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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Ovarian Cancer, Ovarian Carcinoma, Ovary Cancer, Endometrial Cancer, Endometrioid Adenocarcinoma, Fallopian Tube Cancer, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Drug: STRO-002


Participation Criteria
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Eligibility Criteria
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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 Cohorts A and C: 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 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. 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 (Cohorts A and C) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STRO-002 treatment<br>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<br>* intravenous antibody drug conjugate<br>|

What is the study measuring?
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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 |