ST101 for Advanced Cancer

Not currently recruiting at 10 trial locations

Overseen By Steve Kaesshaefer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sapience Therapeutics

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Active infection, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the best dose and assess the safety and effectiveness of a new drug, ST101, for individuals with advanced solid tumors. It targets various cancers, including melanoma or breast cancer that has worsened after specific treatments, and recurrent or newly diagnosed glioblastoma (a type of brain cancer). The trial seeks participants whose cancer has not responded to or who cannot use standard treatments. Participants should have a tumor that cannot be surgically removed and must be willing to undergo new biopsies.

As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting the study. Specifically, you must not use small molecule or tyrosine kinase inhibitors within 2 weeks or 5 half-lives before the first dose, and chemotherapy or biological cancer therapy within 3 weeks prior. If you're on systemic corticosteroids or immunosuppressive drugs, you need to stop them 15 to 30 days before starting the study, except for certain exceptions like inhaled or topical corticosteroids.

Is there any evidence suggesting that ST101 is likely to be safe for humans?

Research has shown that ST101 has been safe in earlier studies. Patients with recurring glioblastoma (GBM) who received ST101 experienced outcomes similar to current treatments while maintaining a strong safety record, indicating the treatment is generally well-tolerated. In another study, a patient with skin cancer (melanoma) showed partial improvement lasting over 51 weeks, suggesting the treatment might be effective and manageable.

Since this trial is in its early stages, it is important to note that the initial phases often focus on determining the right dosage. While ST101 appears promising in terms of safety, researchers will continue to monitor its safety across different types of advanced cancers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ST101 because it offers a new approach for treating advanced cancers like metastatic melanoma, glioblastomas, and hormone receptor-positive breast cancer. Unlike existing treatments such as immune checkpoint inhibitors or hormone therapies, ST101 is designed to target specific pathways involved in cancer cell survival and proliferation, potentially overcoming resistance to current therapies. This unique mechanism of action could provide new hope for patients whose cancers have progressed despite using all standard treatment options. Additionally, ST101 is administered intravenously, which allows for precise dosing and monitoring, possibly enhancing treatment effectiveness while minimizing side effects.

What evidence suggests that this trial's treatment, ST101, could be effective for advanced cancer?

Studies have shown that ST101, a compound targeting a protein linked to tumors, can aid patients with certain advanced cancers. This trial evaluates ST101 across various treatment arms for different cancer types, including cutaneous melanoma, recurrent glioblastoma, and hormone receptor-positive breast cancer. One study reported a partial response in a patient with cutaneous melanoma, with the tumor shrinking and this improvement lasting over 51 weeks. Early results suggest that ST101 may be effective on hard-to-treat solid tumors. The compound has received fast track status for recurrent glioblastoma, a challenging brain cancer, highlighting its potential. These findings indicate that ST101 could be a helpful treatment for advanced cancers, but further research is needed to confirm its benefits. ^{1 2 3 6 7}

Who Is on the Research Team?

Abi Vainstein-Haras, MD

Principal Investigator

CMO

Are You a Good Fit for This Trial?

Adults with advanced solid tumors, including glioblastoma and certain types of breast, prostate, and melanoma cancers. Participants must have a measurable disease that's progressed after previous treatments, be willing to use birth control if necessary, and able to provide biopsy samples. They should not have other active cancers or infections like hepatitis B/C or HIV, nor should they be on certain medications that could affect the trial.

Inclusion Criteria

I agree to have two biopsies: one before and one during the study.

All my side effects from cancer treatment have improved, except for hair loss.

My tumor cannot be removed by surgery and has spread.

Exclusion Criteria

I have HIV with a CD4+ T-cell count below 350.

Unable to comply with the visits and requirements of the protocol due to psychiatric condition or substance abuse

I have fluid buildup in my abdomen or around my lungs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

ST101 is administered intravenously in a dose-escalation phase to determine safety and tolerability. Dosing starts once per week with a 1-week observation period for safety assessment.

20 months

Weekly visits for dosing and observation

Dose Expansion

Participants are treated with the recommended phase 2 dose (RP2D) of ST101 in specific tumor-type cohorts to assess efficacy.

20 months

Regular visits for treatment and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ST101

Trial Overview The study is testing ST101 given intravenously alongside Temozolomide and Radiation in two phases: first to find the safest dose (Phase 1) and then to see how well it works at that dose (Phase 2). Researchers want to learn about its safety, how the body processes it, and its preliminary effectiveness against cancer.

How Is the Trial Designed?

Group I: Newly Diagnosed Glioblastoma Experimental Treatment 3 Interventions

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

Group II: Dose Expansion Recurrent Glioblastoma Experimental Treatment 1 Intervention

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

Group III: Dose Expansion Melanoma Experimental Treatment 1 Intervention

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.

Group IV: Dose Expansion HR+ Breast Experimental Treatment 1 Intervention

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.

Group V: Dose Expansion GBM Experimental Treatment 1 Intervention

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.

Group VI: Dose Expansion CRPC Experimental Treatment 1 Intervention

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.

Group VII: Dose Escalation Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Sapience Therapeutics

Lead Sponsor

Trials

2

Recruited

260+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04478279

NCT04478279 | A Phase 1-2 Study of ST101 in Patients ... 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 ...

2. sapiencetherapeutics.com sapiencetherapeutics.com/sapience-therapeutics-presents-phase-1-data-at-asco-2022-including-efficacy-proof-of-concept-with-st101-in-patients-with-refractory-solid-tumors/

News & Events Treatment with ST101 resulted in 1 confirmed partial response (PR) in a patient with cutaneous melanoma lasting more than 51 weeks and 2 patients with ongoing ...

3. aacrjournals.org aacrjournals.org/mct/article/20/12_Supplement/P06-03/675875/Abstract-P06-03-ST101-a-peptide-targeting

Abstract P06-03: ST101, a peptide targeting oncogenic ... ST101, a peptide targeting oncogenic transcription factor C/EBPβ: initial safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) data ...

4. targetedonc.com targetedonc.com/view/response-to-st101-in-refractory-solid-tumors-leads-to-expansion-of-phase-2-arm

Response to ST101 in Refractory Solid Tumors Leads ... Interim clinical data from a phase 1/2 clinical trial of ST101 in refractory solid tumors leads to the expansion of the phase 2 glioblastoma arm of the study.

5. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-st101-for-recurrent-glioblastoma

FDA Grants Fast Track Designation to ST101 for Recurrent ... The FDA has granted a fast track designation to ST101, a peptide antagonist of C/EBPβ, for the treatment of patients with recurrent glioblastoma.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2011

Efficacy and biomarker analysis of phase 2 (P2) ... Monotherapy ST101 in pts with rGBM has an excellent safety profile and results in comparable outcomes to current 2 nd line treatments.

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-06735

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