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

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

First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-001 given intravenously every 3 weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: Follicular Lymphoma; B-cell Lymphoma; Multiple Myeloma; Mantle Cell Lymphoma; Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Indolent Lymphoma; B Cells--Tumors
• Intervention / Treatment: Drug: STRO-001

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.

The study uses an accelerated dose titration design for dose escalation. Doses will be escalated using an N-of-1 per dosing cohort 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 21 days). Following this a standard 3+3 trial design is used for all further escalation cohorts. Dose escalation is conducted independently for the two dose escalation tumor cohorts (MM and NHL). A recommended STRO-001 dose for expansion will be determined for MM and NHL.

The dose expansion (Part 2) portion of the study will begin when Part 1 is completed. Enrollment in dose expansion will include separate tumor cohorts of MM and NHL.

In both Part 1 and Part 2 of the study, STRO-001 will be dosed as an intravenous (IV) infusion on Day 1 of a 21-day cycle, until disease progression. Labs will be drawn on a weekly basis for Cycles 1-4, and every three weeks starting with Cycle 5. Weekly clinical evaluations will be conducted during the first 4 cycles; thereafter, clinical evaluations will be conducted on infusion days (Day 1 of each cycle). Samples for pharmacokinetics (PK) analysis will occur at specific times on Days 1, 2, and 8 of the first two cycles of treatment, Day 1 of the third cycle 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
• Enrollment (Actual): 70
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates, PC--HOPE Division
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
    • Sacramento, California, United States, 95817
      • UC Davis Comprehensive Cancer Center
    • San Francisco, California, United States, 94143
      • Univeristy of California San Francisco HDF Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Winship Cancer Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Melvin and Bren Simon Cancer Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • West Virginia University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: STRO-001; intravenous	Drug: STRO-001; intravenous antibody drug conjugate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001)	Incidence of adverse events (AEs) observed across STRO-001 dose levels	18 months
Part 1: Define the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of STRO-001	Frequency of dose-limiting toxicity and exposure across STRO-001 dose levels	18 months
Part 2: Evaluate preliminary anti-tumor activity (multiple myeloma patients)	Objective response rates per International Myeloma Working Group (IMWG) criteria for response assessment	24 months
Part 2: Evaluate preliminary anti-tumor activity (NHL patients)	Objective response rates per the Lugano classification for response assessment	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Characterize the pharmacokinetics (PK) of STRO-001 by measuring the maximum plasma concentration (Cmax)	Measurement of maximum plasma concentration after the administration of STRO-001	18 months
Part 1: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001	Measurement of terminal half-life of STRO-001 after the administration of STRO-001	18 months
Part 1: Characterize the PK of STRO-001 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf)	Measurement of AUC to infinity (AUCinf)	18 months
Part 1: Characterize the PK of STRO-001 by measuring the clearance (CL)	Measurement of total body clearance	18 months
Part 1: Characterize the PK of STRO-001 by measuring the the steady state volume of distribution (Vss)	Measurement of steady state volume of distribution	18 months
Part 1: Assess the immunogenic potential of STRO-001	Evaluation and quantitation of circulating anti-drug antibodies (ADAs) over time	18 months
Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001)	Number of patients with abnormal laboratory values and/or adverse events related to STRO-001 treatment	24 months
Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of duration of response (DOR) in patients treated with STRO-001	Each cohort will be analyzed independently	24 months
Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-001	Each cohort will be analyzed independently	24 months
Part 2: Characterize the PK of STRO-001 by measuring the maximum plasma concentration (Cmax)	Measurement of maximum plasma concentration after the administration of STRO-001	24 months
Part 2: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001	Measurement of terminal half-life of STRO-001 after the administration of STRO-001	24 months
Part 2: Characterize the PK of STRO-001 by measuring the area under the plasma concentration versus time curve (AUC)	Measurement of AUC to infinity (AUC inf)	24 months
Part 2: Characterize the PK of STRO-001 by measuring the clearance (CL)	Measurement of total body clearance	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Preliminary assessment of the anti-tumor activity of STRO-001 (multiple myeloma patients)	Objective response rates per IMWG criteria for response assessment	18 months
Part 1: Preliminary assessment of the anti-tumor activity of STRO-001 (NHL)	Objective response rates per the Lugano classification for response assessment (NHL patients)	18 months

Collaborators and Investigators

• Sponsor: Sutro Biopharma, Inc.
• Investigators: Study Director: Arturo Molina, MD, Sutro Biopharma

Publications and helpful links

Helpful Links

• ASH conference, Dec 2017 oral presentation NHL abstract
• ASH conference, Dec 2017 poster presentation multiple myeloma abstract

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2018
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: January 31, 2018
• First Posted (Actual): February 7, 2018

Study Record Updates

• Last Update Posted (Estimate): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Multiple Myeloma; Lymphoma, Mantle-Cell
• Other Study ID Numbers: STRO-001-BCM1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No