Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03748186
Recruitment Status : Recruiting
First Posted : November 20, 2018
Last Update Posted : July 18, 2019
Sponsor:
Information provided by (Responsible Party):
Sutro Biopharma, Inc.

Brief Summary:
First-in-human Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-002 given intravenously every 3 weeks.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Ovarian Carcinoma Ovary Cancer Endometrial Cancer Endometrioid Adenocarcinoma Fallopian Tube Cancer Primary Peritoneal Carcinoma Drug: STRO-002 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 dose (RP2D) and to evaluate the safety, tolerability, and preliminary anti-tumor activity of STRO-002 in adult subjects with advanced epithelial ovarian cancer (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 eligible for this study exhibit advanced relapsed and/or progressive disease. The study will consist of two parts: Part 1, dose escalation, and Part 2, dose expansion.

Part 1 (dose escalation) will enroll subjects with relapsed and/or progressive ovarian, fallopian tube or primary peritoneal cancer. Part 2 (dose expansion) will enroll subjects with relapsed and/or progressive ovarian, fallopian tube or primary peritoneal cancer (Cohort A) and subjects with relapsed and/or progressive epithelial endometrial cancer with sufficient FolRα expression per IHC as assessed by Sponsor (Cohort B).

During dose escalation (Part 1), the initial three dose levels will be evaluated with an N-of-1 approach followed by a standard 3+3 enrollment for all subsequent dose levels. Subjects with endometrial cancer will not be enrolled in the dose escalation part of the study. Subjects will be dosed based on adjusted ideal body weight (AIBW). The starting dose was determined to be the human equivalent dose (HED) of 1/6 the highest non-severely toxic dose (HNSTD) identified in the good laboratory practice (GLP) toxicology study in cynomolgus monkeys. Subsequent doses follow a modified Fibonacci sequence for dose escalation, the second dose increases by 100% of the initial dose, and thereafter by 80%, then 60%, 50%, 40%, 30% and then 20% of the preceding doses. The first three dose levels will enroll only 1 patient unless there is an 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). Any event meeting these criteria will be reviewed and confirmed by the Safety Evaluation Team (SET). When these criteria are met then the dose is expanded with 2 additional subjects and the standard 3+3 trial design is used for all further dose levels. If these criteria are not met during the first 3 dose levels, the standard 3 +3 trial design will begin with dose level 4.

The dose escalation phase of the study will be complete when the MTD is determined and the RP2D for dose expansion is identified. After determination of the RP2D, endometrial cancer subjects (Cohort B) will be enrolled in the dose expansion part of the study and will be analyzed for preliminary efficacy independently from the ovarian (including fallopian tube and primary peritoneal) cancer cohort (Cohort A).

In both Part 1 and Part 2 of the study, STRO-002 will be dosed as an intravenous (IV) infusion on Day 1 of 21-day cycles. Clinical evaluations and/or laboratory tests will be performed 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 pharmacokinetics (PK) analysis will occur at specific times on Days 1, 2, 8, and 15 of Cycles 1 and 2, Days 1, 8 and 15 of Cycles 3 and 4 and at the end of treatment (EOT) visit. Additional clinical evaluations and lab testing may occur at the discretion of the investigator.

Subjects who receive any dose of STRO-002 will be included in safety analyses. Disease evaluations will include peripheral blood analysis and scans as appropriate. Disease status will be evaluated per RECIST 1.1 criteria. Samples will be collected to assess the PK and immunogenicity of STRO-002. Biomarkers may be assessed from 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).


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Intervention Model: Sequential Assignment
Intervention Model Description: Part 1: Dose escalation starting at human equivalent dose (HED) of 1/6 the highest non-severely toxic dose (HNSTD) identified in the good laboratory practice (GLP) toxicology study in cynomolgus monkeys. The second dose level increases by 100% of the initial dose, and thereafter by 80%, then 60%, 50%, 40%, 30% and then 20% of the preceding doses.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 Advanced Epithelial Ovarian Cancer and Endometrial Cancers
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2024


Arm Intervention/treatment
Experimental: STRO-002 treatment
STRO-002 at increasing dose levels
Drug: STRO-002
intravenous antibody drug conjugate




Primary Outcome Measures :
  1. Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002) [ Time Frame: 18 months ]
    Incidence of adverse events (AEs) observed across STRO-002 dose levels

  2. Part 1: Define the recommended phase 2 dose (RP2D) of STRO-002 [ Time Frame: 18 months ]
    Frequency of dose-limiting toxicity and exposure across STRO-002 dose levels

  3. Part 1: Define the maximum tolerated dose (MTD) of STRO-002 [ Time Frame: 18 months ]
    Frequency of dose-limiting toxicity and exposure across STRO-002 dose levels

  4. Part 2: Evaluate preliminary anti-tumor activity (ovarian, Fallopian and primary peritoneal cancer patients) [ Time Frame: 24 months ]
    Objective response rate per RECIST 1.1

  5. Part 2: Evaluate preliminary anti-tumor activity (endometrial cancer patients) [ Time Frame: 24 months ]
    Objective response rate per RECIST 1.1


Secondary Outcome Measures :
  1. Part 1: Characterize the pharmacokinetics (PK) of STRO-002 by measuring the maximum plasma concentration (Cmax) [ Time Frame: 18 months ]
    Measurement of maximum plasma concentration after the administration of STRO-002

  2. Part 1: Characterize the PK of STRO-002 by measuring the half-life (t1/2) of STRO-002 [ Time Frame: 18 months ]
    Measurement of terminal half-life of STRO-002 after the administration of STRO-002

  3. Part 1: Characterize the PK of STRO-002 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf) [ Time Frame: 18 months ]
    Measurement of AUC to infinity (AUCinf)

  4. Part 1: Characterize the PK of STRO-002 by measuring the clearance (CL) [ Time Frame: 18 months ]
    Measurement of total body clearance

  5. Part 1: Characterize the PK of STRO-002 by measuring the the steady state volume of distribution (Vss) [ Time Frame: 18 months ]
    Measurement of steady state volume of distribution

  6. Part 1: Assess the formulation of anti-drug antibodies to STRO-002 [ Time Frame: 18 months ]
    Circulating anti-drug antibodies (ADAs) formed to STRO-002

  7. Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002) [ Time Frame: 24 months ]
    Number of patients with abnormal laboratory values and/or adverse events related to STRO-002 treatment

  8. Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of duration of response (DOR) in patients treated with STRO-002 [ Time Frame: 24 months ]
    Duration of response per RECIST 1.1

  9. Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-002 [ Time Frame: 24 months ]
    Progression-free survival per RECIST 1.1

  10. Part 2: Evaluate preliminary effect of STRO-002 treatment on CA-125 levels [ Time Frame: 24 months ]
    Response assessment based on the Gynecologic Cancer Intergroup (GCIG) criteria

  11. Part 2: Characterize the PK of STRO-002 by measuring the maximum plasma concentration (Cmax) [ Time Frame: 24 months ]
    Measurement of maximum plasma concentration (Cmax) after the administration of STRO-002

  12. Part 2: Characterize the PK of STRO-002 by measuring the area under the plasma concentration versus time curve (AUC) [ Time Frame: 24 months ]
    Measurement of AUC to infinity (AUC inf)

  13. Part 2: Characterize the PK of STRO-002 by measuring the clearance (CL) [ Time Frame: 24 months ]
    Measurement of total body clearance


Other Outcome Measures:
  1. Part 1: Preliminary assessment of the anti-tumor activity of STRO-002 [ Time Frame: 18 months ]
    Objective response rate per RECIST 1.1



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Patients are required to have ovarian, fallopian, primary peritoneal or endometrial cancer.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmation of diagnosis
  2. Relapsed or relapsed/refractory disease
  3. Age ≥ 18 years
  4. ECOG performance status (0-1)
  5. Life expectancy > 3 months
  6. Adequate bone marrow, liver and renal functions
  7. QTcF <500 msec
  8. Ability to comply with treatment, PK and test schedules

Exclusion Criteria:

  1. Low grade ovarian carcinoma (Grade 1).
  2. Clear cell, mucinous and sarcomatous ovarian carcinomas.
  3. Prior treatment with a FolRα-targeting ADCs or FolRα-targeting vaccines
  4. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment
  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: Physiologic replacement and use of topical or inhaled corticosteroids are allowed.
  8. Clinically significant cardiac disease
  9. Clinically significant pre-exisiting ocular disorders
  10. Significant concurrent, uncontrolled medical condition
  11. History or clinical signs of meningeal or active CNS involvement
  12. Known severe chronic obstructive pulmonary disease or asthma
  13. History of significant cerebrovascular disease
  14. Known Human Immunodeficiency Virus seropositivity
  15. Positive serology for hepatitis B defined by a positive test for HBsAg
  16. Concurrent participation in another therapeutic treatment trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03748186


Contacts
Layout table for location contacts
Contact: Shannon Matheny, Ph.D. 6506764610 STRO-002ClinDev@sutrobio.com
Contact: Michael Palumbo 6506764689 STRO-002ClinDev@sutrobio.com

Locations
Layout table for location information
United States, Colorado
Rocky Mountain Cancer Center Recruiting
Aurora, Colorado, United States, 80012
Contact: Patty Gibson, RN, BSN    303-418-7639    Patricia.Gibson@usoncology.com   
Principal Investigator: Sami Diab, MD         
United States, Florida
Miami Cancer Institue, Baptist Health South Florida Recruiting
Miami, Florida, United States, 33176
Contact: Isabel Moya, BSCR, CCRP    786-527-8861    IsabelMoy@baptisthealth.net   
Principal Investigator: John Diaz, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Hatti Koning    773-834-5722    hkoning@medicine.bsd.uchicago.edu   
Principal Investigator: John Moroney, MD         
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Karyn Mianulli, BSN, RN    702-952-3443    karyn.mianulli@usoncology.com   
Principal Investigator: Fadi Braiteh, MD         
United States, North Carolina
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Heather Neagle, RN, BSN    980-442-2303    Heather.Neagle@atriumhealth.org   
Principal Investigator: R. Wendel Naumann, MD         
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Cynthia Perez, BS, CCRP    215-955-6407    cynthia.perez@jefferson.edu   
Principal Investigator: Russell Schilder, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Sheetal Champaneria    615-329-6875    sheetal.champaneria@sarahcannon.com   
Principal Investigator: Erika Hamilton, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Suki Skandarajah    414-805-5337    sskandarajah@mcw.edu   
Principal Investigator: Denise Uyar, MD         
Sponsors and Collaborators
Sutro Biopharma, Inc.
Investigators
Layout table for investigator information
Study Chair: Arturo Molina, MD Sutro Biopharma

Layout table for additonal information
Responsible Party: Sutro Biopharma, Inc.
ClinicalTrials.gov Identifier: NCT03748186     History of Changes
Other Study ID Numbers: STRO-002-GM1
First Posted: November 20, 2018    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endometrial Neoplasms
Fallopian Tube Neoplasms
Carcinoma, Endometrioid
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Uterine Neoplasms
Uterine Diseases
Fallopian Tube Diseases
Antibodies
Immunoconjugates
Folic Acid Antagonists
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action