ST316 for Advanced Cancers

Recruiting at 10 trial locations

Overseen By Joyce Gakuria

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sapience Therapeutics

Must not be taking: Steroids, Anti-arrhythmics

Disqualifiers: CNS metastases, Cardiac disease, Hypertension, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called ST316 for individuals with advanced solid tumors, including cancers that may involve the WNT/β-catenin signaling pathway. Researchers will explore using ST316 alone or with other treatments, focusing on colorectal cancer (CRC). Ideal candidates have advanced cancers unresponsive to standard treatments and colorectal cancer that has worsened after previous therapies. Participants must be willing to undergo biopsies to provide tissue samples for analysis. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that participants should not have hypersensitivity to certain drugs used in the trial, like bevacizumab or irinotecan, which might imply some restrictions. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ST316, a new cancer treatment, appears safe. In earlier studies, patients with advanced solid tumors tolerated ST316 well. Reports highlight its safety and early effectiveness in blocking a specific cancer pathway called Wnt/β-catenin.

When combined with other treatments like FOLFIRI and bevacizumab, it remains safe. FOLFIRI with bevacizumab, often used for colorectal cancer, typically has manageable side effects.

For the combination of ST316 with Lonsurf and bevacizumab, common side effects of Lonsurf include low blood counts and tiredness, which are generally manageable. Lastly, when combined with fruquintinib, the side effects remain manageable and do not increase the risk of serious problems.

Overall, although the trial is in an early stage, the data so far suggests that ST316 and its combinations are generally safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ST316 for advanced colorectal cancer because it offers a novel approach to tackling this challenging disease. Unlike the standard care options, like FOLFIRI and bevacizumab, ST316 may have a unique mechanism of action that could enhance the effectiveness of existing therapies. Specifically, ST316 is being explored in combination with treatments such as FOLFIRI, bevacizumab, Lonsurf, and fruquintinib, potentially boosting their efficacy. This new combination strategy aims to improve patient outcomes by exploiting ST316's potential benefits, giving hope for more effective treatment options in colorectal cancer.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research has shown that ST316 is designed to block the Wnt/β-catenin signaling pathway, which is often overly active in cancers such as colorectal cancer. This pathway plays a crucial role in cancer cell growth, so inhibiting it might help slow or stop tumors. In this trial, participants may receive ST316 alone or with other treatments. Early results suggest that ST316 can be effective on its own and might perform even better when combined with treatments like FOLFIRI, Lonsurf, or Fruquintinib, which have shown promise in treating colorectal cancer. For instance, using Lonsurf with bevacizumab has helped patients live longer. Similarly, Fruquintinib improved survival for those with advanced colorectal cancer. These combinations aim to enhance treatment effectiveness by attacking the cancer in different ways. ^{1 3 4 6 7}

Who Is on the Research Team?

Abi Vainstein-Haras

Principal Investigator

CMO

Are You a Good Fit for This Trial?

Adults (≥18 years) with various advanced solid tumors that are inoperable or have spread, and who haven't benefited from standard treatments or can't tolerate them. Participants must be able to provide tumor tissue samples, practice effective birth control if applicable, and have a performance status indicating they are relatively active.

Inclusion Criteria

My doctor thinks standard treatments won't work for me or I've had bad reactions to cancer treatments.

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

I am fully active or can carry out light work.

Exclusion Criteria

Your heart's electrical activity (ECG) shows a prolonged QT interval.

You have been diagnosed with HIV.

I am not currently receiving any cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1 dose escalation/regimen exploration to determine safety, tolerability, PK, and PD of ST316

Varies by cohort

Expansion

Phase 2 expansion to evaluate proof-of-concept efficacy of ST316 in combination or monotherapy

3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• ST316

Trial Overview ST316 is being tested for safety and effectiveness against certain cancers likely affected by WNT/β-catenin pathway abnormalities. The trial has two parts: first to find the right dose of ST316, then to see how well it works at that dose.

How Is the Trial Designed?

Group I: ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase Experimental Treatment 1 Intervention

ST316 Monotherapy Colon Rectal Cancer (CRC) Expansion phase n=15-30

Group II: ST316 & Lonsurf + Bevacizumab Combination CRC Expansion phase Experimental Treatment 2 Interventions

ST316 \& Lonsurf \& bevacizumab n=15-30

Group III: ST316 & Fruquintinib Combination CRC Expansion phase Experimental Treatment 2 Interventions

ST316 \& Fruquintinib Combination CRC Expansion phase n=15-30

Group IV: ST316 & FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase Experimental Treatment 2 Interventions

ST316 \& FOLFIRI/Bevacizumab Combination Colon Rectal Cancer (CRC) Expansion phase Expansion phase n=15-30

Group V: Dose Escalation Phase Experimental Treatment 1 Intervention

The dose cohorts will be 0.5, 1, 2, 4, 8 \& 12 mg/kg IV once weekly (QW)

ST316 is already approved in United States for the following indications:

Approved in United States as ST316 for:

• Familial adenomatous polyposis (FAP) - Orphan Drug Designation

Who Is Running the Clinical Trial?

Sapience Therapeutics

Lead Sponsor

Trials

2

Recruited

260+

Published Research Related to This Trial

Sunitinib is an effective treatment for patients with gastrointestinal stromal tumors (GIST) who are resistant to imatinib, showing a response rate of 27.1% and a disease control rate of 70.8% over a median follow-up of 89 weeks.

Patients with exon 9 mutations had a significantly better overall survival compared to those with exon 11 mutations, and the 37.5 mg continuous daily dose of sunitinib was associated with fewer adverse effects compared to the 50 mg/d (4/2) regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of sunitinib on patients with imatinib-resistant gastrointestinal stromal tumor]. Liu, X., Jiang, WZ., Guan, GX., et al.[2022]

A systematic review of 128 randomized clinical trials involving 47,432 patients showed that anticancer drugs provided a statistically significant benefit in progression-free survival (PFS) and overall survival (OS) compared to best supportive care, with hazard ratios of 0.58 and 0.82, respectively.

Despite these benefits, the absolute gains in survival were modest, with PFS extending by only 2.1 months and OS by 0.5 months, and there was a weak correlation between severe toxicity and treatment efficacy, indicating that higher toxicity did not necessarily lead to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and benefits of anticancer drugs in advanced cancer patients: A systematic review and meta-analysis. Moreau Bachelard, C., Coquan, E., du Rusquec, P., et al.[2022]

PARP inhibitors showed significantly better progression-free survival (PFS) compared to other maintenance therapies for advanced ovarian cancer, with hazard ratios ranging from 0.59 to 0.68 based on 16 trials.

Overall survival (OS) data for these therapies are still immature, indicating that while PFS is promising, more research is needed to fully understand long-term outcomes and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic literature review of efficacy and safety of first-line maintenance therapy trials in advanced ovarian cancer. Guy, H., Hawkes, C., Walder, L., et al.[2022]

In a study of 470 Japanese patients with imatinib-resistant or intolerant gastrointestinal stromal tumors, sunitinib demonstrated good efficacy with a 20% objective response rate and a median progression-free survival of 22.4 weeks.

The treatment was generally well-tolerated, with 70% of patients experiencing grade ≥ 3 adverse events, but specific early adverse events like hand-foot syndrome and leukopenia were linked to improved progression-free survival, indicating they may serve as positive prognostic markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor. Komatsu, Y., Ohki, E., Ueno, N., et al.[2022]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05848739

Study Details | NCT05848739 | A Phase 1-2 of ST316 With ... This is an open-label, two-part, phase 1-2 study designed to determine the safety, tolerability, PK, pharmacodynamics (PD), and proof-of-concept efficacy of ST ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4022139/

FOLFIRI® and Bevacizumab in first-line treatment for ... Over 50% of colorectal cancer (CRC) patients develop metastases. The aim of this study was to evaluate efficacy and tolerance of first-line FOLFIRI® + ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10832121/

Effectiveness of bevacizumab in the treatment of metastatic ... The addition of BEV can enhance the anti-tumor ability and disease control, while cetuximab and panitumumab may have stronger ability.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/408055

A Phase 1-2 of ST316 With Selected Advanced ... This is an open-label, two-part, phase 1-2 study designed to determine the safety, tolerability, PK, pharmacodynamics (PD), ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1552914/full

Advances in bevacizumab in colorectal cancer A meta-analysis demonstrated that mCRC patients with primary tumor resection (PTR) have better survival when managed with bevacizumab (3). Yet, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2990582/

A retrospective observational study on the safety and ... The objective of the present retrospective observational study is to analyse the response and toxicity of first-line treatment with FOLFIRI+ ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01270438

Combination Chemotherapy and Bevacizumab With or ... This phase II clinical trial is studying how well giving combination chemotherapy and bevacizumab with or without RO4929097 works in treating patients with ...