Study to Assess Abivertinib in Combination With Abiraterone in Metastatic Castration Resistant Prostate Cancer

Recruiting at 1 trial location

Overseen By Lara Rose

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sorrento Therapeutics, Inc.

Must be taking: LHRH analogues

Must not be taking: Enzalutamide, Apalutamide, Darolutamide

Disqualifiers: HIV, Hepatitis B, Brain metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, abivertinib and abiraterone, to treat prostate cancer that has spread and does not respond to typical treatments. The goal is to see if this combination can stop the cancer from growing by cutting off its fuel supply and blocking its survival routes. The study includes patients who have never taken abiraterone and those whose cancer has progressed despite taking it. Abiraterone has been used to improve overall survival in men with metastatic castration-resistant prostate cancer, but resistance to it can limit its effectiveness.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain drugs that affect liver enzymes (CYP3A inducers and inhibitors). It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Abiraterone (Zytiga, Yonsa, Abivertinib)?

Abiraterone, when used with prednisone, has been shown to significantly improve survival and delay disease progression in patients with metastatic castration-resistant prostate cancer, as demonstrated in clinical trials. ^{1 2 3 4 5}

Is abiraterone safe for humans?

Abiraterone acetate, also known as Zytiga, has been used safely in combination with prednisone for treating prostate cancer. Clinical trials have shown it to be generally safe, but like any medication, it may have side effects, so it's important to discuss with a doctor. ^{1 3 5 6 7}

How is the drug Abiraterone unique in treating prostate cancer?

Abiraterone (Zytiga) is unique because it is an oral medication that works by blocking a specific enzyme (cytochrome P450 17A1) involved in the production of male hormones, which can fuel prostate cancer growth. It is used in combination with prednisone to treat metastatic castration-resistant prostate cancer, especially in patients who have not yet received chemotherapy. ^{1 2 3 5 6}

Research Team

Mike Royal, MD

Principal Investigator

Sorrento Therapeutics, Inc.

Eligibility Criteria

Inclusion Criteria

Germline testing for HSD3B1. Confirmation of positivity for the adrenal-permissive HSD3B1(1245C) allele (germline heterozygous or homozygous) will be done centrally

Metastatic disease as identified by imaging

Progressive mCRPC as defined by: 1) castrate levels of serum testosterone < 50 ng/dL and 2) progressive disease

Exclusion Criteria

You have another type of cancer that needs to be treated, except for those that can be easily cured in one area of the body.

You have already been treated with a BTK inhibitor in the past.

Corrected QT interval calculated by the Fridericia formula per electrocardiogram within 14 days before Cycle 1 Day 1

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abivertinib in combination with abiraterone

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to approximately 63 months

Treatment Details

Interventions

• Abiraterone
• Abivertinib

Participant Groups

Group I: Abivertinib - Abiraterone-progressing Experimental Treatment 2 Interventions

Abiraterone-progressing: Abivertinib 200 mg by mouth twice daily with abiraterone 1000 mg by mouth daily.

Group II: Abivertinib - Abiraterone-naive Experimental Treatment 2 Interventions

Abiraterone-naive: Abivertinib 200 mg by mouth twice daily with abiraterone 1000 mg by mouth daily.

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?

Sorrento Therapeutics, Inc.

Lead Sponsor

Trials

48

Recruited

2,000+

Findings from Research

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]

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]

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]

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]

References

1. 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]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Comparative proteome and serum analysis identified FSCN1 as a marker of abiraterone resistance in castration-resistant prostate cancer. [2023]

5. 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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. Germany pubmed.ncbi.nlm.nih.gov

Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect. [2017]