Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate in Ovarian & Endometrial Cancers
- Conditions
- Endometrioid AdenocarcinomaOvarian CancerOvarian CarcinomaPrimary Peritoneal CarcinomaOvary CancerEndometrial CancerFallopian Tube Cancer
- Interventions
- Registration Number
- NCT03748186
- Lead Sponsor
- Sutro Biopharma, Inc.
- Brief Summary
Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-002 given intravenously every 3 weeks.
- Detailed Description
This study is a phase 1, open-label, multicenter, dose-escalation study with dose expansion to identify the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D) and to evaluate the safety, tolerability, and preliminary antitumor activity of STRO-002 in adult subjects with advanced epithelial ovarian cancer (EOC), including fallopian or primary peritoneal cancer, and endometrial cancer. Fallopian tube and primary peritoneal cancers are treated in the same manner as epithelial ovarian cancers and are thus included in this phase 1 study. Subjects enrolled in the study will be required to have progressive or recurrent disease after standard approved therapy as defined in the study eligibility criteria. The study has completed dose escalation and is currently in dose expansion, enrolling endometrial and ovarian cancer subjects.
All subjects enrolled on the study are required to have tumor tissue for determining folate receptor alpha (FolRα) expression levels, either from a prior surgery or tumor biopsy or from a biopsy performed during study screening. The testing for FolRα is done via an ICH assay. A minimum level of FolRα expression is required for enrollment for endometrial cancer but not for ovarian cancer.
Study drug, STRO-002, is administered by intravenous (IV) infusion on day 1 of 21-day cycles. Clinical evaluations and/or laboratory tests will be performed at a pre-specified schedule-weekly for cycles 1-4, and at the beginning of every cycle starting with cycle 5 as described in the schedule of assessments. Samples for PK analysis will occur at specific times on days 1, 8, and 15 of cycles 1 and 4, Day 1 of cycles 2, 3, and 5 and at the end of treatment (EOT) visit. The study requires imaging with a CT or MRI scan of the chest abdomen and pelvis at screening, every 6 weeks after enrollment for the first 18 weeks, then every 9 weeks, and at the end of treatment (EOT) visit. Additional X-rays may be required to confirm disease responses and per local institution standard of care.
Additional clinical evaluations and lab testing may occur at the discretion of the investigator.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 136
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Age ≥ 18 years
-
Measurable disease per RECIST 1.1
-
ECOG performance status (0-1)
-
Life expectancy > 3 months
-
Pathological confirmation of disease under study (historical information, diagnosis, pathology report, etc)
- Expansion Cohorts A and C: High-grade serous EOC, fallopian tube cancer or primary peritoneal cancer
- Expansion Cohort B: Histologically diagnosed epithelial endometrial cancer (endometrioid and serous adenocarcinomas; undifferentiated carcinoma; mixed epithelial carcinoma; or adenocarcinoma NOS)
-
Relapsed and/or progressive disease
-
Dose Expansion Cohorts A and C (Ovarian Cancer):
- Platinum resistant and received 1-3 prior regimens or
- Platinum sensitive and either:
- Progressed after 2 prior lines of platinum therapy (regardless of platinum status)and received 2-3 prior regimens or
- Progressed after 1 line of platinum therapy and 1 line of non-platinum therapy and received a total of 2-3 prior regimens if contraindicated to receive second platinum regimen.
-
Dose Expansion Cohort B (Endometrial Cancer):
- Relapsed or progression after at least 1 platinum-based chemotherapy regimen or 1 immunotherapy-based regimen but not to exceed more than 3 prior regimens.
-
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Fresh or archival tumor tissue samples
- Low grade (grade 1) ovarian carcinoma, clear cell, mucinous and sarcomatous ovarian carcinomas (Cohort A).
- Endometrial carcinosarcomas, leiomyosarcoma and stromal sarcomas (Cohort B).
- Prior treatment with a FolRα-targeting ADCs or FolRα-targeting vaccines
- Platinum-refractory during frontline treatment (Cohorts A and C)
- Greater than 3 lines of prior treatment
- History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment
- Preexisting clinically significant ocular disorders, clinically significant pre-exisiting ocular disorders, severe chronic obstructive pulmonary disease or asthma, clinically significant cardiac or cerebrovascular disease, or other significant concurrent, uncontrolled medical condition
- Metastatic central nervous system or meningeal disease
- Concurrent participation in another therapeutic treatment trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description STRO-002 treatment STRO-002 Dose Escalation: STRO-002 at increasing dose levels Dose Expansion: STRO-002 at 4.3 mg/kg and 5.2 mg/kg
- Primary Outcome Measures
Name Time Method Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002) 18 months Incidence of adverse events (AEs) observed across STRO-002 dose levels
Part 1: Define the recommended phase 2 dose (RP2D) of STRO-002 18 months Frequency of dose-limiting toxicity and exposure across STRO-002 dose levels
Part 1: Define the maximum tolerated dose (MTD) of STRO-002 18 months Frequency of dose-limiting toxicity and exposure across STRO-002 dose levels
Part 2: Evaluate preliminary anti-tumor activity (ovarian, Fallopian and primary peritoneal cancer patients) 24 months Objective response rate per RECIST 1.1
Part 2: Evaluate preliminary anti-tumor activity (endometrial cancer patients) 24 months Objective response rate per RECIST 1.1
- Secondary Outcome Measures
Name Time Method Part 1: Assess the formulation of anti-drug antibodies to STRO-002 18 months Circulating anti-drug antibodies (ADAs) formed to STRO-002
Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of duration of response (DOR) in patients treated with STRO-002 24 months Duration of response per RECIST 1.1
Part 2: Characterize the PK of STRO-002 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-002 by measuring the clearance (CL) 24 months Measurement of total body clearance
Part 1: Characterize the pharmacokinetics (PK) of STRO-002 by measuring the maximum plasma concentration (Cmax) 18 months Measurement of maximum plasma concentration after the administration of STRO-002
Part 1: Characterize the PK of STRO-002 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf) 18 months Measurement of AUC to infinity (AUCinf)
Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-002 24 months Progression-free survival per RECIST 1.1
Part 2: Characterize the PK of STRO-002 by measuring the maximum plasma concentration (Cmax) 24 months Measurement of maximum plasma concentration (Cmax) after the administration of STRO-002
Part 1: Characterize the PK of STRO-002 by measuring the half-life (t1/2) of STRO-002 18 months Measurement of terminal half-life of STRO-002 after the administration of STRO-002
Part 1: Characterize the PK of STRO-002 by measuring the clearance (CL) 18 months Measurement of total body clearance
Part 1: Characterize the PK of STRO-002 by measuring the the steady state volume of distribution (Vss) 18 months Measurement of steady state volume of distribution
Part 2: Evaluate preliminary effect of STRO-002 treatment on CA-125 levels 24 months Response assessment based on the Gynecologic Cancer Intergroup (GCIG) criteria
Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002) 24 months Number of patients with abnormal laboratory values and/or adverse events related to STRO-002 treatment
Trial Locations
- Locations (27)
Miami Cancer Institue, Baptist Health South Florida
🇺🇸Miami, Florida, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Minnesota Oncology Hematology
🇺🇸Minneapolis, Minnesota, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Arizona Oncology - Tucson
🇺🇸Tucson, Arizona, United States
UCLA Jonsson Comprehensive Cancer Center Clinical Research Unit
🇺🇸Los Angeles, California, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Sutter Health- Palo Alto Medical Foundation
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Center
🇺🇸Aurora, Colorado, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Augusta Oncology
🇺🇸Augusta, Georgia, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Maryland Oncology Hematology
🇺🇸Rockville, Maryland, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
NYU Langone Medical Center
🇺🇸New York, New York, United States
University of Cincinnati Cancer Institute
🇺🇸Cincinnati, Ohio, United States
Cancer Care Northwest-South Spokane
🇺🇸Spokane, Washington, United States
Ohio State University, James Cancer Center
🇺🇸Columbus, Ohio, United States
Prisma Health
🇺🇸Greenville, South Carolina, United States
Clínica Universidad de Navarra -Madrid
🇪🇸Madrid, Spain
Vall d'Hebron Institut d'Oncologia
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro - CIOCC
🇪🇸Madrid, Spain
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States