Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate in Ovarian & Endometrial Cancers

A Phase 1 Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody-Drug Conjugate (ADC), in Patients With Advanced Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) and Endometrial Cancers

Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-002 given intravenously every 3 weeks.

Study Overview

• Status: Recruiting
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Endometrial Cancer; Ovarian Carcinoma; Endometrioid Adenocarcinoma; Ovary Cancer; Primary Peritoneal Carcinoma
• Intervention / Treatment: Drug: STRO-002

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.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Michael Palumbo; Phone Number: 650-676-4689; Email: STRO-002ClinDev@sutrobio.com

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Vall d'Hebron Institut d'Oncologia
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario HM Sanchinarro - CIOCC
  • Madrid, Spain, 28027
    • Recruiting
    • Clinica Universidad de Navarra -Madrid
• United States
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Recruiting
      • Arizona Oncology - Tucson
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Jonsson Comprehensive Cancer Center Clinical Research Unit
    • San Francisco, California, United States, 94109
      • Recruiting
      • Sutter Health- Palo Alto Medical Foundation
      • Contact: Chris Argueta; Phone Number: 415-600-5848; Email: arguec1@sutterhealth.org
      • Principal Investigator: John Chan, MD
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Recruiting
      • Rocky Mountain Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale School of Medicine
  • Florida
    • Miami, Florida, United States, 33176
      • Recruiting
      • Miami Cancer Institue, Baptist Health South Florida
    • Tampa, Florida, United States, 33606
      • Recruiting
      • University of South Florida
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Augusta Oncology
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Recruiting
      • Maryland Oncology Hematology
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Recruiting
      • Minnesota Oncology Hematology
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Recruiting
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati Cancer Institute
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University, James Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Prisma Health
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists
  • Washington
    • Spokane, Washington, United States, 99204
      • Recruiting
      • Cancer Care Northwest-South Spokane
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Recruiting
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Measurable disease per RECIST 1.1
3. ECOG performance status (0-1)
4. Life expectancy > 3 months

5. Pathological confirmation of disease under study (historical information, diagnosis, pathology report, etc)

   1. Expansion Cohorts A and C: High-grade serous EOC, fallopian tube cancer or primary peritoneal cancer
   2. Expansion Cohort B: Histologically diagnosed epithelial endometrial cancer (endometrioid and serous adenocarcinomas; undifferentiated carcinoma; mixed epithelial carcinoma; or adenocarcinoma NOS)

6. Relapsed and/or progressive disease

   1. 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.

   2. 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.
7. Fresh or archival tumor tissue samples

Exclusion Criteria:

1. Low grade (grade 1) ovarian carcinoma, clear cell, mucinous and sarcomatous ovarian carcinomas (Cohort A).
2. Endometrial carcinosarcomas, leiomyosarcoma and stromal sarcomas (Cohort B).
3. Prior treatment with a FolRα-targeting ADCs or FolRα-targeting vaccines
4. Platinum-refractory during frontline treatment (Cohorts A and C)
5. Greater than 3 lines of prior treatment
6. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment
7. 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
8. Metastatic central nervous system or meningeal disease
9. Concurrent participation in another therapeutic treatment trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: STRO-002 treatment; Dose Escalation: STRO-002 at increasing dose levels Dose Expansion: STRO-002 at 4.3 mg/kg and 5.2 mg/kg	Drug: STRO-002; 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-002)	Incidence of adverse events (AEs) observed across STRO-002 dose levels	18 months
Part 1: Define the recommended phase 2 dose (RP2D) of STRO-002	Frequency of dose-limiting toxicity and exposure across STRO-002 dose levels	18 months
Part 1: Define the maximum tolerated dose (MTD) of STRO-002	Frequency of dose-limiting toxicity and exposure across STRO-002 dose levels	18 months
Part 2: Evaluate preliminary anti-tumor activity (ovarian, Fallopian and primary peritoneal cancer patients)	Objective response rate per RECIST 1.1	24 months
Part 2: Evaluate preliminary anti-tumor activity (endometrial cancer patients)	Objective response rate per RECIST 1.1	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Characterize the pharmacokinetics (PK) of STRO-002 by measuring the maximum plasma concentration (Cmax)	Measurement of maximum plasma concentration after the administration of STRO-002	18 months
Part 1: Characterize the PK of STRO-002 by measuring the half-life (t1/2) of STRO-002	Measurement of terminal half-life of STRO-002 after the administration of STRO-002	18 months
Part 1: Characterize the PK of STRO-002 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-002 by measuring the clearance (CL)	Measurement of total body clearance	18 months
Part 1: Characterize the PK of STRO-002 by measuring the the steady state volume of distribution (Vss)	Measurement of steady state volume of distribution	18 months
Part 1: Assess the formulation of anti-drug antibodies to STRO-002	Circulating anti-drug antibodies (ADAs) formed to STRO-002	18 months
Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002)	Number of patients with abnormal laboratory values and/or adverse events related to STRO-002 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-002	Duration of response per RECIST 1.1	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-002	Progression-free survival per RECIST 1.1	24 months
Part 2: Evaluate preliminary effect of STRO-002 treatment on CA-125 levels	Response assessment based on the Gynecologic Cancer Intergroup (GCIG) criteria	24 months
Part 2: Characterize the PK of STRO-002 by measuring the maximum plasma concentration (Cmax)	Measurement of maximum plasma concentration (Cmax) after the administration of STRO-002	24 months
Part 2: Characterize the PK of STRO-002 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-002 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-002	Objective response rate per RECIST 1.1	18 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2019
• Primary Completion (ANTICIPATED): August 1, 2024
• Study Completion (ANTICIPATED): August 1, 2024

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: November 19, 2018
• First Posted (ACTUAL): November 20, 2018

Study Record Updates

• Last Update Posted (ESTIMATE): February 9, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Carcinoma; Ovarian Neoplasms; Fallopian Tube Neoplasms; Endometrial Neoplasms; Carcinoma, Ovarian Epithelial; Carcinoma, Endometrioid
• Other Study ID Numbers: STRO-002-GM1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No