Clinical Trials /

Study of STRO-001, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies

NCT03424603

Description:

First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-001 given intravenously every 2 weeks.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of STRO-001, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies
  • Official Title: A Phase 1 Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of STRO-001, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies

Clinical Trial IDs

  • ORG STUDY ID: STRO-001-BCM1
  • NCT ID: NCT03424603

Conditions

  • B-cell Lymphoma
  • Non Hodgkin Lymphoma
  • Multiple Myeloma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Diffuse Large B Cell Lymphoma
  • Indolent Lymphoma
  • B Cells--Tumors

Interventions

DrugSynonymsArms
STRO-001STRO-001

Purpose

First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-001 given intravenously every 2 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 doses
      (RP2D) and to evaluate the safety, tolerability, and preliminary anti-tumor activity of
      STRO-001 in adult subjects with B-cell malignancies (MM and NHL) who are refractory to, or
      intolerant of, all established therapy known to provide clinical benefit for their condition
      (i.e., trial subjects must not be candidates for any regimens known to provide clinical
      benefit). The study will consist of two parts: Part 1, dose escalation, and Part 2, dose
      expansion.

      During Part 1 (dose escalation), an accelerated dose titration design will be applied to
      cohorts A (MM) and B (NHL). Doses will be escalated using an N-of-1 until the first 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 28 days). Any event
      meeting these criteria will be reviewed and confirmed by the Safety Evaluation Team (SET).
      Each dose escalation cohort will be assessed independently. 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 dosing cohorts. The dose escalation (Part 1) phase of the study will be complete
      when the MTD is determined and the recommended dose for Part 2 (dose expansion) is
      identified. The RP2D will be selected based on the safety, tolerability and exposure of
      STRO-001, and will be the end of Part 1 of the study. After determination of the RP2D,
      subjects with MM or NHL will be enrolled into indication specific dose expansion cohorts
      (Part 2). The accelerated dose titration (N-of-1) design with seamless transformation into a
      traditional 3+3 design allows for very low starting doses to be evaluated in fewer patients.

      In both Part 1 and Part 2 of the study, STRO-001 will be dosed as an intravenous (IV)
      infusion on Day 1 and Day 15 in 28-day cycles, until disease progression. Labs will be drawn
      on a weekly basis for Cycles 1-3, and every two weeks starting with Cycle 4. Weekly clinical
      evaluations will be conducted during Cycle 1; thereafter, clinical evaluations will be
      conducted on infusion days (Day 1 and Day 15 of each cycle). Samples for pharmacokinetics
      (PK) analysis will occur at specific times on Days 1, 2, 3, 8, 15, 16, 22, and 29 of
      treatment and at end of treatment visit. Additional clinical evaluations and labs may occur
      at the discretion of the investigator.

      Subjects who receive any dose of STRO-001 will be included in safety analyses. Disease
      evaluations will include peripheral blood analysis, bone marrow assessments and scans as
      appropriate. Disease status will be evaluated per MM-specific or NHL-specific criteria.
      Samples will be collected to assess the PK and immunogenicity of STRO-001. Biomarkers may be
      assessed from bone marrow, 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-001Experimentalintravenous
  • STRO-001

Eligibility Criteria

        Key Inclusion Criteria:

          1. Confirmation of diagnosis

          2. Relapsed or relapsed/refractory disease

          3. Age ≥ 18 years

          4. ECOG performance status (0-2)

          5. Life expectancy > 3 months

          6. Adequate bone marrow and renal functions

          7. QTcF <500 msec

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

          9. NHL only- at least one measurable lesion

        Key Exclusion Criteria:

          1. Active plasma cell leukemia and/or leukemic manifestations of lymphoma

          2. Known amyloidosis (MM patients)

          3. Chronic lymphocytic leukemia and Richter's transformation, and prolymphocytic leukemia
             (NHL subjects)

          4. T-cell malignancy

          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: Subjects
             may be using topical or inhaled corticosteroids.

          8. Clinically significant cardiac disease

          9. Significant concurrent, uncontrolled medical condition

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

         11. Known severe chronic obstructive pulmonary disease or asthma

         12. History of significant cerebrovascular disease

         13. Known Human Immunodeficiency Virus seropositivity

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

         15. Concurrent participation in another therapeutic treatment trial

         16. High screening liver function tests

         17. Prior treatment with CD74 targeting therapy

         18. Patients requiring anti-coagulant therapy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001)
Time Frame:18 months
Safety Issue:
Description:Incidence of adverse events (AEs) observed across STRO-001 dose levels

Secondary Outcome Measures

Measure:Part 1: Characterize the pharmacokinetics (PK) of STRO-001 by measuring the maximum plasma concentration (Cmax)
Time Frame:18 months
Safety Issue:
Description:Measurement of maximum plasma concentration after the administration of STRO-001
Measure:Part 1: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001
Time Frame:18 months
Safety Issue:
Description:Measurement of terminal half-life of STRO-001 after the administration of STRO-001
Measure:Part 1: Characterize the PK of STRO-001 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-001 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-001 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 immunogenic potential of STRO-001
Time Frame:18 months
Safety Issue:
Description:Evaluation and quantitation of circulating anti-drug antibodies (ADAs) over time
Measure:Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001)
Time Frame:24 months
Safety Issue:
Description:Number of patients with abnormal laboratory values and/or adverse events related to STRO-001 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-001
Time Frame:24 months
Safety Issue:
Description:Each cohort will be analyzed independently
Measure:Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-001
Time Frame:24 months
Safety Issue:
Description:Each cohort will be analyzed independently
Measure:Part 2: Characterize the PK of STRO-001 by measuring the maximum plasma concentration (Cmax)
Time Frame:24 months
Safety Issue:
Description:Measurement of maximum plasma concentration after the administration of STRO-001
Measure:Part 2: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001
Time Frame:24 months
Safety Issue:
Description:Measurement of terminal half-life of STRO-001 after the administration of STRO-001
Measure:Part 2: Characterize the PK of STRO-001 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-001 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.

Last Updated

December 10, 2019