Clinical trial NCT03424603: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Lymphoma
Non Hodgkin Lymphoma
Multiple Myeloma
Follicular Lymphoma
Mantle Cell Lymphoma
Diffuse Large B Cell Lymphoma
Indolent Lymphoma
B Cells--Tumors
Lead sponsor: Sutro Biopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2018-02-07
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-001 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 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).

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

Primary outcomes:
measure: Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001)
timeFrame: 18 months
measure: Part 1: Define the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of STRO-001
timeFrame: 18 months
measure: Part 2: Evaluate preliminary anti-tumor activity (multiple myeloma patients)
timeFrame: 24 months
measure: Part 2: Evaluate preliminary anti-tumor activity (NHL patients)
timeFrame: 24 months
Secondary outcomes:
measure: Part 1: Characterize the pharmacokinetics (PK) of STRO-001 by measuring the maximum plasma concentration (Cmax)
timeFrame: 18 months
measure: Part 1: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001
timeFrame: 18 months
measure: Part 1: Characterize the PK of STRO-001 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf)
timeFrame: 18 months
measure: Part 1: Characterize the PK of STRO-001 by measuring the clearance (CL)
timeFrame: 18 months
measure: Part 1: Characterize the PK of STRO-001 by measuring the the steady state volume of distribution (Vss)
timeFrame: 18 months
measure: Part 1: Assess the immunogenic potential of STRO-001
timeFrame: 18 months
measure: Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001)
timeFrame: 24 months
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
timeFrame: 24 months
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
timeFrame: 24 months
measure: Part 2: Characterize the PK of STRO-001 by measuring the maximum plasma concentration (Cmax)
timeFrame: 24 months
measure: Part 2: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001
timeFrame: 24 months
measure: Part 2: Characterize the PK of STRO-001 by measuring the area under the plasma concentration versus time curve (AUC)
timeFrame: 24 months
measure: Part 2: Characterize the PK of STRO-001 by measuring the clearance (CL)
timeFrame: 24 months
Other outcomes:
measure: Part 1: Preliminary assessment of the anti-tumor activity of STRO-001 (multiple myeloma patients)
timeFrame: 18 months
measure: Part 1: Preliminary assessment of the anti-tumor activity of STRO-001 (NHL)
timeFrame: 18 months
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC--HOPE Division
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: Univeristy of California San Francisco HDF Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Cancer Institute
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Sutro Biopharma
name: Arturo Molina, MD
role: STUDY_DIRECTOR
References: