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

Ovarian Cancer Clinical Trial

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 Patients With Advanced Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) and Endometrial Cancers

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03748186
• Other study ID #: STRO-002-GM1
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 1, 2019
• Est. completion date: November 2024

Study information

• Verified date: June 2024
• Source: Sutro Biopharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: November 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 FolRa-targeting ADCs or FolRa-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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Endometrioid
• Carcinoma, Ovarian Epithelial
• Endometrial Cancer
• Endometrial Neoplasms
• Endometrioid Adenocarcinoma
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Carcinoma
• Ovarian Neoplasms
• Ovary Cancer
• Primary Peritoneal Carcinoma

Intervention

Drug:
• STRO-002
intravenous antibody drug conjugate

Locations

Country	Name	City	State
Spain	Vall d'Hebron Institut d'Oncologia	Barcelona
Spain	Clínica Universidad de Navarra -Madrid	Madrid
Spain	Hospital Universitario HM Sanchinarro - CIOCC	Madrid
Spain	Hospital Universitario La Paz	Madrid
United States	Augusta Oncology	Augusta	Georgia
United States	Rocky Mountain Cancer Center	Aurora	Colorado
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	Ohio State University, James Cancer Center	Columbus	Ohio
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Prisma Health	Greenville	South Carolina
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	UCLA Jonsson Comprehensive Cancer Center Clinical Research Unit	Los Angeles	California
United States	Miami Cancer Institue, Baptist Health South Florida	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Minnesota Oncology Hematology	Minneapolis	Minnesota
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	NYU Langone Medical Center	New York	New York
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Maryland Oncology Hematology	Rockville	Maryland
United States	Sutter Health- Palo Alto Medical Foundation	San Francisco	California
United States	Cancer Care Northwest-South Spokane	Spokane	Washington
United States	University of South Florida	Tampa	Florida
United States	Arizona Oncology - Tucson	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Sutro Biopharma, Inc.

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Part 1: Preliminary assessment of the anti-tumor activity of STRO-002	Objective response rate per RECIST 1.1	18 months
Primary	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
Primary	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
Primary	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
Primary	Part 2: Evaluate preliminary anti-tumor activity (ovarian, Fallopian and primary peritoneal cancer patients)	Objective response rate per RECIST 1.1	24 months
Primary	Part 2: Evaluate preliminary anti-tumor activity (endometrial cancer patients)	Objective response rate per RECIST 1.1	24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 1: Characterize the PK of STRO-002 by measuring the clearance (CL)	Measurement of total body clearance	18 months
Secondary	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
Secondary	Part 1: Assess the formulation of anti-drug antibodies to STRO-002	Circulating anti-drug antibodies (ADAs) formed to STRO-002	18 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 2: Characterize the PK of STRO-002 by measuring the clearance (CL)	Measurement of total body clearance	24 months