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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug 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 trials, it increased survival by nearly 5 months and reduced levels of prostate-specific antigen, a marker of prostate cancer. ^{1 2 3 4 5}

Is the combination of TVB-2640 and Enzalutamide safe for humans?

Enzalutamide (also known as Xtandi) is generally well-tolerated in humans, with a phase III trial showing it improved survival in prostate cancer patients. However, it has been associated with a rare skin reaction called acute generalized exanthematous pustulosis (a type of rash). There is no specific safety data available for TVB-2640 in this context. ^{1 2 3 5 6}

What makes the drug combination of TVB-2640 and Enzalutamide unique for prostate cancer?

The combination of TVB-2640 and Enzalutamide is unique because it pairs a novel androgen receptor inhibitor (Enzalutamide) with TVB-2640, which may offer a new approach to treating prostate cancer by targeting different pathways involved in cancer progression. This combination could potentially enhance treatment effectiveness compared to using Enzalutamide alone. ^{1 2 3 7 8}

Research Team

David Nanus, M.D.

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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.

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

I am willing to have a biopsy if my recent tissue samples are not available.

Exclusion Criteria

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.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. [2021]

2. Poland pubmed.ncbi.nlm.nih.gov

Enzalutamide induced acute generalized exanthematous pustulosis. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020]

4. Switzerland 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel antiandrogen for patients with castrate-resistant prostate cancer. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. New Zealand pubmed.ncbi.nlm.nih.gov

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

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