TVB-2640 for Non-Small Cell Lung Cancer

Not currently recruiting at 1 trial location

Overseen By Ebele Mbanugo, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: David E Gerber

Must not be taking: CYP3A4/5 modulators, QT prolongers

Disqualifiers: GI disease, Heart failure, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TVB-2640 for individuals with non-small cell lung cancer (NSCLC) that has a specific gene change known as a KRAS mutation. The goal is to determine if TVB-2640 can benefit patients whose cancer has progressed despite other treatments. It targets those with advanced or metastatic NSCLC who have already undergone chemotherapy and immunotherapy. Participants should have shown progression on their last treatment and possess measurable cancer for doctors to track. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use strong CYP3A4/5 agonists or inhibitors during the study. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.

Is there any evidence suggesting that TVB-2640 is likely to be safe for humans?

Research has shown that TVB-2640 is generally safe and well-tolerated in people. Studies have found its safety profile to be predictable, with mostly known, non-severe, and reversible side effects.

In another study involving patients with a different type of cancer, TVB-2640 was well-tolerated when combined with another drug. This suggests it might also be safe for individuals with non-small cell lung cancer (NSCLC).

Overall, the evidence indicates that TVB-2640 could be a safe option, but further research is needed to confirm this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for non-small cell lung cancer, which often include chemotherapy and targeted therapies like EGFR inhibitors, TVB-2640 offers a fresh approach by targeting cancer metabolism. TVB-2640 is an oral drug that inhibits fatty acid synthase, an enzyme crucial for cancer cell growth and survival. Researchers are excited about this treatment because it could potentially disrupt the energy supply of cancer cells, weakening them and making them more susceptible to other therapies. Its unique mechanism of action opens new possibilities for tackling cancer resistance to existing treatments.

What evidence suggests that TVB-2640 might be an effective treatment for non-small cell lung cancer?

Research has shown that TVB-2640, the investigational treatment in this trial, targets a protein called fatty acid synthase (FASN), which is often overly active in cancers like non-small cell lung cancer (NSCLC). Lab studies have demonstrated that this drug can stop tumor growth. In early human studies, TVB-2640 proved safe and reduced cancer-related activities. It also worked well with other cancer drugs in various cancer types, suggesting potential effectiveness against NSCLC, particularly in patients with KRAS mutations. This raises hope that TVB-2640 could help stop or slow cancer growth. ^{1 3 6 7 8}

Who Is on the Research Team?

David Gerber, MD

Principal Investigator

Professor

Are You a Good Fit for This Trial?

This trial is for adults with advanced stage Non-Small Cell Lung Cancer (NSCLC) that has a specific KRAS mutation and has worsened despite previous treatments including chemotherapy and immune therapy. Participants must have good organ function, no severe heart disease or infections, not be pregnant, and agree to use contraception.

Inclusion Criteria

My cancer has a KRAS mutation confirmed by a certified test.

My cancer has worsened despite my latest treatment.

You are expected to live for more than 3 months.

Exclusion Criteria

I have HIV or hepatitis B/C.

I need to take strong medication that affects liver enzymes during the study.

I don't have another cancer that could affect this treatment's safety or results.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TVB-2640 100mg/m2 orally once a day for 8 weeks

8 weeks

Visits every 4 weeks for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Patients with stable disease or partial/complete remissions will continue therapy

Until disease progression or unacceptable toxicity

What Are the Treatments Tested in This Trial?

Interventions

• TVB-2640

Trial Overview The study tests TVB-2640 in patients with KRAS mutant NSCLC. It's a phase 2 trial where all participants receive the drug over an 8-week period to see how effective it is against their cancer after other treatments have failed.

How Is the Trial Designed?

Group I: TVB-2640 Experimental Treatment 1 Intervention

Patients will be administered TVB-2640 100mg/m2 orally once a day for 8 weeks.

Who Is Running the Clinical Trial?

David E Gerber

Lead Sponsor

Trials

1

Recruited

20+

Gateway for Cancer Research

Collaborator

Trials

47

Recruited

2,500+

Sagimet Biosciences Inc.

Industry Sponsor

Trials

10

Recruited

3,900+

Cancer Prevention Research Institute of Texas

Collaborator

Trials

55

Recruited

98,900+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8040281/

First-in-human study of the safety, pharmacokinetics, and ... TVB-2640 demonstrated potent FASN inhibition and a predictable and manageable safety profile, primarily characterized by non-serious, reversible ...

2. sagimet.com sagimet.com/wp-content/uploads/2015/06/3VB_42x72_MetabCancer2015_Clinical-Trial-Poster_8June2015.pdf

Translational Studies of a First-in-class FASN Inhibitor, TVB ... TVB-2640 is an oral, first-in-class, small-molecule reversible inhibitor of FASN that demonstrates in vitro and in vivo anti- tumor effects with an acceptable ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT166391

Preliminary activity in the first in human study of the ... Preliminary activity in the first in human study of the first-in-class fatty acid synthase (FASN) inhibitor, TVB-2640. · Author Details · Emma Jane Dean · Abstract ...

4. nature.com nature.com/articles/s41523-024-00656-0

Targeting fatty acid synthase in preclinical models of TNBC ... We demonstrate that the fatty acid synthase inhibitor TVB-2640 synergizes with the topoisomerase inhibitor SN-38 in triple-negative breast cancer (TNBC) BM ...

5. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.899987/full

The Deubiquitinase USP13 Maintains Cancer Cell ... More importantly, the small molecule inhibitor of FASN, TVB-2640, significantly inhibits lipogenic phenotype and attenuates self-renewal ability, chemotherapy ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03808558

NCT03808558 | Phase 2 Study of TVB-2640 in KRAS Non- ... This is a prospective one-arm, two-stage phase 2 trial of TVB-2640 in KRAS mutant NSCLC patients. 13 patients will be treated with a minimum of 1 cycle of TVB- ...

7. sagimet.com sagimet.com/programs/

Programs FASN Inhibitor Non-small cell lung cancer/KRAS mutation – Positive preclinical combination results with KRAS inhibitor, encouraging results observed in patients with NSCLC ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10320469/

Phase II Investigation of TVB-2640 (Denifanstat) with ... In this phase II study of relapsed high-grade astrocytoma, TVB-2640 was found to be a well-tolerated oral drug that could be safely combined with bevacizumab.