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

Multiple Myeloma Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03424603
• Other study ID #: STRO-001-BCM1
• Status: Completed
• Phase: Phase 1
• Start date: February 22, 2018
• Est. completion date: March 15, 2024

Study information

• Verified date: June 2024
• Source: Sutro Biopharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: March 15, 2024
• Est. primary completion date: February 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• STRO-001
intravenous antibody drug conjugate

Locations

Country	Name	City	State
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	Rocky Mountain Cancer Center	Aurora	Colorado
United States	Texas Oncology	Austin	Texas
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	City of Hope Medical Center	Duarte	California
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	University of Kansas Cancer Center	Fairway	Kansas
United States	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	West Virginia University	Morgantown	West Virginia
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	UT Health San Antonio	San Antonio	Texas
United States	Univeristy of California San Francisco HDF Comprehensive Cancer Center	San Francisco	California
United States	Arizona Oncology Associates, PC--HOPE Division	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Sutro Biopharma, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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
Primary	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
Primary	Part 2: Evaluate preliminary anti-tumor activity (NHL patients)	Objective response rates per the Lugano classification for response assessment	24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1: Characterize the PK of STRO-001 by measuring the clearance (CL)	Measurement of total body clearance	18 months
Secondary	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
Secondary	Part 1: Assess the immunogenic potential of STRO-001	Evaluation and quantitation of circulating anti-drug antibodies (ADAs) over time	18 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 2: Characterize the PK of STRO-001 by measuring the clearance (CL)	Measurement of total body clearance	24 months

External Links

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