ARV-766 +/- Abiraterone for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+25 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Novartis Pharmaceuticals

Must be taking: Androgen deprivation therapy

Must not be taking: Steroids, investigational drugs

Disqualifiers: Brain metastases, gastrointestinal disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new oral drug called ARV-766, alone or with abiraterone, in men with advanced prostate cancer that has spread. The drug works by blocking proteins that help cancer cells grow. Abiraterone is a well-established drug used in the treatment of metastatic castration-resistant prostate cancer, often in combination with other therapies.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-cancer therapy at least 2 weeks before starting the study drug, except for medications that maintain castrate status. If you are taking bicalutamide, mitomycin C, or nitrosoureas, you need to stop 6 weeks before, and if you are taking abiraterone, you need to stop 4 weeks before.

What data supports the effectiveness of the drug ARV-766 +/- Abiraterone for prostate cancer?

Research shows that abiraterone, when used with other treatments like enzalutamide, can improve survival in patients with metastatic prostate cancer. This suggests that combining abiraterone with other drugs might be effective in treating prostate cancer. ^{1 2 3 4 5}

Is ARV-766 with or without Abiraterone safe for humans?

There is no specific safety data available for ARV-766, but Abiraterone, which is part of the treatment, has been associated with cardiovascular risks (heart-related issues) in prostate cancer patients. ^{6 7 8 9 10}

How is the drug ARV-766 different from other prostate cancer treatments?

ARV-766 (Luxdegalutamide) is unique because it is being studied in combination with abiraterone for prostate cancer, potentially offering a new approach to treatment. While abiraterone is already used to treat metastatic castration-resistant prostate cancer, ARV-766 may provide additional benefits or work differently, but specific details about its mechanism or advantages are not provided in the available research. ^{11 12 13 14 15}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Men with metastatic prostate cancer who've had progression after at least two systemic therapies, including a second-generation androgen inhibitor. They must have an ECOG performance status of 0 or 1, be on ADT, and can't have had more than two chemo regimens. Exclusions include recent anti-cancer therapy, certain gastrointestinal conditions, symptomatic brain metastases requiring steroids, recent radiation therapy or investigational drugs.

Inclusion Criteria

I am currently on hormone therapy for cancer or have had an orchiectomy.

My prostate cancer has worsened despite two prior treatments, including a modern hormone therapy.

I have taken 1-3 types of specific prostate cancer drugs and no more than 2 chemotherapy treatments for my advanced prostate cancer.

Exclusion Criteria

I have previously been treated with a second generation NHA.

Part A and B: Known symptomatic brain metastases requiring steroids (above physiologic replacement doses). Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease, or previous gastric resection or lap band surgery. Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Receipt of an investigational drug(s) within 4 weeks prior to anticipated first dose. Systemic anti-cancer therapy within 2 weeks of first dose of study drug (except agents to maintain castrate status). For bicalutamide, mitomycin C, or nitrosoureas the exclusion period must be 6 weeks and for abiraterone 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ARV-766 monotherapy or in combination with abiraterone in 28-day cycles

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• ARV-766 (Androgen Receptor Antagonist)

Trial Overview The trial is testing ARV-766 alone (Part A&B) and in combination with abiraterone (Part C&D), taken orally for men with advanced prostate cancer. It's to see how safe they are and how well they work as treatments.

Participant Groups

Group I: ARV-766 + Abiraterone Experimental Treatment 1 Intervention

Oral tablets, once daily in 28 day cycles

Group II: ARV-766 Experimental Treatment 1 Intervention

Oral tablets, once daily in 28 day cycles

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Arvinas Androgen Receptor, Inc.

Lead Sponsor

Trials

4

Recruited

450+

Findings from Research

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In a study involving 1,311 men with metastatic castration-resistant prostate cancer, the addition of abiraterone acetate and prednisone to enzalutamide did not significantly improve overall survival compared to enzalutamide alone, with median survival times of 32.7 months versus 34.2 months, respectively.

However, the combination treatment did result in longer radiographic progression-free survival (24.3 months vs. 21.3 months), indicating some benefit in delaying disease progression, although increased clearance of abiraterone when combined with enzalutamide may have influenced these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase III Study of Enzalutamide Compared With Enzalutamide Plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer (Alliance A031201 Trial). Morris, MJ., Heller, G., Hillman, DW., et al.[2023]

A new non-invasive assay was developed to monitor androgen receptor (AR) expression in circulating tumor cells (CTCs) from 48 metastatic castration-resistant prostate cancer (CRPC) patients, revealing significant variability in AR expression among patients.

The study found that prior treatment with abiraterone or enzalutamide did not change AR expression levels in CTCs, and maintained nuclear AR expression was confirmed in tissue samples from patients who progressed on these treatments, indicating potential resistance mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen receptor expression in circulating tumour cells from castration-resistant prostate cancer patients treated with novel endocrine agents. Crespo, M., van Dalum, G., Ferraldeschi, R., et al.[2022]

In a study of 3808 men with metastatic castration-resistant prostate cancer (mCRPC), African American men receiving first-line abiraterone therapy had a significantly higher median overall survival (23 months) compared to non-Hispanic White men (17 months).

The study found no overall survival difference between first-line abiraterone and enzalutamide for African American men, while non-Hispanic White men had decreased survival with abiraterone compared to enzalutamide, suggesting that race may influence treatment outcomes in mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes Among African American and Non-Hispanic White Men With Metastatic Castration-Resistant Prostate Cancer With First-Line Abiraterone. Marar, M., Long, Q., Mamtani, R., et al.[2022]

In a study involving 1917 men with locally advanced or metastatic prostate cancer, the combination of abiraterone acetate and prednisolone with androgen-deprivation therapy (ADT) significantly improved overall survival compared to ADT alone, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

The combination therapy also resulted in a much lower rate of treatment failure, with a hazard ratio of 0.29, meaning patients were less likely to experience disease progression compared to those receiving only ADT, although it was associated with a higher incidence of grade 3 to 5 adverse events (47% vs. 33%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. James, ND., de Bono, JS., Spears, MR., et al.[2023]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

A meta-analysis of 7 studies involving 8660 patients found that the use of new hormonal agents like abiraterone and enzalutamide significantly increases the risk of cardiovascular toxicity, with relative risks of 1.36 for all-grade and 1.84 for high-grade cardiac toxicity.

Abiraterone specifically raises the risk of both cardiac toxicity and hypertension, while enzalutamide primarily increases the risk of hypertension, highlighting the need for careful monitoring of cardiovascular health in patients undergoing treatment for metastatic prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer. Iacovelli, R., Ciccarese, C., Bria, E., et al.[2021]

In a study of 68 patients with metastatic prostate cancer treated with abiraterone acetate, higher plasma trough concentrations of abiraterone (≥ 20.6 ng/mL) were significantly linked to an increased risk of adverse events (AEs) and treatment withdrawal.

Monitoring abiraterone plasma levels may be beneficial for managing treatment in prostate cancer patients, as high concentrations were identified as independent risk factors for both AEs and the time to discontinue therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of trough abiraterone level on adverse events in patients with prostate cancer treated with abiraterone acetate. Takahashi, Y., Narita, S., Shiota, M., et al.[2023]

In a review of seven randomized controlled trials involving 7103 patients with castration-resistant prostate cancer, abiraterone was found to significantly increase the risk of both any grade (RR = 1.34) and severe grade (RR = 1.71) cardiac disorders.

Enzalutamide was associated with a much higher risk of developing any grade (RR = 2.66) and severe grade (RR = 2.79) hypertension, indicating that while both drugs have cardiovascular risks, they affect different aspects of heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses. Lee, HY., Chen, HL., Teoh, JY., et al.[2022]

A novel RNA in situ hybridization (RISH) assay was developed to specifically detect and quantify androgen receptor splice variant 7 (AR-V7) in prostate cancer biopsies, showing a positive detection rate of 34.1% in metastatic castration-resistant prostate cancer (mCRPC) specimens.

Higher levels of AR-V7 detected using this method were significantly associated with shorter progression-free survival in patients treated with abiraterone or enzalutamide, indicating that AR-V7 may serve as a biomarker for treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Junction-specific and Quantifiable In Situ Detection of AR-V7 and its Clinical Correlates in Metastatic Castration-resistant Prostate Cancer. Zhu, Y., Sharp, A., Anderson, CM., et al.[2023]

In a study of 12 men with metastatic castrate-resistant prostate cancer (mCRPC) who were re-treated with abiraterone acetate (AA), only 46% of those who initially responded to AA showed a similar response upon re-treatment, indicating limited efficacy.

The median duration of response to AA re-treatment was short, with a median biochemical progression-free survival of just 2.3 months, suggesting that re-challenging with AA may not provide significant long-term benefits for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. Leibowitz-Amit, R., Alimohamed, N., Vera-Badillo, FE., et al.[2016]

Abiraterone is an oral medication that inhibits a key enzyme involved in androgen production, making it effective for treating metastatic castration-resistant prostate cancer.

The drug is FDA approved for use in men with this type of cancer, both before and after chemotherapy, and can be administered even to patients on hemodialysis, highlighting its versatility in challenging clinical situations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone experience in a patient with metastatic castration-resistant prostate cancer on hemodialysis. Karakurt Eryılmaz, M., Karaağaç, M.[2020]

In a study involving 2267 patients with metastatic castration-resistant prostate cancer, long-term use of low-dose prednisone (5mg twice daily) with or without abiraterone acetate resulted in a low incidence of corticosteroid-associated adverse events (CA-AEs), with only 25% of patients experiencing any grade CA-AEs.

The most common CA-AEs were hyperglycemia and weight increase, but the overall frequency of these events did not increase with longer exposure to prednisone, indicating that the treatment is safe and tolerable over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer. Fizazi, K., Chi, KN., de Bono, JS., et al.[2022]

In a phase 3 trial involving 1199 patients, the addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly improved overall survival, with a median survival not reached in the abiraterone group compared to 34.7 months in the placebo group.

The study also showed that patients receiving abiraterone had a median radiographic progression-free survival of 33.0 months, compared to 14.8 months in the placebo group, indicating a strong benefit in delaying disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi, K., Tran, N., Fein, L., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. [2023]

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

Randomized Phase III Study of Enzalutamide Compared With Enzalutamide Plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer (Alliance A031201 Trial). [2023]

3. England pubmed.ncbi.nlm.nih.gov

Androgen receptor expression in circulating tumour cells from castration-resistant prostate cancer patients treated with novel endocrine agents. [2022]

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

Outcomes Among African American and Non-Hispanic White Men With Metastatic Castration-Resistant Prostate Cancer With First-Line Abiraterone. [2022]

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

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. [2021]

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

The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Impact of trough abiraterone level on adverse events in patients with prostate cancer treated with abiraterone acetate. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Abiraterone and enzalutamide had different adverse effects on the cardiovascular system: a systematic review with pairwise and network meta-analyses. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Junction-specific and Quantifiable In Situ Detection of AR-V7 and its Clinical Correlates in Metastatic Castration-resistant Prostate Cancer. [2023]

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

Retreatment of men with metastatic castrate-resistant prostate cancer with abiraterone. [2016]

12. England pubmed.ncbi.nlm.nih.gov

Abiraterone experience in a patient with metastatic castration-resistant prostate cancer on hemodialysis. [2020]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Low Incidence of Corticosteroid-associated Adverse Events on Long-term Exposure to Low-dose Prednisone Given with Abiraterone Acetate to Patients with Metastatic Castration-resistant Prostate Cancer. [2022]

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

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. [2022]

15. Germany pubmed.ncbi.nlm.nih.gov

[Early- vs. late-onset treatment using abiraterone acetate plus prednisone in chemo-naïve, asymptomatic or mildly symptomatic patients with metastatic CRPC after androgen deprivation therapy]. [2022]