TVB-2640 and Trastuzumab With Paclitaxel or Endocrine Therapy for Treatment of HER2 Positive Metastatic Breast Cancer

NCT03179904 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 4 other identifiers: MC1633W81XWH-16-1-0269W81XWH-16-1-026816-010066
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 3

Brief Summary

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 spread to other places in the body (metastatic). FASN inhibitor TVB-2640 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Trastuzumab is a form of targeted therapy because it attaches itself to specific molecules (receptors) on the surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2 receptors, the signals that tell the cells to grow are blocked and the cancer cell may be marked for destruction by the body's immune system. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Estrogen can cause the growth of breast cancer cells. Drugs used in endocrine therapy either lower the amount of estrogen made by the body or blocks the use of estrogen by the tumor cells. This may help stop the growth of tumor cells that need estrogen to grow. Giving FASN inhibitor TVB-2640 and trastuzumab in combination with paclitaxel or endocrine therapy may help control the disease in patients with HER2 positive breast cancer.

Conditions

Advanced Breast Carcinoma; HER2-Positive Breast Carcinoma; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Will be defined as the number of patients whose disease meets the Response Evaluation Criteria in Solid Tumors criteria for a partial or complete response on two consecutive evaluations at least 8 weeks apart divided by the total number of patients in that cohort who started protocol treatment.

  14 months

Secondary Outcomes (3)

• Duration of Response

  14 months

• Clinical Benefit Rate

  41 months

• Progression Free Survival

  41 months

Other Outcomes (1)

• Changes in Biomarker Expression

  Baseline up to 28 days

Study Arms (2)

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab)

EXPERIMENTAL

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.

Drug: Denifanstat; Procedure: Echocardiography; Drug: Paclitaxel; Biological: Trastuzumab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Biopsy

Cohort B (TVB-2640, trastuzumab, endocrine therapy)

EXPERIMENTAL

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.

Drug: Anastrozole; Drug: Denifanstat; Drug: Exemestane; Drug: Fulvestrant; Procedure: Echocardiography; Drug: Letrozole; Biological: Trastuzumab; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Biopsy

Interventions

Anastrozole DRUG

Given PO

Also known as: Anastrazole, Arimidex, ICI D1033, ICI-D1033, ZD-1033

Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Denifanstat DRUG

Given PO

Also known as: ASC 40, ASC-40, ASC40, FASN Inhibitor TVB-2640, TVB 2640, TVB-2640, TVB2640

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab); Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Exemestane DRUG

Given PO

Also known as: Aromasin, FCE-24304

Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Fulvestrant DRUG

Given IM

Also known as: Faslodex, Faslodex(ICI 182,780), ICI 182,780, ICI 182780, ZD9238

Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab); Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab)

Trastuzumab BIOLOGICAL

Given IV

Also known as: 180288-69-1, ABP 980, ALT02, Biceltis, CANMab, CT-P06, CT-P6, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Herclon, Hertraz, Herzuma, Immunoglobulin G 1 (Human-Mouse Monoclonal RhuMab HER2gamma1-Chain Antihuman p185(Sup c-erbB2) Receptor), Disulfide with Human-Mouse Monoclonal RhuMab HER2 Light Chain, Dimer, Kanjinti, Ogivri, Ontruzant, PF-05280014, QL 1701, QL-1701, QL1701, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, Trastuzumab Biosimilar CT-P6, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar QL1701, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-qyyp, Trazimera

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab); Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, computerized axial tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT SCAN, tomography

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab); Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: MRI, Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI Scan, MRIs, NMRI, nuclear magnetic resonance imaging, sMRI, Structural MRI

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab); Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab); Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Cohort A (FASN inhibitor TVB-2640, paclitaxel, trastuzumab); Cohort B (TVB-2640, trastuzumab, endocrine therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>=18 years
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria that is:
• A non-nodal lesion is considered measurable if its longest diameter can be accurately measured as \>= 1.0 cm with computed tomography (CT) scan, CT component of a positron emission tomography (PET)/CT, or magnetic resonance imaging (MRI) and/or
• A malignant lymph node is considered measurable if its short axis is \> 1.5 cm when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm)
• Note: tumor lesions in a previously irradiated area are not considered measurable disease; disease that is measurable by physical examination only is not eligible
• Received =\< six (6) prior chemotherapy regimens in the metastatic setting
• Cohort A one of the following must be true:
• Distant disease progression during administration of combination therapy with taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) for metastatic disease
• Note: patients who began treatment with this combination and discontinued taxane-based chemotherapy due to intolerability before distant disease progression are eligible
• Distant disease progression during administration or within 180 days of discontinuing combination therapy with taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) in the adjuvant disease
• Note: patients who began treatment with this combination and discontinued taxane-based chemotherapy due to intolerability before distant disease progression are eligible
• For patient who received taxane based chemotherapy and anti-HER2 therapy (trastuzumab or pertuzumab) in the neo-adjuvant setting and underwent surgical resection of primary breast disease: distant disease progression during or within 180 days of discontinuing anti-HER2 therapy (trastuzumab or pertuzumab) in the adjuvant setting
• Cohort B (one of the following must be true):
• Distant disease progression during administration of combination therapy with endocrine therapy and anti-HER2 therapy (trastuzumab or pertuzumab) for metastatic disease; permissible endocrine therapies include an aromatase inhibitor or fulvestrant
• NOTE: Tamoxifen is not permissible

You may not qualify if:

• Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity
• Patients with a history of LVEF decline to below 50% during or after prior trastuzumab or other HER2 directed therapy =\< 6 months prior to pre-registration
• Patients with any class of New York Heart Association (NYHA) congestive heart failure (CHF) or heart failure with preserved ejection fraction (HFPEF)
• Patients with a history of known coronary artery disease or a myocardial infarction within 12 months prior to pre-registration
• Patients with persistently uncontrolled hypertension (systolic blood pressure \[BP\] \> 160 mm Hg or diastolic BP \> 100 mm Hg) despite optimal medical therapy
• Patients with known unstable angina pectoris
• Patients with a known history of serious cardiac arrhythmias requiring treatment (exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia)
• Patients with a prolonged corrected QT interval (QTc) interval (\>= 450 ms)
• Leptomeningeal disease or uncontrolled brain metastasis
• NOTE: Metastases treated by surgery and/or radiotherapy such that patient is neurologically stable and off steroids \>= 4 weeks prior to preregistration are eligible
• Failure to recover from acute, reversible effects of prior therapy regardless of interval since last treatment
• EXCEPTION: Grade 1 peripheral (sensory) neuropathy that has been stable for at least 3 months since completion of prior treatment
• Tumors involving spinal cord or heart
• Visceral crisis or lymphangitic spread
• NOTE: Visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of disease

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

Anastrozole; TVB-2640; exemestane; Fulvestrant; Letrozole; Paclitaxel; Taxes; Trastuzumab; CT-P6; PF-05280014; Disulfides; Ogivri; Ontruzant; trastuzumab biosimilar HLX02; Magnetic Resonance Spectroscopy; X-Rays; Specimen Handling; Biopsy

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Tufia Haddad
• Organization: Mayo Clinic

haddad.tufia@mayo.edu

507-293-0526

Study Officials

• Tufia C. Haddad, M.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 7, 2017
• Study Start: August 3, 2017
• Primary Completion: July 30, 2024
• Study Completion (Estimated): June 13, 2026
• Last Updated: May 5, 2026
• Results First Posted: February 24, 2026

Record last verified: 2026-04

Locations

US (3)