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.