Clinical trial NCT03748186: Study of STRO-002, an Anti-Folate Receptor Alpha (FolRα) Antibody Drug Conjugate in Ovarian & Endometrial Cancers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Ovarian Carcinoma
Ovary Cancer
Endometrial Cancer
Endometrioid Adenocarcinoma
Fallopian Tube Cancer
Primary Peritoneal Carcinoma
Lead sponsor: Sutro Biopharma, Inc.
Sponsor class: INDUSTRY
First posted: 2018-11-20
Enrollment: 136
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
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 cohorts are Cohort A and Cohort C. Cohort A is a dose ranging design with randomization into 2 dose levels of STRO-002, 4.3 mg/kg and 5.2mg/kg. Cohort C is a single dose cohort design, STRO-002 5.2 mg/kg with prophylactic pegfilgrastim. 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002)
timeFrame: 18 months
measure: Part 1: Define the recommended phase 2 dose (RP2D) of STRO-002
timeFrame: 18 months
measure: Part 1: Define the maximum tolerated dose (MTD) of STRO-002
timeFrame: 18 months
measure: Part 2: Evaluate preliminary anti-tumor activity (ovarian, Fallopian and primary peritoneal cancer patients)
timeFrame: 24 months
measure: Part 2: Evaluate preliminary anti-tumor activity (endometrial cancer patients)
timeFrame: 24 months
Secondary outcomes:
measure: Part 1: Characterize the pharmacokinetics (PK) of STRO-002 by measuring the maximum plasma concentration (Cmax)
timeFrame: 18 months
measure: Part 1: Characterize the PK of STRO-002 by measuring the half-life (t1/2) of STRO-002
timeFrame: 18 months
measure: Part 1: Characterize the PK of STRO-002 measuring the total area under the concentration versus time curve from zero to infinity (AUCinf)
timeFrame: 18 months
measure: Part 1: Characterize the PK of STRO-002 by measuring the clearance (CL)
timeFrame: 18 months
measure: Part 1: Characterize the PK of STRO-002 by measuring the the steady state volume of distribution (Vss)
timeFrame: 18 months
measure: Part 1: Assess the formulation of anti-drug antibodies to STRO-002
timeFrame: 18 months
measure: Part 2: Further evaluate the incidence of Treatment-Emergent Adverse Events (Safety and Tolerability of STRO-002)
timeFrame: 24 months
measure: Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of duration of response (DOR) in patients treated with STRO-002
timeFrame: 24 months
measure: Part 2: Evaluate preliminary anti-tumor efficacy with a time-to-event analysis of progression-free survival (PFS) in patients treated with STRO-002
timeFrame: 24 months
measure: Part 2: Evaluate preliminary effect of STRO-002 treatment on CA-125 levels
timeFrame: 24 months
measure: Part 2: Characterize the PK of STRO-002 by measuring the maximum plasma concentration (Cmax)
timeFrame: 24 months
measure: Part 2: Characterize the PK of STRO-002 by measuring the area under the plasma concentration versus time curve (AUC)
timeFrame: 24 months
measure: Part 2: Characterize the PK of STRO-002 by measuring the clearance (CL)
timeFrame: 24 months
Other outcomes:
measure: Part 1: Preliminary assessment of the anti-tumor activity of STRO-002
timeFrame: 18 months
Locations:
city: Tucson
country: United States
facility: Arizona Oncology - Tucson
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Jonsson Comprehensive Cancer Center Clinical Research Unit
state: California
city: San Francisco
country: United States
facility: Sutter Health- Palo Alto Medical Foundation
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Miami
country: United States
facility: Miami Cancer Institue, Baptist Health South Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Augusta
country: United States
facility: Augusta Oncology
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Rockville
country: United States
facility: Maryland Oncology Hematology
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Institute
state: Ohio
city: Columbus
country: United States
facility: Ohio State University, James Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Spokane
country: United States
facility: Cancer Care Northwest-South Spokane
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Barcelona
country: Spain
facility: Vall d'Hebron Institut d'Oncologia
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra -Madrid
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro - CIOCC
Study officials:
References: