Inclusion Criteria:
1. Able and willing to sign informed consent form (ICF) and comply with the
protocol and the restrictions and assessments therein.
2. Male or female ≥18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
4. Must have a locally advanced or metastatic inoperable tumor as follows:
1. For the dose escalation/regimen exploration phase: melanoma, carcinoma, or
sarcoma. 2. For the expansion phase: HR positive LA/MBC, melanoma, GBM, CRPC. 5. Agrees to provide a newly obtained biopsy of an accessible lesion (if they can
be biopsied based on the investigator's assessment) prior to the start of study
treatment, and to repeat biopsy once during study treatment. Tissue obtained
for the biopsy must not be previously irradiated (unless progressing following
irradiation), but a new or progressing lesion in the radiation field is
acceptable. Archived biopsies are acceptable for GBM patients.
6. In the investigator's opinion, the patient may not derive clinical benefit
from, or is ineligible for, a particular form of standard therapy on medical
grounds, or the patient failed or did not tolerate one or more of other
anti-cancer therapies:
a. For the dose escalation/regimen exploration phase up to 3 previous lines of
systemic anticancer therapies are allowed. Since this is a FIH study, it's
important that patients are not refractory to therapeutic intervention due to
multiple lines of prior therapies.
a. For the expansion phase: i. HRpos LA/MBC must have progressed after prior
1-2 hormone-based therapies. Previous treatment with cyclin-dependent kinase
4/6 (CDK4/6) inhibitor, mammalian target of rapamycin (mTOR) inhibitor or
chemotherapy is allowed as monotherapy or in combination ii. Melanoma that has
progressed after or on treatment with a CPI and have received 1-2 prior lines
of therapy for their advanced/metastatic disease. Patients that have BRAF
mutated disease should also have received one line of appropriate targeted
therapy iii. Primary (de novo) GBM that has recurred or progressed (per
modified RANO criteria) after 1 standard treatment regimen (surgery,
radiotherapy, and temozolomide therapy). Patients that undergo tumor treating
fields as an adjuvant to first line therapy are allowed.
iv. CRPC that has progressed after previous treatment with taxanes, abiraterone
and enzalutamide/apalutamide or that are intolerant to these treatments.
7. Evaluable disease per RECIST 1.1, modified RANO or PCWG3 with at least one
target lesion. 8. Disease that progressed on, or is non-responsive to, the previous line of
therapy per RECIST 1.1, modified RANO or PCWG3.
9. If not menopausal or surgically sterile, willing to practice at least one of
the following highly effective methods of birth control for at least a
(partner's) menstrual cycle before and for four months after ST101
administration:
- (1) total abstinence from sexual intercourse with a member of
the opposite sex; (2) sexual intercourse with vasectomized male/sterilized
female partner; (3) combined (estrogen and progestogen containing) or
progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, parenteral, transvaginal or transdermal) for at least 3 consecutive
months prior to investigational product administration; (4) other acceptable
forms of birth control (condoms, contraceptive sponge, diaphragm or vaginal
ring with spermicide or cream); (5) use of an intrauterine contraceptive
device.
10. All previous anti-cancer therapy-related adverse events should have resolved to
grade 1 or baseline value with the exception of alopecia. Levothyroxine is
allowed for patients that previously received a CPI and experienced thyroid
dysfunction.
Exclusion Criteria.
1. Use of small molecule or tyrosine kinase inhibitor within 2 weeks or 5
half-lives (whichever is shorter) prior to the first dose of study drug;
chemotherapy, investigational drug or biological cancer therapy within 3 weeks
prior to the first dose of study therapy; nitrosourea or radioisotope within 6
weeks prior to first dose.
2. Known hypersensitivity to ST101 or any of its excipients.
3. Baseline corrected interval between q and t wave on electrocardiogram (ECG)
(QTc) > 480 msec using Fredericia's formula.
4. Symptomatic ascites or pleural effusion. A patient who is clinically stable
following treatment for these conditions (including therapeutic thoraco- or
paracentesis) is eligible.
5. Known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate
provided they are clinically stable for at least 4 weeks prior to study entry,
have no evidence of new or enlarging brain metastases, and are off steroids for
at least 14 days prior to first dose of study drug. This criterion does not
apply to patients on the GBM cohort.
6. Presence of any other active malignancy requiring systemic therapy other than
the disease under study.
7. Active infection with human immunodeficiency virus (HIV) and CD4+ T-cell count
<350/μL. Patients not on established ART for at least four weeks and having a
detectable HIV viral load. Testing is not required for eligibility.
8. Active infection with hepatitis B or hepatitis C, defined by a detectable viral
load. Testing is not required for eligibility.
9. Active autoimmune disease or a documented history of autoimmune disease or
syndrome that requires systemic steroids or immunosuppressive agents. Vitiligo
or resolved childhood asthma/atopy are exceptions to this rule. Patients
requiring intermittent use of bronchodilators or topical steroids would not be
excluded from the study. Patients with hypothyroidism that is stable on hormone
replacement or controlled type 1 diabetes will not be excluded from the study.
10. Use of systemic corticosteroids to treat inflammatory or autoimmune symptoms
within 15 days or other immunosuppressive drugs within 30 days prior to the
start of the study. Inhaled and topical corticosteroids are permitted. Up to 10
mg/day prednisone or equivalent is permitted as replacement therapy for adrenal
insufficiency only.
11. Active infection requiring systemic therapy.
12. Active immune thrombocytopenic purpura or other chronic thrombocytopenic
condition.
13. Therapeutic anticoagulation that cannot be interrupted for a biopsy or had a
thromboembolic event within the last 6 months.
14. History or clinical evidence of any surgical or medical condition which the
investigator judges as likely to interfere with the results of the study or
pose an additional risk in participating, or makes the patient unlikely to
comply with the study related visits and assessments particularly any
pre-existing condition that would put the patient at additional risk should
they experience an infusion-related reaction, e.g., rapidly progressive or
uncontrolled disease involving a major organ system
- - vascular, cardiac,
pulmonary, gastrointestinal, gynecologic, hematologic, neurologic, neoplastic,
renal, endocrine, or an immunodeficiency.
15. Unable to comply with the visits and requirements of the protocol due to
psychiatric condition or substance abuse. Pregnant or breastfeeding or planning
to conceive or father children within the projected duration of the study.
16. Exclusion Criteria for GBM Cohort:
a) Any prior therapy for GBM other than that which is considered SOC for
primary GBM, including but not limited to the following: i. more than one line
of adjuvant temozolomide ii. prior treatment with another investigational drug
iii. prior treatment with bevacizumab (Avastin) or other vascular-endothelial
growth factor (VEGF) inhibitors or VEGF-receptor signaling inhibitors iv. prior
treatment with nitrosoureas v. prior therapy that included interstitial
brachytherapy or Gliadel® Wafers (carmustine implants) b) secondary GBM (i.e.,
GBM that progressed from low-grade diffuse astrocytoma or AA) c) tumor with a
clinically significant mass effect (>5 mm midline shift) while on a stable
corticosteroid dose d) prednisone or equivalent dose of >10mg per day e) known
history of allergy
