Trial of ARV-110 and Abiraterone in Participants With Metastatic Prostate Cancer

NCT05177042 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: ARV-110-mCRPC-1032021-003046-212024-516661-37-00
• Study Type: interventional
• Target: 45
• Locations: 4 countries
• Sites: 18

Brief Summary

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

Conditions

Prostate Cancer Metastatic

Keywords

Metastatic Prostate Cancer; Prostate Cancer; Castrate-Resistant; mCRPC; bavdegalutamide

Outcome Measures

Primary Outcomes (3)

• Safety Lead-in: Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

  DLT was defined as: Grade \>=3 hematologic parameters, Grade ≥ 3 neutropenia with infection, Grade 4 neutropenia lasting \> 5 days, Febrile neutropenia, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 4 thrombocytopenia, any toxicity requiring dose interruption for \>=14 days; Grade \>=3 non-hematologic toxicities considered clinically significant and non-clinically significant Grade \>=3 toxicities requiring dose interruption for \>=10 days that determined by the investigator to be clinically relevant. Severity graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  Baseline (Day 1) up to Day 28

• Safety Lead-in: Recommended Phase 2 Dose (RP2D) of Bavdegalutamide

  Dose limiting toxicities in first 4 weeks of the study combination treatment assessed to determine the dose of bavdegalutamide associated with acceptable safety and tolerability.

  Baseline (Day 1) up to Day 28

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment Related TEAEs

  An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug, whether or not considered related to the study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE is an AE occurring on/after the date of first dose of bavdegalutamide and on-study abiraterone and within 30 days of the last dose of bavdegalutamide and on-study abiraterone. TEAEs included both Serious TEAEs and non-serious TEAEs.

  From Day 1 of study treatment in Safety lead-in up to 30 days after end of study treatment (assessed up to approximately 111.57 weeks)

Secondary Outcomes (16)

• Safety Lead-in: Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of Bavdegalutamide and Abiraterone

  Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Cycle 1 Day 21 (each cycle is of 28 days)

• Safety Lead-in: Area Under the Concentration-time Curve From Time 0 Through the Last Measurable Concentration (AUClast) of Bavdegalutamide and Abiraterone

  Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Cycle 1 Day 21 (each cycle is of 28 days)

• Safety Lead-in: Maximum Observed Plasma Concentration (Cmax) of Bavdegalutamide and Abiraterone

  Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Cycle 1 Day 21 (each cycle is of 28 days)

• Safety Lead-in: Minimum Observed Plasma Concentration (Cmin) of Bavdegalutamide and Abiraterone

  Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Cycle 1 Day 21 (each cycle is of 28 days)

• Safety Lead-in: Time of Maximum Observed Plasma Concentration (Tmax) of Bavdegalutamide and Abiraterone

  Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Cycle 1 Day 21 (each cycle is of 28 days)

Study Arms (2)

Bavdegalutamide + Abiraterone (Safety Lead-in)

EXPERIMENTAL

Male participants received 420 milligrams (mg) bavdegalutamide (3\*140 mg tablets) orally once daily with food and continued taking abiraterone orally once daily at the same dose they were taking before enrolling in the study, on an empty stomach (at least 1 hour before or 2 hours after a meal), along with a corticosteroid of the investigator's choice, per the local guidelines or product label in initial safety lead-in phase until disease progression, an adverse event (AE) leading to discontinuation of the study treatment, death, withdrawal of consent, or any criteria were met for discontinuation.

Drug: Bavdegalutamide; Drug: Abiraterone

Bavdegalutamide + Abiraterone (Expansion Phase)

EXPERIMENTAL

After the Recommended Phase 2 Dose (RP2D) was determined, additional male participants were enrolled and participants from safety lead-in phase continued to receive 420 mg bavdegalutamide (3\*140 mg tablets) orally once daily with food and continued taking abiraterone orally once daily at the same dose they were taking before enrolling in the study, on an empty stomach (at least 1 hour before or 2 hours after a meal), along with a corticosteroid of the investigator's choice, per the local guidelines or product label until disease progression, an AE leading to discontinuation of the study treatment, death, withdrawal of consent, or any criteria were met for discontinuation.

Drug: Bavdegalutamide; Drug: Abiraterone

Interventions

Bavdegalutamide DRUG

Bavdegalutamide oral tablets daily in 28 day cycles.

Also known as: ARV-110

Bavdegalutamide + Abiraterone (Expansion Phase); Bavdegalutamide + Abiraterone (Safety Lead-in)

Abiraterone DRUG

Abiraterone oral tablets daily at the same dose they were on prior to study enrollment with a concomitant corticosteroid of Investigator's choice as per local label/guidelines.

Bavdegalutamide + Abiraterone (Expansion Phase); Bavdegalutamide + Abiraterone (Safety Lead-in)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate.
• Ongoing treatment with stable doses of abiraterone (on an empty stomach) and a concomitant corticosteroid for mCRPC or for metastatic castration sensitive prostate cancer (mCSPC) until Cycle 1, Day 1 (C1D1).
• Recent Prostate-specific antigen (PSA) values must demonstrate:
• Rising PSAs at least 16 weeks after initiation of abiraterone
• At least 2 PSA values that are higher than the PSA nadir on abiraterone, measured at a minimum of 1 week apart . The screening PSA for this study may be used as the 2nd PSA value.
• No known radiographic evidence of disease progression while receiving abiraterone and clinically benefitting at the time of consent. If there is radiographic disease progression during screening, the participant may be considered eligible if, in the judgement of the investigator, the participant is clinically benefitting from abiraterone.
• Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (surgical or medical castration).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• Previously treated with enzalutamide, apalutamide, darolutamide or experimental therapies (e.g., protein degraders or inhibitors) directed at the androgen receptor.
• Treatment with any chemotherapy, investigational agents, immunotherapy, or hormonal therapy other than gonadotropin-releasing hormone (GnRH) agonists within 28 days of the start of treatment on protocol.
• Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to \>25% of the bone marrow.
• Participants taking agents that are either a) sensitive P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) substrates, or Cytochrome P450 3A4 (CYP3A4) substrates, b) P-gp, BCRP, CYP3A4, or CYP2D6 substrates that have a narrow therapeutic index, c) strong CYP3A4 inhibitors or inducers, or d) any other prohibited and/or restricted medications described in the protocol.
• Major surgery (as judged by the Investigator) within 4 weeks of first dose of study drug.
• Untreated brain metastases or brain metastases requiring steroids
• Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
• Any of the following in the previous 12 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association class II, III or IV), cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, or other clinically significant episode of thromboembolic disease.
• Any of the following in the previous 6 months: congenital long QT syndrome, Torsade de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior hemiblock (bifascicular block), or ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade ≥2, atrial fibrillation of any grade (Grade ≥2 in the case of asymptomatic lone atrial fibrillation).
• Hypertension that cannot be controlled by medications (\>150/90 millimeters of mercury \[mmHg\] despite optimal medical therapy).
• Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus, hepatitis C virus, known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness.
• Active inflammatory gastrointestinal disease, uncontrolled chronic diarrhea, known diverticular disease, or previous gastric resection or lap band surgery. Gastroesophageal reflux disease is allowed except for if under treatment with proton pump inhibitors.
• Participants with Child Pugh C.
• Participants with electrolyte imbalances of hypokalemia, hypomagnesemia, and/or hypocalcemia.
• Participants with QTcF ≥470 millisecond (msec).

Sponsors & Collaborators

• Arvinas Androgen Receptor, Inc.: lead

Study Sites (18)

Clinical Trial Site

Santa Monica, California, 91361, United States

Location

Clinical Trial Site

New Haven, Connecticut, 06519, United States

Location

Clinical Trial Site

Fort Myers, Florida, 33916, United States

Location

Clinical Trial Site

Boston, Massachusetts, 02114, United States

Location

Clinical Trial Site

Columbus, Ohio, 43210, United States

Location

Clinical Trial Site

Portland, Oregon, 97239, United States

Location

Clinical Trial Site

Myrtle Beach, South Carolina, 29572, United States

Location

Clinical Trial Site

Nashville, Tennessee, 37203, United States

Location

Clinical Trial Site

Charlottesville, Virginia, 22903, United States

Location

Clinical Trial Site

Vancouver, British Columbia, Canada

Location

Clinical Trial Site

Toronto, Ontario, Canada

Location

Clinical Trial Site

Montreal, Quebec, Canada

Location

Clinical Trial Site

Caen, France

Location

Clinical Trial Site

Paris, France

Location

Clinical Trial Site

Villejuif, France

Location

Clinical Trial Site

London, England, United Kingdom

Location

Clinical Trial Site

Cardiff, Wales, United Kingdom

Location

Clinical Trial Site

Preston, PR2 9HT, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

abiraterone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

There was no change in the safety profile between 10 September 2024 and 10 April 2025.

Results Point of Contact

• Title: Arvinas Androgen Receptor, Inc (Arvinas)
• Organization: Arvinas Androgen Receptor, Inc (Arvinas)

clinicaltrialsARV-110@arvinas.com

475-345-3354

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2021
• First Posted: January 4, 2022
• Study Start: May 13, 2022
• Primary Completion: July 2, 2024
• Study Completion: April 10, 2025
• Last Updated: April 28, 2026
• Results First Posted: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); FR (3); CA (3); GB (3)