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

Trial Summary

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.

What safety data exists for anticancer drugs in advanced cancer patients?

Anticancer drugs in advanced cancer patients have shown some benefits, but they also come with risks of severe side effects, including serious and fatal adverse events. Molecular target anticancer drugs, in particular, have been associated with an increased risk of serious and fatal adverse events compared to placebo. ^{1 2 3 4 5}

What is the purpose of this trial?

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 ST316 administered IV in subjects with selected advanced solid tumors likely to harbor abnormalities of the WNT/β-catenin signaling pathway. The study consists of two phases: a phase 1 dose escalation/regimen exploration phase and a phase 2 expansion phase.

Research Team

Abi Vainstein-Haras

Principal Investigator

CMO

Eligibility Criteria

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.

I am not currently receiving any cancer treatments.

You have been diagnosed with HIV.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Risks and benefits of anticancer drugs in advanced cancer patients: A systematic review and meta-analysis. [2022]

2. India 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. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Systematic literature review of efficacy and safety of first-line maintenance therapy trials in advanced ovarian cancer. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of sunitinib on patients with imatinib-resistant gastrointestinal stromal tumor]. [2022]

5. England 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. [2022]