Oral TACH101 for Cancer

Not currently recruiting at 8 trial locations

Overseen By Chan Chandhasin, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tachyon Therapeutics, Inc.

Must not be taking: Anticancer therapy

Disqualifiers: Brain metastases, Cardiovascular disease, 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 tests a new oral treatment called TACH101 for individuals with advanced or metastatic solid tumors that have not responded well to other treatments. The first part of the trial aims to find the right dose and identify any side effects. The second part evaluates the treatment's effectiveness, particularly for specific types of gastrointestinal cancers or colorectal cancer with high microsatellite instability. Individuals with solid tumors unresponsive to standard treatments might be suitable candidates for this trial. 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 any ongoing anticancer therapy at least 4 weeks or 5 half-lives before the first dose. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that TACH101 is likely to be safe for humans?

Research has shown that TACH101 was well tolerated in earlier studies. Patients with advanced cancer who tried this treatment found it manageable, even after receiving other treatments. Some promising signs of benefits appeared in these patients.

TACH101 targets specific proteins related to cancer, demonstrating strong anti-cancer effects in lab tests. Although this is an early study, the goal is to find the right dose that balances effectiveness and safety. As a Phase 1 trial, the primary aim is to understand the treatment's safety in people. Safety data from this phase will help adjust dosing and reduce side effects as the study progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

TACH101 is unique because it offers a fresh approach to treating certain cancers, specifically targeting the enzyme KAT6A, which plays a role in cancer cell growth. Unlike many standard treatments that focus on broadly attacking cancer cells with chemotherapy, TACH101's mechanism aims to selectively inhibit this enzyme, potentially reducing side effects and improving effectiveness for cancers with high microsatellite instability and specific gastrointestinal cancers. Researchers are excited about TACH101 because it represents a new class of treatment that could provide more tailored and effective options for patients with these challenging types of cancer.

What evidence suggests that TACH101 might be an effective treatment for cancer?

Research has shown that TACH101 might help people with advanced cancer. In this trial, participants will receive TACH101 in two phases. Phase 1a involves a dose escalation to determine the optimal dosing regimen. Phase 1b will expand on this by administering TACH101 at the recommended dose to two cohorts: participants with gastrointestinal cancers and those with high microsatellite instability (MSI-H) metastatic colorectal cancer. TACH101 blocks a protein called KDM4, which aids cancer cell growth, making it a promising option for treating different types of cancer. Early results suggest it could be effective for certain stomach and colon cancers, especially those with high microsatellite instability. While more research is needed, the initial findings offer hope for people with these conditions. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including gastrointestinal cancers and MSI-H colorectal cancer that didn't respond to standard treatments. Participants must have measurable disease, be in good physical condition (ECOG score 0-1), and meet specific blood count and organ function criteria. Women of childbearing potential must test negative for pregnancy and agree to use contraception.

Inclusion Criteria

I have advanced GI tumors or MSI-H CRC that hasn't responded well to standard treatments.

I am fully active or can carry out light work.

My advanced cancer hasn't responded to treatment and there's no standard cure.

Exclusion Criteria

I do not have serious heart conditions like heart attacks, uncontrolled high blood pressure, or irregular heartbeats.

For Phase 1b, prior participation in Phase 1a

Known or suspected hypersensitivity to any components of the formulation used for TACH101

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive TACH101 in a 48-hour lead-in period followed by repeated dosing at different regimens in each 28-day cycle

Up to approximately 204 days

Dose Expansion

Participants receive TACH101 at the RP2D identified in Phase 1a, with two cohorts enrolled: gastrointestinal cancers and MSI-H metastatic CRC

Up to approximately 203 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TACH101

Trial Overview

The study tests TACH101's safety, tolerability, dosage levels, how the body processes it, and its effectiveness against tumors. It has two parts: Phase 1a finds the highest dose patients can take without serious side effects; Phase 1b determines a recommended dose for future studies based on responses from participants.

How Is the Trial Designed?

Group I: Phase 1b: Dose Expansion Experimental Treatment 1 Intervention

In Phase 1b, participants will receive TACH101 at the RP2D identified in Phase 1a. Two cohorts of participants will be enrolled: * Participants with gastrointestinal cancers. * Participants with high microsatellite instability (MSI-H) metastatic colorectal cancer (CRC).

Group II: Phase 1a: Dose Escalation Experimental Treatment 1 Intervention

In Phase 1a, participants will receive TACH101 in a 48 hour lead in period followed by repeated dosing at different dosing regimens in each 28 day cycle.

Who Is Running the Clinical Trial?

Tachyon Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study of 41 patients with metastatic colorectal cancer, TAS-102 significantly improved overall survival and progression-free survival, especially when combined with bevacizumab.

Biweekly administration of TAS-102 resulted in significantly less grade ≥3 neutropenia compared to standard administration, suggesting that adjusting the administration method can help manage side effects while maintaining treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly Administration of TAS-102 for Neutropenia Prevention in Patients with Colorectal Cancer. Yoshida, Y., Sakamoto, R., Kajitani, R., et al.[2020]

In a study of 43 patients with metastatic colorectal cancer (mCRC) who were resistant to standard treatments, TAS-102 provided clinically relevant disease control in 30% of patients, particularly those treated for 6 or more cycles, with a median progression-free survival of 7.5 months and overall survival of 11.2 months.

A significant correlation was found between previous treatment success with regorafenib and the efficacy of TAS-102, suggesting that patients who responded well to regorafenib may benefit more from subsequent treatment with TAS-102.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of patients with chemorefractory metastatic colorectal cancer treated with trifluridine/tipiracil (TAS-102): a single Italian institution compassionate use programme. Sforza, V., Martinelli, E., Cardone, C., et al.[2021]

TAS-102 significantly improves overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) in patients with metastatic colorectal cancer (mCRC) compared to placebo or best supportive care, based on a meta-analysis of 2903 patients.

The treatment is effective regardless of KRAS mutation status and does not increase the incidence of serious adverse events, indicating that TAS-102 is both effective and safe for patients whose standard therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of trifluridine/tipiracil (TAS-102) in patients with metastatic colorectal cancer: a systematic review and meta-analysis. Huang, F., Yang, H., Bao, W., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12236304/

Phase 1 study of zavondemstat (TACH101), a first-in-class ...

Zavondemstat was very well tolerated and showed encouraging preliminary clinical benefit in heavily pretreated patients with advanced cancer.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05076552

NCT05076552 | A Study to Assess the Safety, ...

A Phase 1a/1b Open-label Study to Assess the Safety, Pharmacokinetics, and Antitumor Activity of Oral TACH101 in Patients With Advanced or Metastatic Solid ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10569680/

TACH101, a first-in-class pan-inhibitor of KDM4 histone ...

As a pan-KDM4 inhibitor, TACH101 is believed to be potent and efficacious against a broad range of cancers and associated tumor subtypes, as suggested by the ...

4.

withpower.com

withpower.com/trial/phase-1-neoplasm-metastasis-2022-6acd4

Oral TACH101 for Cancer · Info for Participants

TAS-102 significantly improves overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) in patients with metastatic colorectal ...

5.

delta.larvol.com

delta.larvol.com/Products/?ProductId=ebe8630a-104f-46e4-8833-96641e2d428c

zavondemstat (TACH101) / Tachyon

Phase 1 Study of Zavondemstat (TACH101), a First-in-Class KDM4 Inhibitor, in Patients with Advanced Solid Tumors. (PubMed, Oncologist) - "Zavondemstat was ...

6.

journals.lww.com

journals.lww.com/anti-cancerdrugs/fulltext/2023/11000/tach101,_a_first_in_class_pan_inhibitor_of_kdm4.8.aspx

TACH101, a first-in-class pan-inhibitor of KDM4 histone...

TACH101 demonstrated potent antiproliferative activity in cancer cell lines and organoid models derived from various histologies, including colorectal, ...