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

NCT04478279 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ST101-101
• Study Type: interventional
• Target: 125
• Locations: 2 countries
• Sites: 11

Brief 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.

Conditions

Glioblastoma; Melanoma Stage IV; Breast Cancer; Prostate Cancer; GBM; Brain Cancer; Metastatic Breast Cancer; Metastatic Melanoma; Metastatic Prostate Cancer; Melanoma Recurrent; Prostate Cancer Metastatic; Recurrent Glioblastoma; Newly Diagnosed Glioblastoma; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT)

  Number of Participants with a Dose-Limiting Toxicity (DLT)

  20 months

• Adverse Events

  Number of Participants with at Least One Adverse Event, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)

  20 months

Secondary Outcomes (7)

• Area Under the Curve (AUC)

  30 Months

• Cmax

  20 months

• Terminal Half-Life (t1/2)

  20 months

• Overall Response

  20 months

• DCR

  20 Months

Study Arms (7)

Dose Escalation

EXPERIMENTAL

This cohort 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. ST101 will be administered intravenously (IV), initially once per week.

Drug: ST101

Dose Expansion HR+ Breast

EXPERIMENTAL

This cohort must have progressed after 1-2 hormone based therapies. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.

Drug: ST101

Dose Expansion Melanoma

EXPERIMENTAL

This cohort must have 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. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.

Drug: ST101

Dose Expansion GBM

EXPERIMENTAL

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. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.

Drug: ST101

Dose Expansion CRPC

EXPERIMENTAL

CRPC that has progressed after previous treatment with taxanes, abiraterone and enzalutamide/apalutamide. The starting dose of ST101 for Expansion will be derived from the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) and the best dosing schedule determined during Dose Escalation.

Drug: ST101

Dose Expansion Recurrent Glioblastoma

EXPERIMENTAL

Recurrent GBM patients must have completed radiation at least 3 months prior to minimize the inclusion of patients with pseudoprogression. Recurrent GBM patients must have unequivocal radiographic evidence of tumor progression by contrast-enhanced magnetic resonance imaging (MRI) scan within 21 days prior to registration. Patients must be able to delay surgery for 2 - 4 weeks per investigator decision

Drug: ST101

Newly Diagnosed Glioblastoma

EXPERIMENTAL

Newly diagnosed patients with a suboptimal resection or biopsy must be candidates for another surgical resection as determined by neurosurgical evaluation or multidisciplinary team based on the current standard of care that suggests that maximal safe resection is beneficial. Recurrent GBM patients must be candidates for tumor resection

Drug: ST101; Drug: Temozolomide; Radiation: Radiation

Interventions

ST101 DRUG

ST101 will be administered intravenously (IV), initially once per week with a flat dose on the schedule described for each study arm

Dose Escalation; Dose Expansion CRPC; Dose Expansion GBM; Dose Expansion HR+ Breast; Dose Expansion Melanoma; Dose Expansion Recurrent Glioblastoma; Newly Diagnosed Glioblastoma

Temozolomide DRUG

Temozolomide

Newly Diagnosed Glioblastoma

Radiation RADIATION

Radiation

Newly Diagnosed Glioblastoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.
• 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.
• 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.

You may not qualify if:

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• 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.
• Known hypersensitivity to ST101 or any of its excipients.
• Baseline corrected interval between q and t wave on electrocardiogram (ECG) (QTc) \> 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 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 infection requiring systemic therapy.
• 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

Sponsors & Collaborators

• Sapience Therapeutics: lead

Study Sites (11)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Northwestern Medicine Cancer Centers

Warrenville, Illinois, 60555, United States

Location

START Midwest

Grand Rapids, Michigan, 49503, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27708, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Edinburgh Cancer Centre

Edinburgh, EH4 2SP, United Kingdom

Location

The Beaston West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

University of Leeds

Leeds, LS9 7TF, United Kingdom

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

MeSH Terms

Conditions

Glioblastoma; Melanoma; Breast Neoplasms; Prostatic Neoplasms; Brain Neoplasms

Interventions

Temozolomide; Radiation

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Physical Phenomena

Study Officials

• Abi Vainstein-Haras, MD

  CMO

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.

Study Record Dates

• First Submitted: July 2, 2020
• First Posted: July 20, 2020
• Study Start: July 1, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); US (7)