FASN Inhibitor + Trastuzumab for Breast Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Anti-HER2 therapy

Must not be taking: Tamoxifen

Disqualifiers: Cardiac disease, Brain metastasis, 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: 7

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a new treatment combination for individuals with HER2 positive breast cancer that has metastasized. The treatment combines an FASN inhibitor (TVB-2640), which may inhibit cancer cell growth, with trastuzumab, a targeted therapy that blocks growth signals for cancer cells, and either paclitaxel or endocrine therapy. This combination aims to improve disease control. Eligible participants have HER2 positive breast cancer that has spread and have experienced progression on certain previous treatments. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain therapies like chemotherapy, immunotherapy, biologic therapy, monoclonal antibodies, radiation therapy, CDK 4/6 inhibitors, and mTOR inhibitors must not have been taken within a few weeks before registration.

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

A previous study showed that TVB-2640, a drug that blocks a specific enzyme, has a manageable safety profile. Most side effects were mild and resolved on their own, making it promising for human use. Trastuzumab, a targeted therapy already approved by the FDA for breast cancer, works by attaching to cancer cells and stopping signals that promote growth. It is generally well-tolerated, though some people may experience mild flu-like symptoms.

Paclitaxel, another component of the trial, is a common chemotherapy drug. It has been used for years and is known to cause side effects like hair loss and low blood counts, but these are well-documented and managed.

Researchers are studying the combination of these drugs for safety. Although the trial is in an early phase, existing data is encouraging. Earlier studies have shown TVB-2640's safety, making the combination worth further exploration. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they feature a unique mechanism and combination approach. While many standard treatments like chemotherapy and hormone therapy have a broad focus, the FASN inhibitor TVB-2640 specifically targets the fatty acid synthase (FASN) pathway, which is often overactive in cancer cells, potentially halting their growth. In Cohort A, combining TVB-2640 with paclitaxel and trastuzumab could enhance the treatment's effectiveness by attacking the cancer from multiple angles. In Cohort B, pairing TVB-2640 with trastuzumab and endocrine therapy aims to offer a targeted treatment option with less toxicity. This multi-faceted approach is what makes these treatments stand out from current options.

What evidence suggests that this trial's treatments could be effective for metastatic HER2 positive breast cancer?

Research has shown that combining the drug TVB-2640 with trastuzumab and paclitaxel, as in Cohort A of this trial, may help treat HER2 positive metastatic breast cancer. TVB-2640 blocks an enzyme called fatty acid synthase, which is involved in cell growth, potentially enhancing the effectiveness of other treatments. Studies have found that using TVB-2640 with paclitaxel can help maintain disease stability for longer and may even shrink tumors in some patients. Trastuzumab is a well-known treatment that targets HER2 receptors on cancer cells to inhibit their growth. Together, these treatments might more effectively slow down the disease. ^{1 3 6 7 8}

Who Is on the Research Team?

Tufia C. Haddad, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with HER2 positive metastatic breast cancer. Participants must have good liver and kidney function, a stable heart condition, no severe allergies to the drugs being tested, and not be pregnant or breastfeeding. They should have received fewer than four chemotherapy treatments in the metastatic setting and agree to use contraception.

Inclusion Criteria

You have a tumor that can be measured using specific criteria.

Your aspartate transaminase (AST) level is not more than 3 times the upper limit of normal (or not more than 5 times the upper limit of normal if you have liver involvement).

Cohort A or B specific criteria

Exclusion Criteria

I am immunocompromised or HIV positive and on antiretroviral therapy.

I am not on any experimental drugs for my cancer.

Your heart takes too long to recover between beats.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive FASN inhibitor TVB-2640, paclitaxel, and trastuzumab or endocrine therapy in 28-day cycles

Up to 3 years

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Exemestane
• FASN Inhibitor TVB-2640
• Fulvestrant
• Letrozole
• Paclitaxel
• Trastuzumab

Trial Overview The study tests if TVB-2640 (a FASN inhibitor), combined with trastuzumab and either paclitaxel (chemotherapy) or endocrine therapy, can effectively treat HER2 positive metastatic breast cancer by blocking enzymes needed for cell growth and targeting specific receptors on cancer cells.

How Is the Trial Designed?

Group I: Cohort B (TVB-2640, trastuzumab, endocrine therapy) Experimental Treatment 11 Interventions

Patients receive FASN inhibitor TVB-2640 PO QD on days 1-28 and trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and optionally every 21 days after 3 cycles and paclitaxel is discontinued. Patients also continue endocrine therapy of either anastrozole PO QD, exemestane PO QD, fulvestrant IM on days 1 and 14 of cycle 1 and day 1 of subsequent cycles, or letrozole PO QD. Cycles repeat every 28 days in the absence of disease progression or unexpected toxicity. Patients also undergo ECHO and CT or MRI at screening and on study and undergo collection of blood samples and biopsy on study.

Group II: Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab) Experimental Treatment 8 Interventions

Patients receive FASN inhibitor TVB-2640 PO QD on days 1-28, paclitaxel IV over 1-96 hours on days 1, 8, and 15, and trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and optionally every 21 days after 3 cycles and paclitaxel is discontinued. Cycles repeat every 28 days in the absence of disease progression or unexpected toxicity. Patients also undergo ECHO and CT or MRI at screening and on study and undergo collection of blood samples and biopsy on study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Trastuzumab (Herceptin) has demonstrated significant antitumor activity in patients with HER-2-positive metastatic breast cancer, improving response and survival rates when combined with first-line chemotherapy.

Recent clinical trials have focused on new chemotherapy approaches for node-positive breast cancer, laying the groundwork for ongoing studies that incorporate trastuzumab into treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing and planned adjuvant trials with trastuzumab. Perez, EA., Hortobagyi, GN.[2015]

In the DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) demonstrated superior progression-free survival and overall survival compared to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer, while maintaining quality of life (QoL) throughout treatment.

Patients receiving T-DXd experienced a median time to first hospitalization that was three times longer than those on T-DM1, indicating better overall health management and fewer hospital visits during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study. Curigliano, G., Dunton, K., Rosenlund, M., et al.[2023]

Fam-trastuzumab deruxtecan-nxki is an effective treatment for advanced HER2-positive breast cancer, showing a response rate of 60.9% in major clinical trials, making it a viable option for patients who have not responded to standard therapies.

While the drug is effective, it comes with potential side effects, including serious risks like interstitial lung disease and left ventricular dysfunction, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Fam-Trastuzumab Deruxtecan-nxki in HER2-Positive Breast Cancer. Nguyen, X., Hooper, M., Borlagdan, JP., et al.[2021]

In the phase 2 DESTINY-Breast01 trial, trastuzumab deruxtecan (T-DXd) showed a remarkable objective response rate of 60.9% and a median progression-free survival of 16.4 months in HER2+ metastatic breast cancer patients, supporting its use after multiple prior treatments.

While T-DXd is effective, it has a notable side effect of pneumonitis occurring in 13.6% of patients, leading to warnings for interstitial lung disease and embryo-fetal toxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab deruxtecan for HER2+ advanced breast cancer. Lee, J., Park, YH.[2022]

Fam-trastuzumab deruxtecan-nxki (ENHERTU) received accelerated FDA approval for treating HER2-positive breast cancer in patients who have already undergone two or more anti-HER2 therapies, based on a study involving 184 patients that showed a confirmed overall response rate of 60.3%.

While ENHERTU is effective, it carries significant risks, including severe interstitial lung disease and neutropenia, highlighting the importance of monitoring for serious side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Fam-Trastuzumab Deruxtecan-Nxki for the Treatment of Unresectable or Metastatic HER2-Positive Breast Cancer. Narayan, P., Osgood, CL., Singh, H., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11164988/

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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03179904

TVB-2640 and Trastuzumab With Paclitaxel or Endocrine ... This phase II trial studies how well FASN inhibitor TVB-2640, paclitaxel, and trastuzumab work in treating patients with HER2 positive breast cancer that has ...

3. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00077-8/fulltext

First-in-human study of the safety, pharmacokinetics, and ... The disease control rate (DCR) with TVB-2640 monotherapy was 42%; no patient treated with monotherapy had a complete or partial response (CR or ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842825002987

Therapeutic potential of the fatty acid synthase (FASN) ... FASN blockade shows preclinical efficacy across multiple cancer models. FASN inhibition enhances immune response and may overcome resistance.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.2512

Preliminary activity in the first in human study of the first-in- ... Conclusions: TVB-2640 demonstrated prolonged SD when given in monotherapy and cPR when combined with weekly paclitaxel. Responses were seen ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33870151/

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 adverse events ...

7. 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 ...

8. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.tps2615

First-in-human investigation of the oral first-in-class fatty ... TVB-2640 is a potent, reversible and selective fatty acid synthase (FASN) inhibitor currently in its first Phase 1 study (3V2640-CLIN-002) in patients with ...