TVB-2640 + Enzalutamide for Prostate Cancer

Overseen By GUONC Research Team

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Weill Medical College of Cornell University

Must be taking: LHRH analogues

Must not be taking: Anticoagulants, CYP inhibitors

Disqualifiers: Brain metastases, Seizure history, others

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial explores the effects of combining two drugs, Enzalutamide and TVB-2640 (an experimental treatment), to treat prostate cancer that has spread and is not responding to current treatments. The goal is to determine if this combination is safe and effective. Men with prostate cancer that continues to grow despite hormone treatments and who have not undergone chemotherapy may be suitable candidates. Participants must be open to having tumor biopsies (tissue samples taken) during the study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain anticoagulation medications or strong inhibitors and inducers of specific enzymes. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research has shown that Enzalutamide, a drug already used for prostate cancer, is generally well-tolerated by patients. One study found that it helped men with advanced prostate cancer live longer. However, it can still cause side effects like tiredness or high blood pressure.

Regarding TVB-2640, research remains in the early stages. The goal is to determine the safest dose when used with Enzalutamide. Researchers closely monitor for any side effects. Although limited data exists on its safety in humans, using these two drugs together is considered experimental.

Overall, the safety of combining Enzalutamide with TVB-2640 is still under study. Patients in the trial receive close monitoring to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of TVB-2640 and Enzalutamide for treating prostate cancer because it brings a fresh approach to tackling the disease. Most treatments for prostate cancer, like hormone therapies, focus on blocking androgens that fuel cancer growth. However, TVB-2640 works differently by targeting fatty acid metabolism, which cancer cells use for energy and growth. This dual approach not only aims to cut off the cancer's hormonal fuel but also its energy supply, potentially making it more effective than current treatment options alone.

What evidence suggests that combining Enzalutamide with TVB-2640 could be effective for prostate cancer?

Research has shown that Enzalutamide helps patients with advanced prostate cancer live longer. This drug is already used for prostate cancer that has spread and doesn't respond to hormone therapy. In this trial, participants will receive a combination of Enzalutamide and TVB-2640, a new drug that inhibits a key enzyme involved in fat production, which is often overactive in prostate cancer. The researchers aim to determine if adding TVB-2640 to Enzalutamide enhances treatment effectiveness. Early studies suggest this combination could be more effective than using Enzalutamide alone. While more research is needed, this combination appears promising for those whose cancer hasn't responded to other treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

David Nanus, M.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

Men over 18 with metastatic, castration-resistant prostate cancer that hasn't improved with prior treatment can join. They must be willing to undergo biopsies and have not had cytotoxic chemotherapy for hormone-sensitive prostate cancer. Participants should plan to take Enzalutamide as their first therapy or have had one line of similar treatments.

Inclusion Criteria

I agree to have a biopsy of my cancer after 4 weeks of treatment.

I have not had chemotherapy that kills cells.

Sexually active, fertile participants and their partners must agree to use medically accepted methods of contraception during the study and for 4 months after the last dose of study treatment

Exclusion Criteria

I haven't had radiation for bone metastasis in 2 weeks, other radiation in 4 weeks, or radionuclide treatment in 6 weeks.

I have received chemotherapy for hormone-sensitive prostate cancer.

I haven't had any cancer treatment except for bone agents in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enzalutamide Run-in

Participants receive Enzalutamide monotherapy at the approved dose of 160 mg once daily for 28 days to reach steady state

4 weeks

Weekly visits for blood draws

Dose Escalation

Participants receive TVB-2640 in combination with Enzalutamide, with dose escalation to determine the maximum tolerated dose

8-20 weeks

Frequent visits for blood draws and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• TVB-2640

Trial Overview The trial is testing the combination of TVB-2640 and Enzalutamide in treating advanced prostate cancer. It's a Phase I study, which means it's mainly looking at the safety and side effects of this new drug combo.

How Is the Trial Designed?

Group I: TVB-2640 in combination with Enzalutamide Experimental Treatment 2 Interventions

Enzalutamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in European Union as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Canada as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Approved in Japan as Xtandi for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Non-metastatic castration-resistant prostate cancer (nmCRPC)

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Sagimet Biosciences Inc.

Industry Sponsor

Trials

10

Recruited

3,900+

Published Research Related to This Trial

In a phase III trial involving patients with metastatic, castration-resistant prostate cancer (mCRPC) who had progressed after docetaxel treatment, enzalutamide significantly improved overall survival, with a median survival of 18.4 months compared to 13.6 months for placebo, indicating a 37% reduction in mortality risk.

Enzalutamide was generally well tolerated, with most side effects being mild to moderate, although there is a small, dose-dependent risk of seizures; it also improved quality of life and pain management for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in metastatic, castration-resistant prostate cancer. Sanford, M.[2021]

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

Enzalutamide, a treatment for metastatic castration-resistant prostate cancer, was linked to a case of acute generalized exanthematous pustulosis (AGEP) in a 62-year-old male patient, indicating a potential skin-related side effect of this medication.

The patient's skin reaction occurred shortly after starting enzalutamide and resolved within four weeks, suggesting that the long half-life of enzalutamide (5.8 days) may contribute to the prolonged duration of symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. Alberto, C., Konstantinou, MP., Martinage, C., et al.[2020]

In a long-term study of 67 patients with hormone-naïve prostate cancer, enzalutamide monotherapy resulted in a 100% prostate-specific antigen (PSA) response rate at 97 weeks for those who remained on treatment, indicating its strong efficacy.

The treatment was well-tolerated with minimal negative effects on total-body bone mineral density, although common side effects included gynecomastia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Tombal, B., Borre, M., Rathenborg, P., et al.[2021]

Enzalutamide (XTANDI) is an FDA-approved treatment for castration-resistant prostate cancer (CRPC) that effectively targets androgen receptor signaling, which is crucial for cancer progression.

In a Phase III clinical trial involving men with CRPC after chemotherapy, enzalutamide was well tolerated and significantly improved overall survival by 4.8 months, as indicated by reduced serum prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. Dhingra, R., Sharma, T., Singh, S., et al.[2021]

In a phase III study involving men with progressive castration-resistant prostate cancer, enzalutamide significantly improved overall survival compared to placebo, with a median survival of 18.4 months versus 13.6 months.

Enzalutamide also showed benefits across all secondary endpoints, including a higher rate of prostate-specific antigen (PSA) decline and improved quality of life, although it was associated with common side effects like fatigue and diarrhea, and a rare incidence of seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer. Hoffman-Censits, J., Kelly, WK.[2021]

Enzalutamide treatment leads to different gene expression profiles (transcriptomes) in prostate cancer cells compared to small-cell carcinoma cells, suggesting that the drug may affect these cancer types differently.

Understanding these distinct transcriptomes can help in tailoring more effective treatment strategies for patients with prostate cancer and small-cell carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Cell Transcriptomics Reveal Treatment Effects in Prostate Cancer. [2021]

In the PREVAIL trial, enzalutamide significantly improved both radiographic progression-free survival and overall survival in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (CRPC), demonstrating its efficacy as a treatment option.

Enzalutamide was well tolerated and delayed the need for chemotherapy and decline in health-related quality of life, making it a convenient choice for patients who are asymptomatic or mildly symptomatic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a review of its use in chemotherapy-naïve metastatic castration-resistant prostate cancer. Keating, GM.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05743621

NCT05743621 | Study of TVB-2640 in Men With Metastatic ... 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.TPS248

A phase I, open-label, dose-finding study of fatty acid ... TVB-2640 is a first-in-class FASN inhibitor, a key enzyme in de novo lipogenesis that is overexpressed and androgen-regulated in CRPC.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05743621?term=AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Prostatic%20Neoplasms,%20Castration-Resistant%22))&rank=4

Study of TVB-2640 in Men With Metastatic Castration ... 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 ...

4. jcto.weill.cornell.edu jcto.weill.cornell.edu/open_clinical_trials/a-phase-i-open-label-dose-finding-study-of-tvb-2640-administered-in-combination-with-enzalutamide-xtandi-in-men-with-metastatic-castration-resistant-prostate-cancer-mcrpc

A Phase I, Open-Label, Dose-Finding Study of TVB-2640 ... This is a research study to evaluate the safety and tolerability of an experimental drug called TVB-2640 in combination with Enzalutamide for men with ...

5. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-1-2023-4817b

TVB-2640 + Enzalutamide for Prostate Cancer Research shows that Enzalutamide, a drug used for prostate cancer, significantly improves survival in patients with advanced stages of the disease. In clinical ...