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

Sponsor

Sutro Biopharma, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03748186

Collaborator

(none)

160

Enrollment

Locations

Arm

Anticipated Duration (Months)

6.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 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 Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

The study is a modified 3+3 dose escalation study with a dose expansion. Dose escalation is in advanced ovarian cancer patients with relapsed or refractory disease to standard approved therapy. Dose expansion includes 2 cancer populations, ovarian cancer and endometrial cancer. The ovarian cancer expansion cohort (Cohort A) is a dose ranging design with randomization into 2 dose levels of STRO-002, 4.3 mg/kg and 5.2 mg/kg. Dose expansion in endometrial cancer (Cohort B) is a single dose cohort design, STRO-002 5.2 mg/kg. Endometrial subjects with prior pelvic irradiation will start treatment of STRO-002 at 4.3 mg/kg with step up to 5.2 mg/kg.The study is a modified 3+3 dose escalation study with a dose expansion. Dose escalation is in advanced ovarian cancer patients with relapsed or refractory disease to standard approved therapy. Dose expansion includes 2 cancer populations, ovarian cancer and endometrial cancer. The ovarian cancer expansion cohort (Cohort A) is a dose ranging design with randomization into 2 dose levels of STRO-002, 4.3 mg/kg and 5.2 mg/kg. Dose expansion in endometrial cancer (Cohort B) is a single dose cohort design, STRO-002 5.2 mg/kg. Endometrial subjects with prior pelvic irradiation will start treatment of STRO-002 at 4.3 mg/kg with step up to 5.2 mg/kg.

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

Actual Study Start Date :

Feb 1, 2019

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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

Other Outcome Measures

Part 1: Preliminary assessment of the anti-tumor activity of STRO-002 [18 months]
Objective response rate per RECIST 1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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 Cohort A: 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 Cohort A (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.

Fresh or archival tumor tissue samples

Exclusion Criteria:

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 (Cohort A)
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology - Tucson	Tucson	Arizona	United States	85711
2	UCLA Jonsson Comprehensive Cancer Center Clinical Research Unit	Los Angeles	California	United States	90095
3	Rocky Mountain Cancer Center	Aurora	Colorado	United States	80012
4	Yale School of Medicine	New Haven	Connecticut	United States	06520
5	Miami Cancer Institue, Baptist Health South Florida	Miami	Florida	United States	33176
6	University of South Florida	Tampa	Florida	United States	33606
7	Augusta Oncology	Augusta	Georgia	United States	30912
8	University of Chicago	Chicago	Illinois	United States	60637
9	Maryland Oncology Hematology	Rockville	Maryland	United States	20850
10	Minnesota Oncology Hematology	Minneapolis	Minnesota	United States	55404
11	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
12	NYU Langone Medical Center	New York	New York	United States	10016
13	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
14	University of Cincinnati Cancer Institute	Cincinnati	Ohio	United States	45267
15	Ohio State University, James Cancer Center	Columbus	Ohio	United States	43210
16	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
17	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
18	Prisma Health	Greenville	South Carolina	United States	29605
19	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
20	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
21	Cancer Care Northwest-South Spokane	Spokane	Washington	United States	99204
22	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
23	Vall d'Hebron Institut d'Oncologia	Barcelona		Spain	08035
24	Clínica Universidad de Navarra -Madrid	Madrid		Spain	28027
25	Hospital Universitario La Paz	Madrid		Spain	28046
26	Hospital Universitario HM Sanchinarro - CIOCC	Madrid		Spain	28050