Study of STRO-001, an Anti-CD74 Antibody Drug Conjugate, in Patients With Advanced B-Cell Malignancies
Study Details
Study Description
Brief Summary
First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-001 given intravenously every 3 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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.
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: STRO-001 intravenous |
Drug: STRO-001
intravenous antibody drug conjugate
|
Outcome Measures
Primary Outcome Measures
- Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001) [18 months]
Incidence of adverse events (AEs) observed across STRO-001 dose levels
- Part 1: Define the recommended phase 2 dose (RP2D) and maximum tolerated dose (MTD) of STRO-001 [18 months]
Frequency of dose-limiting toxicity and exposure across STRO-001 dose levels
- Part 2: Evaluate preliminary anti-tumor activity (multiple myeloma patients) [24 months]
Objective response rates per International Myeloma Working Group (IMWG) criteria for response assessment
- Part 2: Evaluate preliminary anti-tumor activity (NHL patients) [24 months]
Objective response rates per the Lugano classification for response assessment
Secondary Outcome Measures
- Part 1: Characterize the pharmacokinetics (PK) of STRO-001 by measuring the maximum plasma concentration (Cmax) [18 months]
Measurement of maximum plasma concentration after the administration of STRO-001
- Part 1: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001 [18 months]
Measurement of terminal half-life of STRO-001 after the administration of STRO-001
- Part 1: Characterize the PK of STRO-001 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf) [18 months]
Measurement of AUC to infinity (AUCinf)
- Part 1: Characterize the PK of STRO-001 by measuring the clearance (CL) [18 months]
Measurement of total body clearance
- Part 1: Characterize the PK of STRO-001 by measuring the the steady state volume of distribution (Vss) [18 months]
Measurement of steady state volume of distribution
- Part 1: Assess the immunogenic potential of STRO-001 [18 months]
Evaluation and quantitation of circulating anti-drug antibodies (ADAs) over time
- Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-001) [24 months]
Number of patients with abnormal laboratory values and/or adverse events related to STRO-001 treatment
- Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of duration of response (DOR) in patients treated with STRO-001 [24 months]
Each cohort will be analyzed independently
- Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-001 [24 months]
Each cohort will be analyzed independently
- Part 2: Characterize the PK of STRO-001 by measuring the maximum plasma concentration (Cmax) [24 months]
Measurement of maximum plasma concentration after the administration of STRO-001
- Part 2: Characterize the PK of STRO-001 by measuring the half-life (t1/2) of STRO-001 [24 months]
Measurement of terminal half-life of STRO-001 after the administration of STRO-001
- Part 2: Characterize the PK of STRO-001 by measuring the area under the plasma concentration versus time curve (AUC) [24 months]
Measurement of AUC to infinity (AUC inf)
- Part 2: Characterize the PK of STRO-001 by measuring the clearance (CL) [24 months]
Measurement of total body clearance
Other Outcome Measures
- Part 1: Preliminary assessment of the anti-tumor activity of STRO-001 (multiple myeloma patients) [18 months]
Objective response rates per IMWG criteria for response assessment
- Part 1: Preliminary assessment of the anti-tumor activity of STRO-001 (NHL) [18 months]
Objective response rates per the Lugano classification for response assessment (NHL patients)
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Confirmation of diagnosis
-
Relapsed or relapsed/refractory disease
-
Age ≥ 18 years
-
ECOG performance status (0-2)
-
Life expectancy > 3 months
-
Adequate bone marrow and renal functions
-
QTcF <500 msec
-
Ability to comply with treatment, PK and test schedules
-
NHL only- at least one measurable lesion
Key Exclusion Criteria:
-
Active plasma cell leukemia and/or leukemic manifestations of lymphoma
-
Known amyloidosis (MM patients)
-
Chronic lymphocytic leukemia and Richter's transformation, and prolymphocytic leukemia (NHL subjects)
-
T-cell malignancy
-
Sensory or motor neuropathy ≥ grade 2
-
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
-
Ongoing immunosuppressive therapy, including systemic corticosteroids. Note: Subjects may be using topical or inhaled corticosteroids.
-
Clinically significant cardiac disease
-
Significant concurrent, uncontrolled medical condition
-
History or clinical signs of meningeal or active CNS involvement
-
Known severe chronic obstructive pulmonary disease or asthma
-
History of significant cerebrovascular disease
-
Known Human Immunodeficiency Virus seropositivity
-
Positive serology for hepatitis B defined by a positive test for HBsAg
-
Concurrent participation in another therapeutic treatment trial
-
High screening liver function tests
-
Prior treatment with CD74 targeting therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35294 |
| 2 | Arizona Oncology Associates, PC--HOPE Division | Tucson | Arizona | United States | 85711 |
| 3 | City of Hope Medical Center | Duarte | California | United States | 91010 |
| 4 | UC Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 5 | Univeristy of California San Francisco HDF Comprehensive Cancer Center | San Francisco | California | United States | 94143 |
| 6 | Rocky Mountain Cancer Center | Aurora | Colorado | United States | 80012 |
| 7 | Emory University Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 8 | Indiana University Health Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 9 | University of Kansas Cancer Center | Fairway | Kansas | United States | 66205 |
| 10 | University of Maryland Medical Center | Baltimore | Maryland | United States | 21201 |
| 11 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 12 | Henry Ford Cancer Institute | Detroit | Michigan | United States | 48202 |
| 13 | Icahn School of Medicine at Mount Sinai | New York | New York | United States | 10029 |
| 14 | Weill Cornell Medicine | New York | New York | United States | 10065 |
| 15 | Willamette Valley Cancer Institute and Research Center | Eugene | Oregon | United States | 97401 |
| 16 | Texas Oncology | Austin | Texas | United States | 78705 |
| 17 | Texas Oncology - Baylor Charles A. Sammons Cancer Center | Dallas | Texas | United States | 75246 |
| 18 | UT Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 19 | Texas Oncology - Fort Worth Cancer Center | Fort Worth | Texas | United States | 76104 |
| 20 | UT Health San Antonio | San Antonio | Texas | United States | 78229 |
| 21 | Virginia Cancer Specialists | Fairfax | Virginia | United States | 22031 |
| 22 | West Virginia University | Morgantown | West Virginia | United States | 26505 |
| 23 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Sutro Biopharma, Inc.
Investigators
- Study Director: Arturo Molina, MD, Sutro Biopharma
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- ASH conference, Dec 2017 oral presentation NHL abstract
- ASH conference, Dec 2017 poster presentation multiple myeloma abstract
Publications
None provided.- STRO-001-BCM1