Phase 1 trial to study the safety, pharmacokinetics and preliminary efficacy of STRO-002
given intravenously every 3 weeks.
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).
Inclusion Criteria:
1. Confirmation of diagnosis
2. Evidence of measureable disease as defined by RECIST 1.1
3. Age ≥ 18 years
4. ECOG performance status (0-1)
5. Life expectancy > 3 months
6. Toxicities related to prior therapy, such as peripheral neuropathy and arthralgias
must return to gr. 1 or less, except for alopecia, which can be gr. 2 or less at time
of enrollment
7. Adequate bone marrow, liver and renal functions
8. QTcF <500 msec
9. Ability to comply with treatment, PK and test schedules
10. Negative pregnancy test within 7 days and use a method of birth control
11. 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
12. Pathological confirmation of disease under study (historical information, diagnosis,
pathology report, etc)
a. Cohort A: High-grade serous EOC, fallopian tube cancer or primary peritoneal cancer
13. Relapsed and/or progressive disease
Cohort A (EOC):
- Platinum resistant and received 1-3 prior regimens or
- Progressed after 2 prior lines of platinum therapy (regardless of platinum
status) and received 2-3 prior regimens
14. 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
1. FFPE blocks (preferably) or 10 unstained slides from the same block are required
for study entry
2. Cohort A (EOC): FolRα expression is not required for eligibility and will be
assessed retrospectively post enrollment
Exclusion Criteria:
1. Low grade ovarian carcinoma (Grade 1).
2. Clear cell, mucinous and sarcomatous ovarian carcinomas.
3. Prior treatment with a FolRα-targeting ADCs or FolRα-targeting vaccines
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) History of severe allergic or anaphylactic reactions
to monoclonal antibody therapy or to antibody-related fusion protein treatment
5. Greater than 3 lines of prior treatment (Expansion Cohort A [ovarian cancer] only)
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, PARP inhibitor 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
8. Preexisting clinically significant ocular disorders including, but not limited to:
active or chronic corneal disorders, cataracts (except minor cataracts without
significant visual impairment which are allowed),, glaucoma, keratitis, retinopathy,
uveitis and Sjogrens syndrome. Myopia, "floaters", watering eyes are not exclusion
criteria
9. Previous solid organ transplantation
10. Sensory or motor neuropathy ≥ grade 2
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 C
13. Ongoing immunosuppressive therapy, including systemic corticosteroids. Note:
Physiologic replacement and use of topical or inhaled corticosteroids are allowed.
14. Clinically significant cardiac disease
15. Clinically significant pre-exisiting ocular disorders
16. Significant concurrent, uncontrolled medical condition
17. History or clinical signs of meningeal or active CNS involvement
18. Known severe chronic obstructive pulmonary disease or asthma
19. History of significant cerebrovascular disease
20. Known Human Immunodeficiency Virus seropositivity
21. Females who are pregnant or breastfeeding, and all women of child bearing potential
unwilling to use adequate barrier contraception while on treatment and for 16 weeks
after last dose
22. Positive serology for hepatitis B defined by a positive test for HBsAg
23. Concurrent participation in another therapeutic treatment trial
