Abivertinib + Abiraterone for Prostate Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of combining abivertinib with abiraterone (also known as Zytiga or Yonsa) for individuals with metastatic castration-resistant prostate cancer, a type that resists standard hormone treatments. The trial includes two groups: one that hasn't used abiraterone before and another where the cancer progresses despite abiraterone treatment. Researchers aim to determine if adding abivertinib can better manage the disease. Suitable participants have prostate cancer that has spread, does not respond to hormone therapy, and possess a genetic marker called HSD3B1. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that abivertinib has potential as a treatment for certain types of lung cancer. Most patients tolerated it well. Some side effects were reported, but they were not severe for most people. Researchers are closely monitoring its safety.

For abiraterone, already approved for prostate cancer, more information is available. Common side effects include tiredness, joint pain, and high blood pressure, which are usually manageable. However, it can also cause more serious issues like heart problems in some cases. Since the FDA has approved abiraterone for this type of cancer, its safety is well-documented.

Both treatments have advantages and disadvantages. It's important to consider these when thinking about joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Abivertinib and Abiraterone because it targets prostate cancer in a unique way. Unlike standard treatments like chemotherapy or hormone therapies, Abivertinib is a novel tyrosine kinase inhibitor that can potentially enhance the effects of Abiraterone, a drug that blocks androgen production. This combination aims to more effectively tackle cancer cells that have become resistant to traditional hormone therapy. By targeting cancer's growth pathways more precisely, this duo could offer new hope for patients with metastatic castration-resistant prostate cancer.

What evidence suggests that this trial's treatments could be effective for metastatic castration-resistant prostate cancer?

Research has shown that abiraterone effectively treats advanced prostate cancer that no longer responds to hormone therapy. Studies found that patients taking abiraterone with prednisone experienced significant improvements. This trial examines the combination of abivertinib and abiraterone to determine if it can further benefit patients. Participants will be divided into two groups: abiraterone-naive and abiraterone-progressing. While the mechanism of these drugs offers hope, the full benefits of this combination remain under investigation. ^{6 7 8 9}

Who Is on the Research Team?

Mike Royal, MD

Principal Investigator

Sorrento Therapeutics, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• Abivertinib

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. urologytimes.com urologytimes.com/view/trial-to-evaluate-tki-and-abiraterone-treatment-combination-for-prostate-cancer

Trial to evaluate TKI and abiraterone treatment ... A phase 2, open-label clinical trial (NCT05361915) to evaluate the efficacy of a new prostate cancer treatment combination of abivertinib and abiraterone ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11560831/

Efficacy of abiraterone combined with prednisone in ... In the treatment of castration-resistant prostate cancer, the combination of abiraterone and prednisone in the treated group demonstrated superior efficacy ...

3. ngdc.cncb.ac.cn ngdc.cncb.ac.cn/openlb/publication/OLB-PM-32892496

Efficacy of abiraterone acetate in castration-resistant ... PURPOSE: The aim of this study was to evaluate the efficacy of abiraterone in patients with castration-resistant metastatic prostate cancer. MATERIALS AND ...

4. oncnursingnews.com oncnursingnews.com/view/a-first-time-comparison-reveals-the-efficacy-of-abiraterone-acetate-compared-with-enzalutamide-in-prostate-cancer

A First-Time Comparison Reveals the Efficacy of ... The purpose of this study was to compare clinical outcomes of patients with metastatic castration-resistant prostate cancer who were treated ...

5. yonsarx.com yonsarx.com/efficacy-and-safety

Efficacy and Safety | YONSA® (abiraterone acetate) The most common adverse reactions (≥10%) are fatigue, joint swelling or discomfort, edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, urinary ...

6. cdn.caymanchem.com cdn.caymanchem.com/cdn/msds/15148m.pdf

Safety Data Sheet Handling: · Precautions for safe handling. No special precautions are necessary if used correctly. Avoid breathing dust/fume/gas/mist/vapours/ ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/210308s000lbl.pdf

YONSA (abiraterone - accessdata.fda.gov Cardiovascular Adverse Reactions: In the combined data for studies 1 and 2, cardiac failure occurred more commonly in patients treated with abiraterone acetate ...

8. zytigahcp.com zytigahcp.com/important-safety-information/

Important Safety Information Hypokalemia, Fluid Retention, and Cardiovascular Adverse Reactions Due to Mineralocorticoid Excess - ZYTIGA® may cause hypertension, hypokalemia, and fluid ...

9. mayoclinic.org mayoclinic.org/drugs-supplements/abiraterone-oral-route/description/drg-20074889

Abiraterone (oral route) - Side effects & dosage This medicine may also cause birth defects if the father is using it when his sexual partner becomes pregnant. You must use a condom and another ...