Study of TVB-2640 in Men With Metastatic Castration-Resistant Prostate Cancer

NCT05743621 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 22-08025117
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine what effects (good and bad) Enzalutamide and TVB-2640 have in the treatment of prostate cancer whose prostate cancer has spread to other parts of their body and that has not gotten better with previous treatment. This study is a Phase I clinical trial. Phase I clinical trials test the side effects of an investigational drug or an investigational combination with another drug. "Investigational" means that the drug is still being studied and research doctors are trying to find out more about it. Although Enzalutamide is already being used to treat men with prostate cancer, combining Enzalutamide with TVB-2640 together in patients with prostate cancer is considered experimental. This research study is being done because additional effective treatments are needed for prostate cancer that has spread and is growing despite hormone suppression. By doing this study, the investigators hope to learn if combining Enzalutamide with TVB-2640 can be done safely. Participation in this research will last about 12 to 24 months after enrollment.

Conditions

Prostatic Neoplasms, Castration-Resistant

Keywords

Metastatic Castration-Resistant Prostate Cancer; FASN Inhibitor

Outcome Measures

Primary Outcomes (1)

• Optimal dose of TVB-2640 in combination with Enzalutamide, as determined by the maximum tolerated dose (MTD)

  The maximum tolerated dose (MTD) is defined as the highest dose level at which ≤1 patient experiences a dose-limiting toxicity, as defined in the protocol (DLT). Once all the patients are accrued, the MTD will be determined by performing isotonic regression on the pooled data.

  Day 28

Secondary Outcomes (19)

• Number of adverse events (evaluated using the NCI CTCAE v5.0) of different doses of TVB-2640 in combination with Enzalutamide

  12 months

• Mean TVB-2640 total exposure (as measured by the area under the drug serum concentration vs. the time from administration curve [AUC])

  Day 28; Days 36-37; Days 43-44; Days 50-51

• Mean Enzalutamide total exposure (as measured by the area under the drug serum concentration vs. the time from administration curve [AUC])

  Day 28; Days 36-37; Days 43-44; Days 50-51

• Mean maximum serum concentration (Cmax) of TVB-2640

  Day 28; Days 36-37; Days 43-44; Days 50-51

• Mean maximum serum concentration (Cmax) of Enzalutamide

  Day 28; Days 36-37; Days 43-44; Days 50-51

Study Arms (1)

TVB-2640 in combination with Enzalutamide

EXPERIMENTAL

Drug: TVB-2640; Drug: Enzalutamide

Interventions

TVB-2640 DRUG

TVB- 2640 at 100 mg, 150mg, 200 mg, 250 mg, or 300mg daily, orally; dose determined by BOIN dose escalation per the protocol

TVB-2640 in combination with Enzalutamide

Enzalutamide DRUG

160 mg daily PO

Also known as: Xtandi

TVB-2640 in combination with Enzalutamide

Eligibility Criteria

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

You may qualify if:

• Age \>18 years
• Documented histological or cytological diagnosis of PC
• Evidence of metastatic PC on imaging (bone scan and/or CT/MRI scan)
• Diagnosis of progressive metastatic, castration resistant prostate cancer
• Potential participant must be planning to receive Enzalutamide as their first line of therapy for castration resistant prostate cancer or have previously received up to one line of Abiraterone or an androgen receptor antagonist
• Willing to undergo a tumor biopsy prior to beginning therapy, if recent tissue samples are not available
• Willing to undergo a tumor biopsy of at least one metastatic site or primary prostate after \~4-6 weeks of therapy with both agents
• Participants without prior orchiectomy must be currently taking and willing to continue luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) therapy until permanent discontinuation of study treatment
• ECOG performance status of 0-1
• Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless specified below AE(s) are clinically nonsignificant and/or stable on supportive therapy
• Adequate organ and marrow function, based upon laboratory criteria within 14 days before first dose of study treatment
• Sexually active, fertile participants and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom with spermicide during the course of the study and for 4 months after the last dose of study treatment
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document

You may not qualify if:

• Receipt of any type of biologic, or other systemic anticancer therapy (including investigational) except agents within 4 weeks before first dose of study treatment. Anti-resorptive bone agents are also allowed.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Prior exposure to taxane chemotherapy
• History of pneumonitis
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Participants must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible participants must be neurologically asymptomatic and without corticosteroid treatment for neurological indications at the time of first dose of study treatment.
• Participants with clinically significant dry eye or corneal abnormalities
• Currently taking certain anticoagulation medications, such as coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel)
• Participant has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 X the laboratory ULN within 30 days before the first dose of study treatment.
• Participants should not receive strong CYP2C8 or strong P-gp inhibitors; strong CYP3A4 or CYP2C8 inducers; and strong CYP3A4, CYP2C9 and CYP2C19 substrates while participating in the trial, unless utilized with caution to treat a drug-related AE when no alternative is available and discussed with the Medical Monitor.
• Participant has uncontrolled, significant intercurrent or recent Cardiovascular disorders including, but not limited to, the following conditions:
• i. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \>140 mm Hg systolic or \>90 mm Hg diastolic despite optimal antihypertensive treatment.
• iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g. deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 470 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
• Inability to swallow tablets.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Sagimet Biosciences Inc.: collaborator

Study Sites (1)

Weill Cornell Medicine/NewYork-Presbyterian Hospital

New York, New York, 10021, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

TVB-2640; enzalutamide

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• David Nanus, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

GUONC Research Team

CONTACT

646-962-2072; guonc@med.cornell.edu

Escarleth Fernandez

CONTACT

646-962-9406; esf4001@med.cornell.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 24, 2023
• Study Start: November 20, 2023
• Primary Completion (Estimated): January 25, 2027
• Study Completion (Estimated): January 25, 2029
• Last Updated: November 21, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)