ARV-110 + Abiraterone for Prostate Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications for men with metastatic prostate cancer. Researchers are examining whether adding ARV-110, an experimental treatment, to the current regimen of abiraterone can help control cancer when PSA levels rise. Ideal participants have prostate cancer that has spread, are already taking abiraterone and a corticosteroid, and have rising PSA levels without new cancer growths on scans. 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?

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.

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

Studies have shown that ARV-110 can help patients with prostate cancer. In earlier research, patients tolerated ARV-110 well, experiencing only mild or moderate side effects. These studies focused on patients with advanced prostate cancer who had already tried other treatments.

Abiraterone, a drug already used to treat prostate cancer, is generally well-tolerated. It works by lowering hormone levels that can help the cancer grow. Common side effects include fatigue and joint pain.

Researchers are still studying the combination of ARV-110 and abiraterone, but early research suggests the combination could be safe for patients. This trial is in an early stage, so researchers are still learning about how these drugs work together and their safety. However, the existing information about each drug separately is promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about ARV-110 in combination with abiraterone for prostate cancer because ARV-110 introduces a novel mechanism of action. Unlike traditional treatments that inhibit androgen receptors, ARV-110 is a PROTAC (Proteolysis Targeting Chimera) that degrades these receptors, potentially overcoming resistance to current therapies. This innovative approach could provide a new pathway to combat prostate cancer, especially in cases where tumors have become resistant to existing treatments.

What evidence suggests that the combination of ARV-110 and abiraterone could be effective for metastatic prostate cancer?

Research shows that ARV-110 targets and breaks down proteins that promote cancer growth, particularly in prostate cancer with certain mutations. Studies have found that ARV-110 is effective in models with these mutations. Abiraterone is already a well-known treatment for prostate cancer. In this trial, participants will receive a combination of ARV-110 and abiraterone, along with a corticosteroid. This combination aims to improve outcomes, especially for patients whose cancer continues to grow with just abiraterone. Early evidence suggests this combination could be promising, offering a new option for those with advanced prostate cancer. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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

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

Patients with QTcF ≥470 msec.

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05177042

Study Details | NCT05177042 | Trial of ARV-110 and ... Phase 1b study to assess the combination of ARV-110 and abiraterone in patients with metastatic prostate cancer with rising PSA values on abiraterone.

2. studypages.com studypages.com/s/trial-of-arv-110-and-abiraterone-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc-325345/?ref=gallery

Trial of ARV-110 and Abiraterone in Patients With ... The main purpose of this study is to learn more about the combination of two drugs, ARV-110 and abiraterone, when used in combination in patients with ...

3. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-2022-622d1

ARV-110 + Abiraterone for Prostate Cancer Phase 1b study to assess the combination of ARV-110 and abiraterone in patients with metastatic prostate cancer with rising PSA values on abiraterone. Show more.

4. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-arv-110-for-mcrpc

FDA Grants Fast Track Designation to ARV-110 for mCRPC Preclinical data have demonstrated that ARV-110 has activity in models with AR mutations or overexpression. In the ongoing, first-in-human ...

5. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/trial-of-arv-110-and-abiraterone-in-patients-with-metastatic-castration-resistant-prostate-cancer/

Trial of ARV-110 and Abiraterone in Patients ... The first part of the study is to determine the dose of both ARV-110 and Abiraterone when taken together. The starting dose of ARV-110 will be 420 mg daily, ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.6_suppl.017

Phase 1/2 study of ARV-110, an androgen receptor (AR) ... Previous phase 1 data indicated clinical activity for ARV-110 in heavily pretreated pts with mCRPC and suggested enhanced activity in pts with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10854644/

Insight into Recent Advances in Degrading Androgen ... ARV-110 consistently demonstrates its antitumor efficacy among prostate cancer patients with T878X and H875Y mutations [39].

8. ir.arvinas.com ir.arvinas.com/news-releases/news-release-details/arvinas-announces-updated-phase-1-data-demonstrating-clinical

Press Release Details Arvinas Announces Updated Phase 1 Data Demonstrating Clinical Activity of PROTAC® Protein Degrader ARV-110 in Patients with Refractory Prostate ...

9. urotoday.com urotoday.com/conference-highlights/asco-gu-2022/asco-gu-2022-prostate-cancer/135417-asco-gu-2022-phase-1-2-study-of-arv-110-an-androgen-receptor-ar-protac-degrader-in-metastatic-castration-resistant-prostate-cancer-mcrpc.html

ASCO GU 2022: Phase 1/2 Study of ARV-110 ... Dr. Gao presented results of a phase 1/2 study examining the role of ARV-110 in metastatic castration-resistant prostate cancer (mCRPC).