
      sufficient FolRα expression per IHC as assessed by Sponsor (Cohort B).

      During dose escalation (Part 1), the initial three dose levels will be evaluated with an
      N-of-1 approach followed by a standard 3+3 enrollment for all subsequent dose levels.
      Subjects with endometrial cancer will not be enrolled in the dose escalation part of the
      study. Subjects will be dosed based on adjusted ideal body weight (AIBW). The starting dose
      was determined to be the human equivalent dose (HED) of 1/6 the highest non-severely toxic
      dose (HNSTD) identified in the good laboratory practice (GLP) toxicology study in cynomolgus
      monkeys. Subsequent doses follow a modified Fibonacci sequence for dose escalation, the
      second dose increases by 100% of the initial dose, and thereafter by 80%, then 60%, 50%, 40%,
      30% and then 20% of the preceding doses. The first three dose levels will enroll only 1
      patient unless there is an instance of a treatment-related, clinically relevant Grade 2
      non-hematologic toxicity or a Grade 3 hematologic toxicity of any type is observed during
      Cycle 1 (first 21 days). Any event meeting these criteria will be reviewed and confirmed by
      the Safety Evaluation Team (SET). When these criteria are met then the dose is expanded with
      2 additional subjects and the standard 3+3 trial design is used for all further dose levels.
      If these criteria are not met during the first 3 dose levels, the standard 3 +3 trial design
      will begin with dose level 4.

      The dose escalation phase of the study will be complete when the MTD is determined and the
      RP2D for dose expansion is identified. After determination of the RP2D, endometrial cancer
      subjects (Cohort B) will be enrolled in the dose expansion part of the study and will be
      analyzed for preliminary efficacy independently from the ovarian (including fallopian tube
      and primary peritoneal) cancer cohort (Cohort A).

      In both Part 1 and Part 2 of the study, STRO-002 will be dosed as an intravenous (IV)
      infusion on Day 1 of 21-day cycles. Clinical evaluations and/or laboratory tests will be
      performed weekly for Cycles 1-4, and at the beginning of every cycle starting with Cycle 5 as
      described in the schedule of assessments. Samples for pharmacokinetics (PK) analysis will
      occur at specific times on Days 1, 2, 8, and 15 of Cycles 1 and 2, Days 1, 8 and 15 of Cycles
      3 and 4 and at the end of treatment (EOT) visit. Additional clinical evaluations and lab
      testing may occur at the discretion of the investigator.

      Subjects who receive any dose of STRO-002 will be included in safety analyses. Disease
      evaluations will include peripheral blood analysis and scans as appropriate. Disease status
      will be evaluated per RECIST 1.1 criteria. Samples will be collected to assess the PK and
      immunogenicity of STRO-002. Biomarkers may be assessed from peripheral blood and/or tissue
      samples. Subjects will continue to receive study drug until disease progression, unacceptable
      toxicity, withdrawal of consent, or end of study (study completion).
    

Trial Arms

NameTypeDescriptionInterventions
STRO-002 treatmentExperimentalSTRO-002 at increasing dose levels
  • STRO-002

Eligibility Criteria

        Inclusion Criteria:

          1. Confirmation of diagnosis

          2. Relapsed or relapsed/refractory disease

          3. Age ≥ 18 years

          4. ECOG performance status (0-1)

          5. Life expectancy > 3 months

          6. Adequate bone marrow, liver and renal functions

          7. QTcF <500 msec

          8. Ability to comply with treatment, PK and test schedules

        Exclusion Criteria:

          1. Low grade ovarian carcinoma (Grade 1).

          2. Clear cell, mucinous and sarcomatous ovarian carcinomas.

          3. Prior treatment with a FolRα-targeting ADCs or FolRα-targeting vaccines

          4. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or
             to antibody-related fusion protein treatment

          5. Sensory or motor neuropathy ≥ grade 2

          6. Chronic or ongoing active infectious disease requiring systemic treatment such as, but
             not limited to, chronic renal infection, chronic chest infection with bronchiectasis,
             tuberculosis and active hepatitis C

          7. Ongoing immunosuppressive therapy, including systemic corticosteroids. Note:
             Physiologic replacement and use of topical or inhaled corticosteroids are allowed.

          8. Clinically significant cardiac disease

          9. Clinically significant pre-exisiting ocular disorders

         10. Significant concurrent, uncontrolled medical condition

         11. History or clinical signs of meningeal or active CNS involvement

         12. Known severe chronic obstructive pulmonary disease or asthma

         13. History of significant cerebrovascular disease

         14. Known Human Immunodeficiency Virus seropositivity

         15. Positive serology for hepatitis B defined by a positive test for HBsAg

         16. Concurrent participation in another therapeutic treatment trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002)
Time Frame:18 months
Safety Issue:
Description:Incidence of adverse events (AEs) observed across STRO-002 dose levels

Secondary Outcome Measures

Measure:Part 1: Characterize the pharmacokinetics (PK) of STRO-002 by measuring the maximum plasma concentration (Cmax)
Time Frame:18 months
Safety Issue:
Description:Measurement of maximum plasma concentration after the administration of STRO-002
Measure:Part 1: Characterize the PK of STRO-002 by measuring the half-life (t1/2) of STRO-002
Time Frame:18 months
Safety Issue:
Description:Measurement of terminal half-life of STRO-002 after the administration of STRO-002
Measure:Part 1: Characterize the PK of STRO-002 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf)
Time Frame:18 months
Safety Issue:
Description:Measurement of AUC to infinity (AUCinf)
Measure:Part 1: Characterize the PK of STRO-002 by measuring the clearance (CL)
Time Frame:18 months
Safety Issue:
Description:Measurement of total body clearance
Measure:Part 1: Characterize the PK of STRO-002 by measuring the the steady state volume of distribution (Vss)
Time Frame:18 months
Safety Issue:
Description:Measurement of steady state volume of distribution
Measure:Part 1: Assess the formulation of anti-drug antibodies to STRO-002
Time Frame:18 months
Safety Issue:
Description:Circulating anti-drug antibodies (ADAs) formed to STRO-002
Measure:Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002)
Time Frame:24 months
Safety Issue:
Description:Number of patients with abnormal laboratory values and/or adverse events related to STRO-002 treatment
Measure:Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of duration of response (DOR) in patients treated with STRO-002
Time Frame:24 months
Safety Issue:
Description:Duration of response per RECIST 1.1
Measure:Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-002
Time Frame:24 months
Safety Issue:
Description:Progression-free survival per RECIST 1.1
Measure:Part 2: Evaluate preliminary effect of STRO-002 treatment on CA-125 levels
Time Frame:24 months
Safety Issue:
Description:Response assessment based on the Gynecologic Cancer Intergroup (GCIG) criteria
Measure:Part 2: Characterize the PK of STRO-002 by measuring the maximum plasma concentration (Cmax)
Time Frame:24 months
Safety Issue:
Description:Measurement of maximum plasma concentration (Cmax) after the administration of STRO-002
Measure:Part 2: Characterize the PK of STRO-002 by measuring the area under the plasma concentration versus time curve (AUC)
Time Frame:24 months
Safety Issue:
Description:Measurement of AUC to infinity (AUC inf)
Measure:Part 2: Characterize the PK of STRO-002 by measuring the clearance (CL)
Time Frame:24 months
Safety Issue:
Description:Measurement of total body clearance

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sutro Biopharma, Inc.

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