A Phase 1-2 Study of ST101 in Patients With Advanced Solid Tumors

  • STATUS
    Recruiting
  • End date
    Jan 22, 2024
  • participants needed
    162
  • sponsor
    Sapience Therapeutics
Updated on 19 January 2022
cancer
sirolimus
carcinoma
metastasis
enzalutamide
cancer treatment
solid tumour
alopecia
oral contraception

Summary

This is an open-label, two-part, phase 1-2 dose-finding study designed to determine the safety, tolerability, PK, PD, and proof-of-concept efficacy of ST101 administered IV in patients with advanced solid tumors. The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.

Description

Dose escalation / regimen exploration phase During the dose escalation/regimen exploration phase, only patients diagnosed with locally advanced or metastatic melanoma, carcinoma or sarcoma of any tumor type who are refractory or intolerant to all available therapies that would impact survival will be enrolled.

ST101 will be administered intravenously (IV), initially once per week. The dose escalation cohorts will be recruited using a standard 3+3 design. At each new dosing cohort, there will be a 1-week observation period after dosing the first patient in order to assess safety prior to dosing the remainder of the patients in that cohort. The dose cohorts will be 0.5, 1, 2, 4, 8 and 16 mg/kg with once weekly (QW) dosing in all cohorts except for the highest dose level which will be dosed every other week (Q2W).

The expansion phase consists of 4 specific tumor-type cohorts, which each follow the same Simon 2-stage design. Fifteen (15) patients will be enrolled in each cohort and treated with the ST101 RP2D. If one or more responses is observed that cohort will be expanded to a total of 30 patients to further assess efficacy.

Responses will be graded using response evaluation criteria in solid tumors (RECIST) 1.1 (Eisenhauer 2009) for hormonal receptor positive (HRpos) locally advanced/metastatic breast cancer (LA/MBC) and melanoma, modified response assessment in neuro-oncology (RANO) (Ellingson 2017) for GBM and prostate cancer clinical trials working group 3 (PCWG3) (Scher 2016) for castration-resistant prostate cancer (CRPC).During the expansion phase, only patients diagnosed with the following tumor types will be allowed into this phase of the

study
  • HRpos LA/MBC that has 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.
  • Melanoma that has progressed after/or on treatment with an immune checkpoint inhibitor (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.
  • Primary (de novo) GBM that has recurred or progressed (per modified RANO criteria) after 1 standard treatment regimen. Standard therapy is defined as maximal surgical resection, radiotherapy, and concomitant temozolomide with radiotherapy or adjuvant chemotherapy with temozolomide. Patients that undergo tumor treating fields as an adjuvant to first line therapy are allowed.
  • CRPC that has progressed after previous treatment with taxanes, abiraterone and enzalutamide/apalutamide.

The tumor types in the expansion phase may change based on emerging data from the dose escalation phase of this study. Additional mini cohorts of 10 patients may be added to the expansion phase based on efficacy signals during the dose escalation phase.

Details
Condition Advanced Solid Tumor
Treatment ST101
Clinical Study IdentifierNCT04478279
SponsorSapience Therapeutics
Last Modified on19 January 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Inclusion Criteria
Able and willing to sign informed consent form (ICF) and comply with the protocol and the restrictions and assessments therein
Male or female ≥18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Must have a locally advanced or metastatic inoperable tumor as follows
For the dose escalation/regimen exploration phase: melanoma, carcinoma, or sarcoma
For the expansion phase: HR positive LA/MBC, melanoma, GBM, CRPC
Agrees to provide a newly obtained biopsy of an accessible lesion (if they can be
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
biopsied based on the investigator's assessment) prior to the start of study
therapies
treatment, and to repeat biopsy once during study treatment. Tissue obtained
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
for the biopsy must not be previously irradiated (unless progressing following
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
irradiation), but a new or progressing lesion in the radiation field is
acceptable. Archived biopsies are acceptable for GBM patients
iv. CRPC that has progressed after previous treatment with taxanes, abiraterone
and enzalutamide/apalutamide or that are intolerant to these treatments
Evaluable disease per RECIST 1.1, modified RANO or PCWG3 with at least one target
lesion
Disease that progressed on, or is non-responsive to, the previous line of therapy
per RECIST 1.1, modified RANO or PCWG3
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
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

Known hypersensitivity to ST101 or any of its excipients
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
Baseline corrected interval between q and t wave on electrocardiogram (ECG) (QTc)
Active infection requiring systemic therapy
> 480 msec using Fredericia's formula
Symptomatic ascites or pleural effusion. A patient who is clinically stable
following treatment for these conditions (including therapeutic thoraco- or
paracentesis) is eligible
Known active central nervous system (CNS) metastases and/or carcinomatous
Exclusion Criteria for GBM Cohort
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
Presence of any other active malignancy requiring systemic therapy other than the
disease under study
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
Active infection with hepatitis B or hepatitis C, defined by a detectable viral
load. Testing is not required for eligibility
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
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
Active immune thrombocytopenic purpura or other chronic thrombocytopenic
condition
Therapeutic anticoagulation that cannot be interrupted for a biopsy or had a
thromboembolic event within the last 6 months
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
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
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
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