STRO+bev 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 carried out.
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. High Grade serous epithelial ovarian cancer (EOC), fallopian tube or primary peritoneal cancer with pathology report documentation of tumor type.
6. At least one radiographically measurable (Target) lesion per RECIST v1.1.
7. Pathologic tissue (slides or tissue block) that meets protocol specifications and is
sent to central laboratory for FolRα expression testing prior to enrollment.
a. For the dose escalation part of the study, tissue may be from either archival tumor tissue or from a biopsy performed during screening.
b. For dose expansion part of the study, tissue from both archival tumor tissue and a biopsy performed during screening is required. If archival tumor tissue is not available or there is inadequate tissue for central laboratory analysis, the subject may be enrolled in the study with Sponsor (or designee) approval.
8. Adequate bone marrow function defined as:
a. 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)
b. Hemoglobin ≥ 9g/dL (use of growth factors or transfusion to achieve this
level is NOT permitted within 3 weeks of first dose of study drug)
c. Platelet count ≥ 100 x 103/μL (transfusion to achieve this level is NOT
permitted within 3 weeks of first dose of study drug)
9. Adequate liver function defined as:
a. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <
2.5 times the upper limit of normal (ULN)
b. Alkaline phosphatase (ALP) < 2.5 x ULN
c. Bilirubin < 1.5 x ULN
10. Adequate renal function defined as serum creatinine ≤ 1.5 x ULN or creatinine
clearance (CrCl) > 40 mL/min (Cockcroft-Gault equation or 24-hour urine
assessment).
11. Calculated QT interval corrected for heart rate using Fridericia correction formula
(QTcF), screening electrocardiogram (ECG) and C1D1 pre-dose ECG must be < 500
msec.
12. Ability to comply with treatment, PK and testing schedules.
13. 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/bevacizumab and 6 months after the last dose of bevacizumab.
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 post-menopausal 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 (e.g., hormonal therapy, prior chemotherapy).
Subjects enrolling into Dose Escalation must also meet the following inclusion criteria:
14. Relapsed and/or PD on last treatment regimen and one of the following:
a. Primary Platinum refractory (no response or progression within 3 months of
last dose of platinum-based therapy) and received no more than 1 prior
regimen
b. Primary platinum resistant (response duration to platinum therapy of 3-6
months after last dose of platinum therapy) and received no more than 4
prior regimens
c. Platinum sensitive (response duration of 6 months or longer from last dose
of platinum therapy) 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
Study rules for evaluation of number of prior regimens:
• Adjuvant ± neoadjuvant is considered 1 line of therapy.
• Maintenance therapy (e.g, bevacizumab, PARP inhibitors [PARPi]) will be
considered as part of the preceding line of therapy (i.e,, not counted
independently) if the subject 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 (i.e,, 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.
• Radiation therapy will not be counted as a separate line of therapy.
• Hormonal therapy 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.
Subjects enrolling into Part 2, Dose Expansion must also meet the following inclusion
criteria:
15. Relapsed and/or PD on last treatment regimen and one of the following:
a. Platinum resistant (response duration to platinum therapy of 3-6 months
after last dose of platinum therapy) and received no more than 4 prior
regimens
b. Platinum sensitive (response duration of 6 months or longer from last dose
of platinum therapy) 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
1. Low grade ovarian carcinoma (Grade 1).
2. Clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian
carcinomas, endometrial leiomyosarcoma, and endometrial stromal sarcomas.
3. Prior treatment with an ADC with a warhead that is a tubulin inhibitor (such as
Immunogen’s mirvetuximab, Esai’s MORAb-202, and Mersana’s XMT-1536).
4. Prior treatment with other FolRα targeting agents unless approved by a Sutro medical
monitor or designee.
5. Subjects who are primary platinum-refractory (no response or disease progression
within 3 months of completion of therapy) during frontline treatment are excluded from
the Expansion Cohort (Allowed in Dose Escalation if no more than 1 prior regimen was
received).
6. Greater than 4 prior lines of treatment (> 1 prior if primary platinum refractory).
7. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy,
antibody-related fusion protein treatment, or bevacizumab.
8. Any prior toxicity that required permanent discontinuation of bevacizumab or other
contraindication to receive bevacizumab per institutional guidelines (e.g., rectosigmoid
involvement).
9. Prior anti-cancer therapy (prior to 1st dose of study drug) that meet the following
criteria: chemotherapy within 3 weeks, PARPi within 2 weeks, other therapeutic anticancer
antibodies within 3 weeks, radio- or toxin-immunoconjugates (e.g., ADCs)
within 10 weeks, or radiation therapy/ surgery within 4 weeks.
10. 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
11. Hemoptysis within 3 months of initiation of study treatment.
12. Nephrotic syndrome within 3 months of initiation of study treatment. If subject has
proteinuria at screening per urine dipstick test ≥ 2+, must have a 24-hour urine
collection and testing for protein. Excluded for > 2 gm of protein per 24 hours.
13. Bleeding requiring transfusion within 3 months of initiation of study treatment.
14. Previous solid organ transplantation.
15. Current signs/symptoms of bowel obstruction and/or signs/symptoms of or bowel
obstruction within 3 months of initiation of study treatment.
16. History of GI perforation or symptoms of recent bowel obstruction. Subjects with a
history of abdominal fistula will be considered eligible if the fistula was surgically
repaired or has healed, there has been no evidence of fistula for at least 6 months, and
subject is deemed to be at low risk of recurrent fistula.
17. Residual Common Technical Criteria for Adverse Events (CTCAE) ≥ Grade 2 toxicity
from prior anticancer therapy with the exception of Grade 2 alopecia or Grade 2
neuropathy.
18. Uncontrolled hypertension (blood pressure ≥ 160/100; must be controlled prior to study
entry).
19. Sensory or motor neuropathy > Grade 1 at screening prior to initiation of study
treatment.
20. Potentially fatal concurrent or recent malignancy. Subjects with past or current
malignancy need to be discussed with the sponsor to determine eligibility. Examples on
non-exclusionary malignancies include:
Cervical carcinoma Stage 1B or less; Non-invasive basal cell and squamous cell
skin carcinoma; Localized malignant melanoma with a complete response
duration of > 10 years; Low risk in situ breast cancer treated with curative intent
and no evidence of disease; Superficial non-invasive bladder cancer treated with
curative intent.
21. Chronic or ongoing active infectious disease requiring systemic treatment such as, but
not limited to, chronic renal infection, chronic chest infection with bronchiectasis, and
tuberculosis.
22. 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.
23. 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.
24. History or clinical signs of meningeal or active central nervous system involvement.
25. Known severe chronic obstructive pulmonary disease or asthma defined as forced expiratory volume in one second (FEV1) < 40% of expected, and active pneumonitis within 6 months of initiation of study treatment.
26. History of stroke or history of significant cerebrovascular disease (i.e., transient ischemic attack) within 6 months of initiation of study treatment.
27. History of pulmonary embolism or any Grade 3 thromboembolic event within 6 months of initiation of study treatment.
28. Known human immunodeficiency virus seropositivity.
29. 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:
a. Subject has had HCV but received antiviral treatment and shows no detectible HCV viral DNA for 6 months prior to screening
b. Subject has had HBV but is HBV surface antigen (HBsAg) and viral DNA negative at screening
c. Subject has had HBV but received antiviral treatment and have undetectable viral DNA for 6 months prior to screening
30. Concurrent participation in another therapeutic treatment trial
31. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
32. 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