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

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ClinicalTrials.gov Identifier: NCT03424603
Recruitment Status : Recruiting
First Posted : February 7, 2018
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Sutro Biopharma, Inc.

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

Condition or disease Intervention/treatment Phase
B-cell Lymphoma Non Hodgkin Lymphoma Multiple Myeloma Follicular Lymphoma Mantle Cell Lymphoma Diffuse Large B Cell Lymphoma Indolent Lymphoma B Cells--Tumors Drug: STRO-001 Phase 1

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).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 22, 2018
Estimated Primary Completion Date : November 2021
Estimated Study Completion Date : November 2023


Arm Intervention/treatment
Experimental: STRO-001
intravenous
Drug: STRO-001
intravenous antibody drug conjugate




Primary Outcome Measures :
  1. Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001) [ Time Frame: 18 months ]
    Incidence of adverse events (AEs) observed across STRO-001 dose levels

  2. Part 1: Define the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of STRO-001 [ Time Frame: 18 months ]
    Frequency of dose-limiting toxicity and exposure across STRO-001 dose levels

  3. Part 2: Evaluate preliminary anti-tumor activity (multiple myeloma patients) [ Time Frame: 24 months ]
    Objective response rates per International Myeloma Working Group (IMWG) criteria for response assessment

  4. Part 2: Evaluate preliminary anti-tumor activity (NHL patients) [ Time Frame: 24 months ]
    Objective response rates per the Lugano classification for response assessment


Secondary Outcome Measures :
  1. Part 1: Characterize the pharmacokinetics (PK) of STRO-001 by measuring the maximum plasma concentration (Cmax) [ Time Frame: 18 months ]
    Measurement of maximum plasma concentration after the administration of STRO-001

  2. Part 1: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001 [ Time Frame: 18 months ]
    Measurement of terminal half-life of STRO-001 after the administration of STRO-001

  3. 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 ]
    Measurement of AUC to infinity (AUCinf)

  4. Part 1: Characterize the PK of STRO-001 by measuring the clearance (CL) [ Time Frame: 18 months ]
    Measurement of total body clearance

  5. Part 1: Characterize the PK of STRO-001 by measuring the the steady state volume of distribution (Vss) [ Time Frame: 18 months ]
    Measurement of steady state volume of distribution

  6. Part 1: Assess the immunogenic potential of STRO-001 [ Time Frame: 18 months ]
    Evaluation and quantitation of circulating anti-drug antibodies (ADAs) over time

  7. Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001) [ Time Frame: 24 months ]
    Number of patients with abnormal laboratory values and/or adverse events related to STRO-001 treatment

  8. 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 ]
    Each cohort will be analyzed independently

  9. 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 ]
    Each cohort will be analyzed independently

  10. Part 2: Characterize the PK of STRO-001 by measuring the maximum plasma concentration (Cmax) [ Time Frame: 24 months ]
    Measurement of maximum plasma concentration after the administration of STRO-001

  11. Part 2: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001 [ Time Frame: 24 months ]
    Measurement of terminal half-life of STRO-001 after the administration of STRO-001

  12. Part 2: Characterize the PK of STRO-001 by measuring the area under the plasma concentration versus time curve (AUC) [ Time Frame: 24 months ]
    Measurement of AUC to infinity (AUC inf)

  13. Part 2: Characterize the PK of STRO-001 by measuring the clearance (CL) [ Time Frame: 24 months ]
    Measurement of total body clearance


Other Outcome Measures:
  1. Part 1: Preliminary assessment of the anti-tumor activity of STRO-001 (multiple myeloma patients) [ Time Frame: 18 months ]
    Objective response rates per IMWG criteria for response assessment

  2. Part 1: Preliminary assessment of the anti-tumor activity of STRO-001 (NHL) [ Time Frame: 18 months ]
    Objective response rates per the Lugano classification for response assessment (NHL patients)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03424603


Contacts
Contact: Shannon Matheny, PhD 1-650-676-4610 STRO-001ClinDev@sutrobio.com

Locations
United States, California
City of Hope Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Amrita Krishnan, M.D.    626-256-4673    akrishnan@coh.org   
Univeristy of California San Francisco HDF Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143
Contact: Danielle Kilayko    415-502-3549    Danielle.Kilayko@ucsf.edu   
Principal Investigator: Nina Shah, MD         
United States, Colorado
Rocky Mountain Cancer Center Recruiting
Aurora, Colorado, United States, 80012
Contact: Mary Catherine Jerome    281-541-9285    MaryCatherine.Jerome@McKesson.com   
Principal Investigator: John Burke, MD         
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: John Bourgeois    404-778-1802 ext 30577    John.bourgeois@emoryhealthcare.org   
Principal Investigator: Jonathan Kaufman, MD         
United States, Texas
Texas Oncology Recruiting
Austin, Texas, United States, 78705
Contact: Mary Catherine Jerome    281-541-9285    MaryCatherine.Jerome@McKesson.com   
Principal Investigator: Jason Melear, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Karin Choquette, MSN/RN    571-389-0873    Karin.Choquette@USOncology.com   
Principal Investigator: Alexander Spira, MD, PhD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: General Cancer Center Info    866-680-0505 ext 8900    cccto@mcw.edu   
Principal Investigator: Nirav Shah, MD         
Sponsors and Collaborators
Sutro Biopharma, Inc.
Investigators
Study Director: Arturo Molina, MD Sutro Biopharma

Additional Information:
Responsible Party: Sutro Biopharma, Inc.
ClinicalTrials.gov Identifier: NCT03424603     History of Changes
Other Study ID Numbers: STRO-001-BCM1
First Posted: February 7, 2018    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Multiple Myeloma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Antibodies
Immunoglobulins
Immunologic Factors
Physiological Effects of Drugs