A Study of STRO-002, an Anti-Folate Receptor Alpha Antibody Drug Conjugate, in Combination With Bevacizumab in Epithelial Ovarian Cancer

Inclusion Criteria

• Age ≥ 18 years.
• ECOG 0-1
• Life expectancy > 3 months
• High Grade serous epithelial ovarian cancer (EOC), fallopian tube or primary peritoneal cancer with pathology report documentation of tumor type.
• At least one measurable target lesion per RECIST v1.1.
• Tumor tissue for FolRα expression testing prior to enrollment.
• For dose escalation: tissue may be from either archival tumor tissue or from a biopsy performed during screening.
• For dose expansion part of the study, tissue from both archival tumor tissue and a biopsy performed during screening is required.
• Adequate bone marrow function defined as:
• Absolute neutrophil count (ANC) ≥1500/μL
• Hemoglobin ≥ 9g/dL
• Platelet count ≥ 100 x 10^3/μL
• Adequate liver function defined as:
• ALT and AST < 2.5 x ULN
• ALP < 2.5 x ULN
• Bilirubin < 1.5 x ULN
• Adequate renal function defined as serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min. Subjects enrolling into Dose Escalation must also meet the following inclusion criteria:
• Relapsed and/or PD on last treatment regimen and one of the following:
• Primary Platinum refractory and received no more than 1 prior regimen
• Primary platinum resistant and received no more than 4 prior regimens
• Platinum sensitive and all of the following:
• received at least 2 platinum-based therapies or received 1 platinum and 1 non-platinum based therapy (if unable to receive a second platinum regimen due to toxicity) or received at least 1 platinum-based therapy (if the regimen contained a PARP inhibitor given as maintenance treatment)
• received no more than 1 additional regimen after becoming platinum resistant
• received no more than 4 prior regimens Subjects enrolling into Part 2, Dose Expansion must also meet the following inclusion criteria:
• Relapsed and/or PD on last treatment regimen and one of the following:
• Platinum resistant and received no more than 4 prior regimens
• Platinum sensitive and
• received at least 2 platinum-based therapies or received 1 platinum and 1 non-platinum based therapy (if unable to receive a second platinum regimen due to toxicity) or received at least 1 platinum-based therapy (if the regimen contained a PARP inhibitor given as maintenance treatment)
• received no more than 1 additional regimen after becoming platinum resistant
• received no more than 4 prior regimens

Exclusion Criteria

• Low grade ovarian carcinoma (Grade 1).
• Clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian carcinomas, endometrial leiomyosarcoma, and endometrial stromal sarcomas.
• Prior treatment with an ADC with a tubulin inhibitor warhead.
• Prior treatment with other FolRα targeting agents unless approved by a Sutro medical monitor or designee.
• Subjects who are primary platinum-refractory during frontline treatment are excluded from the Expansion Cohort (Allowed in Dose Escalation if no more than 1 prior regimen).
• Greater than 4 prior lines of treatment (> 1 prior if primary platinum refractory).
• Any prior toxicity that required permanent discontinuation of bevacizumab or other contraindication to receive bevacizumab per institutional guidelines.
• Previous solid organ transplantation.
• Current signs/symptoms of bowel obstruction and/or signs/symptoms of or bowel obstruction within 3 months of initiation of study treatment.
• Grade ≥2 toxicity from prior anticancer therapy with the exception of Grade 2 alopecia or Grade 2 neuropathy.
• Uncontrolled hypertension
• Sensory or motor neuropathy Grade > 1 at screening prior to initiation of study treatment.
• Potentially fatal concurrent or recent malignancy. Subjects with past or current malignancy need to be discussed with the sponsor to determine eligibility.
• Chronic or ongoing active infection requiring systemic treatment.
• Ongoing immunosuppressive therapy, including systemic corticosteroids. Note: Physiologic replacement and use of topical or inhaled corticosteroids are allowed. Dexamethasone may be used to treat chemotherapy induced nausea per institutional guidelines.
• Clinically significant cardiac disease.
• History or clinical signs of meningeal or active central nervous system involvement.
• Known severe COPD or asthma
• Active pneumonitis within 6 months of initiating study treatment.
• History of stroke or history of significant cerebrovascular disease (i.e., transient ischemic attack) within 6 months of initiation of study treatment.
• History of pulmonary embolism or any Grade 3 thromboembolic event within 6 months of initiation of study treatment.
• Known human immunodeficiency virus seropositivity.
• Active hepatitis B or hepatitis C and positive serology (unless due to vaccination or passive immunization due to immunoglobulin therapy) with the following exceptions:
• Subject has had HCV but received antiviral treatment and shows no detectible HCV viral DNA for 6 months prior to screening
• Subject has had HBV but is HBV surface antigen (HBsAg) and viral DNA negative at screening
• Subject has had HBV but received antiviral treatment and have undetectable viral DNA for 6 months prior to screening
• Concurrent participation in another therapeutic treatment trial
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
• Females who are pregnant or breastfeeding, and all women of childbearing potential unwilling to use adequate barrier contraception while on treatment and for 16 weeks after last dose of STRO-002/bevacizumab and 6 months after the last dose of bevacizumab.