STRO Eligibility Criteria
Inclusion Criteria
All subjects enrolling in either Part 1, Dose Escalation or Part 2, Dose Expansion must meet all the following inclusion criteria
1. Following receipt of verbal and written information about the study, the subject must provide signed informed consent before any study related activity is conducted
2. Age ≥18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
4. Life expectancy >3 months; if subject status is ‘do not intubate’ or ‘do not resuscitate’ a discussion with Sponsor physician is needed to ensure eligibility
5. Toxicities related to prior therapy, such as peripheral neuropathy and arthralgias, must have returned to grade 1 or less, except for alopecia, which can be grade 2 or less at time of enrollment
6. Adequate bone marrow function defined as
- Absolute neutrophil count (ANC) ≥1500/μL (use of growth factors to achieve this level is NOT permitted and must be stable off any growth factor within 3 weeks of first dose of study treatment)
- Hemoglobin ≥9g/dL (use of growth factors or transfusion to achieve this level is NOT permitted and must be stable off any growth factor or post transfusion within 3 weeks of the first dose of study treatment)
- Platelet count ≥75 × 103/μL (transfusion to achieve this level is NOT permitted)
7. Adequate liver function defined as
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2.5 times the upper limit of normal (ULN)
- Alkaline phosphatase (ALP) <2.5 × ULN
- Bilirubin <1.5 × ULN
8. Adequate renal function defined as creatinine clearance (CrCl) > 40 mL/min (Cockcroft-Gault equation)
9. Calculated QT interval corrected for heart rate using Fridericia correction formula (QTcF), screening and C1D1 predose ECG must be <500 msec
10. Ability to comply with treatment, PK and testing schedules
11. Subjects of childbearing potential must have a negative pregnancy test within 7 days of the first dose of study drug and be willing to use a method of birth control with adequate barrier protection. All subjects must agree to avoid pregnancy and breastfeeding/nursing while on treatment and for at least 16 weeks after the last dose of STRO-002. A woman is not of childbearing potential if she has undergone surgical sterilization (total hysterectomy or bilateral oophorectomy or bilateral tubal ligation at least 6 weeks before taking study drug) or if she is postmenopausal and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc., for at least 12 months, with an appropriate clinical profile, and there is no other cause of amenorrhea (eg, hormone therapy, prior chemotherapy)
Subjects enrolling into Part 1, Dose Escalation must also meet the following inclusion criteria
12. Pathological confirmation of disease under study (historical information, diagnosis, pathology report, etc.)
13. EOC, fallopian tube cancer or primary peritoneal cancer
14. Relapsed and/or progressive disease: progressed after treatment with at least 2 platinum containing regimens or refractory to treatment with platinum containing therapy and with no other approved treatment options
15. If available: archival tissue samples provided to Sponsor for IHC analysis (at least 5 slides)
Subjects enrolling into Part 2, Dose Expansion must also meet the following inclusion criteria
16. Pathological confirmation of disease under study (historical information, diagnosis, pathology report, etc.)
- Cohort B: Histologically diagnosed epithelial endometrial cancer (endometrioid adenocarcinoma; serous adenocarcinoma; undifferentiated carcinoma; mixed epithelial carcinoma; or adenocarcinoma not otherwise specified [N.O.S])
17. Relapsed and/or progressive disease
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
18. Fresh or archival tumor tissue samples must be provided to Sponsor for FolRα expression analysis as part of eligibility criteria for study entry and prior to study treatment
- FFPE blocks (preferably) or 10 unstained slides from the same block are required for study entry
- Cohort B (endometrial cancer): FolRα expression level which has been determined by central laboratory testing on pre-study fresh or archival tumor tissue is required for study eligibility and will be assessed during screening and must meet a minimum expression level of ≥ 1% tumor cell membrane staining of any intensity.
19. Evidence of measurable disease as defined by RECIST v1.1 (both cohorts)
Exclusion Criteria
1. Low-grade (grade 1) ovarian carcinoma (Expansion Cohort A [ovarian cancer] only)
2. Clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian carcinomas (Ovarian CohortA) and endometrial carcinosarcomas (malignant mixed Mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas (Endometrial Cohort B)
3. Prior treatment with a FolRa-targeting ADC (such as mirvetuximab; irrespective of warhead type) or with ADCs that contain a tubulin inhibitor (such as Mersana’s XMT-1536, which contains an auristatin derivative that inhibits tubulin polymerization)
4. Subjects who are platinum-refractory (no response or disease progression within 3 months of completion of therapy) during frontline treatment are excluded (Expansion Cohort A [ovarian cancer] only)
5. Greater than 3 lines of prior treatment (Expansion Cohort A [ovarian cancer] and Cohort B [endometrial cancer])
Study rules for evaluation of number of prior regimens:
• Adjuvant ± neoadjuvant is considered 1 line of therapy.
• Maintenance therapy (eg, bevacizumab and PARP inhibitors [PARPi]) will be considered as part of the preceding line of therapy (ie, not counted independently) if the patient achieves CR or PR and there was no clinical, biochemical or radiographic progression between completion of preceding regimen and the initiation of maintenance therapy.
• If one component of a multi-agent regimen is discontinued or changed due to toxicity in the absence of clinical, radiographic, or biochemical progression, the change will be considered as part of the preceding regimen (ie, not counted independently).
• If a regimen is stopped due to toxicity with documented absence of clinical, radiographic, or biochemical progression after 1 cycle, the regimen will not be counted as a separate line of therapy. If documentation is not available, discussion with sponsor is required prior to approval for enrollment.
• Radiation therapy will not be counted as a separate line of therapy.
• Hormonal therapy will not be counted as a separate line of therapy.
6. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment
7. Prior anticancer therapy (prior to first dose of study drug): chemotherapy within 3 weeks, PARPi within 2 weeks, other therapeutic anticancer antibodies within 3 weeks, radio- or toxin-immunoconjugates (eg, ADCs) within 10 weeks, or radiation therapy/ major surgery within 2 weeks of first dose of study drug.
8. Pre-existing clinically significant ocular disorders including, but not limited to: active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and /or monocular vision, keratitis, cataracts with significant visual impairment, uveitis, and Sjogren syndrome.
9. Previous solid organ transplantation
10. Sensory or motor neuropathy grade >1
11. Potentially fatal concurrent or recent malignancy. Subjects with past or current malignancy need to be discussed with the sponsor to determine eligibility. Examples of non-exclusionary malignancies include: cervical carcinoma Stage 1B or less; noninvasive basal cell and squamous cell skin carcinoma; localized malignant melanoma with a complete response of a duration of >10 years; low risk in situ breast cancer treated with curative intent; superficial noninvasive bladder cancer treated with curative intent.
12. Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis B or C
13. 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.
14. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from cycle 1 day 1 or the following at screening: congestive heart failure (New York Heart Association grade II or higher), left ventricular ejection fraction (LVEF) <45% at baseline, and clinically significant arrhythmia. Exceptions which are allowed are asymptomatic stable atrial arrythmias for ≥ 6 months prior to study enrollment with Sponsor approval. Extra systoles, or minor conduction abnormalities will be allowed.
15. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
16. History or clinical signs of meningeal or active central nervous system involvement
17. Known severe chronic obstructive pulmonary disease or asthma (defined as forced expiratory volume in 1 second (FEV1) <40% of expected), or active pneumonitis within 6 months of first day of study drug
18. History of significant cerebrovascular disease such as stroke
19. Known human immunodeficiency virus seropositivity
20. 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
21. Active hepatitis B or hepatitis C per Center for Disease Control guidelines 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 has undetectable viral DNA for 6 months prior to screening
22. Concurrent participation in another therapeutic treatment trial
23. Current signs/symptoms of bowel obstruction and/or signs/symptoms of bowel obstruction within 3 months of first day of study drug