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

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 (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 2 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 2 dose levels were evaluated with an N-of-1 approach followed by a standard 3+3 enrollment for all subsequent dose levels. Subjects with endometrial cancer were not enrolled in the dose escalation part of the study. Subjects were dosed based on adjusted ideal body weight (AIBW). The starting dose of 0.5 mg/kg 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 increased by 100% of the initial dose, and thereafter by 80%, 60%, 50%, 40%, 30% and then 20% of the preceding doses. The first 2 dose levels (0.5 mg/kg and 1.0 mg/kg) enrolled only 1 subject, as there was no instance of a treatment-related, clinically relevant grade 2 nonhematologic toxicity or a grade 3 hematologic toxicity of any type observed during cycle 1 (first 21 days).

The dose escalation phase of the study was completed with the enrollment of 39 subjects over 9 dose levels (0.5-6.4 mg/kg). An MTD was not found during dose escalation. After the subjects treated at the 6.0 mg/kg dose level were reviewed by the Safety Evaluation Team, additional subjects were treated at 5.2 mg/kg, 5.6 mg/kg and 6.0 mg/kg to further characterize the safety profile. Two dose-limiting toxicity (DLT) events were observed, peripheral neuropathy at 6.0 mg/kg and bone pain at 6.4 mg/kg. Two doses, 4.3 mg/kg and 5.2 mg/kg, will be further evaluated in the dose expansion phase for safety and efficacy based on initial findings during dose escalation

During dose expansion (Part 2), the study will enroll 2 populations, ovarian cancer (Cohort A) and endometrial cancer (Cohort B). Enrollment into Cohort A will be initiated with this protocol amendment. Subjects enrolled with ovarian cancer (including fallopian tube and primary peritoneal, Cohort A) are not required to have a minimum amount of FolRα expression, as their tumors will be assessed retrospectively by the ICH FolRα assay.

Enrollment into Cohort B dose expansion (endometrial cancer) will not be initiated until a subsequent protocol amendment, which will define the dosing regimen and minimum FolRα expression required for study eligibility. The dose regimen for Expansion Cohort B will be selected based on Part 1 dose escalation and emerging Expansion Cohort A data (safety and pharmacokinetics [PK]). Selection of a FolRα expression cutoff for Expansion Cohort B eligibility will be determined as part of validation work with an IHC FolRα assay.

In dose expansion, Cohort A (both dose levels) and Cohort B will be analyzed independently for preliminary efficacy.

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 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. 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 Response Evaluation Criteria in Solid Tumors (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).