ARV-110 + Abiraterone for Prostate Cancer

Recruiting at 19 trial locations

Overseen By Arvinas Androgen Receptor, Inc.

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Arvinas Androgen Receptor, Inc.

Must be taking: Abiraterone, Corticosteroids, GnRH analogues

Must not be taking: Chemotherapy, Immunotherapy, Hormonal therapy

Disqualifiers: Untreated brain metastases, Active malignancy, Cardiac issues, others

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

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1b study to assess the combination of ARV-110 and abiraterone in patients with metastatic prostate cancer with rising PSA values on abiraterone.

Will I have to stop taking my current medications?

Participants must continue taking abiraterone and a corticosteroid as part of the trial. However, if you are taking certain other medications, like those affecting specific enzymes or proteins, you may need to stop or adjust them. It's best to discuss your current medications with the trial team to see if any changes are needed.

What data supports the effectiveness of the drug Abiraterone in treating prostate cancer?

Research shows that Abiraterone, when combined with prednisone, significantly extends the life of patients with metastatic castration-resistant prostate cancer compared to a placebo. This combination also delays the progression of the disease, making it an effective treatment option. ^{1 2 3 4 5}

Is the combination of ARV-110 and Abiraterone safe for humans?

Abiraterone, used in combination with prednisone, has been approved for treating prostate cancer and has been shown to be generally safe in clinical trials, although it may have side effects. However, specific safety data for the combination of ARV-110 and Abiraterone is not provided in the available research. ^{1 2 3 4 5}

What makes the drug ARV-110 + Abiraterone unique for prostate cancer?

ARV-110 combined with Abiraterone is unique because it potentially offers a novel mechanism of action by targeting and degrading specific proteins involved in prostate cancer progression, which may provide an alternative for patients who have not responded to other treatments. ^{1 2 3 4 6}

Eligibility Criteria

Men with metastatic castration-resistant prostate cancer who have rising PSA levels despite ongoing abiraterone treatment. They should be in good physical condition (ECOG status of 0 or 1) and on stable hormone therapy. Excluded are those with recent major surgery, uncontrolled infections, severe heart conditions, electrolyte imbalances, brain metastases requiring steroids, or other active cancers.

Inclusion Criteria

My PSA levels have increased 16 weeks after starting abiraterone.

My PSA levels have increased 16 weeks after starting abiraterone.

I am currently on stable doses of abiraterone and a steroid for my metastatic prostate cancer.

Exclusion Criteria

Patients with QTcF ≥470 msec.

I do not have any active, uncontrolled infections including HIV/AIDS or hepatitis.

Patients with electrolyte imbalances of hypokalemia, hypomagnesemia, and/or hypocalcemia

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ARV-110 in combination with abiraterone and a corticosteroid administered daily in 28-day cycles

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 weeks

2 visits (in-person)

Treatment Details

Interventions

• Abiraterone
• ARV-110

Trial Overview The trial is testing the combination of a new drug called ARV-110 with an existing medication named Abiraterone to see if it can help men whose prostate cancer continues to progress as indicated by rising PSA levels even after being treated with Abiraterone alone.

Participant Groups

Group I: Oral tablet(s) in combination with abiraterone and a corticosteroid. Experimental Treatment 1 Intervention

ARV-110 oral tablets in combination with abiraterone and a corticosteroid administered daily in 28 day cycles.

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

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer (mCRPC)
• Metastatic high-risk castration-sensitive prostate cancer (mCSPC)

Who Is Running the Clinical Trial?

Arvinas Androgen Receptor, Inc.

Lead Sponsor

Trials

4

Recruited

450+

Findings from Research

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

In a Swedish observational study of 119 patients with metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate treatment resulted in similar overall survival rates compared to those seen in the pivotal clinical trial, despite a shorter median treatment duration of 5.6 months versus 7.3 months in the trial.

The findings suggest that while Swedish patients may have characteristics that could limit their treatment benefits, they still achieve comparable survival outcomes, indicating a potentially more cost-effective use of abiraterone in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. Svensson, J., Andersson, E., Persson, U., et al.[2017]

Abiraterone acetate, in combination with prednisone, received full FDA approval for treating metastatic castration-resistant prostate cancer (mCRPC) based on the COU-AA-302 trial, which involved 1,088 patients and showed a significant improvement in radiographic progression-free survival (rPFS) compared to placebo (8.3 months vs. not reached).

The trial also indicated a favorable trend in overall survival (OS) for patients receiving abiraterone acetate, although it did not reach statistical significance, confirming the drug's efficacy and safety profile consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. Kluetz, PG., Ning, YM., Maher, VE., et al.[2018]

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

Abiraterone acetate (Zytiga®) is an effective antiandrogen for prostate cancer but has poor oral bioavailability (<10%) and requires patients to fast around its administration due to a significant food effect (5-10-fold increase in absorption).

The review highlights the need for improved oral formulation strategies to enhance solubility and bioavailability of abiraterone acetate, aiming to reduce the required dose and eliminate the food effect, which could lead to better patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. Schultz, HB., Meola, TR., Thomas, N., et al.[2020]

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]

References

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

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

2. Sweden pubmed.ncbi.nlm.nih.gov

Value of treatment in clinical trials versus the real world: the case of abiraterone acetate (Zytiga) for postchemotherapy metastatic castration-resistant prostate cancer patients in Sweden. [2017]

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

Abiraterone acetate in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer: U.S. Food and Drug Administration drug approval summary. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020]

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

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