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

A Phase 1b Open-Label, Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ARV-110 in Combination With Abiraterone in Patients With Metastatic Prostate Cancer

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer Metastatic
• Intervention / Treatment: Drug: Bavdegalutamide; Drug: Abiraterone

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Clinical Trial Site
  • Ontario
    • Toronto, Ontario, Canada
      • Clinical Trial Site
  • Quebec
    • Montreal, Quebec, Canada
      • Clinical Trial Site
• France
  • Caen, France
    • Clinical Trial Site
  • Paris, France
    • Clinical Trial Site
  • Villejuif, France
    • Clinical Trial Site
• United Kingdom
  • Preston, United Kingdom, PR2 9HT
    • Clinical Trial Site
  • England
    • London, England, United Kingdom
      • Clinical Trial Site
  • Wales
    • Cardiff, Wales, United Kingdom
      • Clinical Trial Site
• United States
  • California
    • Santa Monica, California, United States, 91361
      • Clinical Trial Site
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Clinical Trial Site
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Clinical Trial Site
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Clinical Trial Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Clinical Trial Site
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Clinical Trial Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Clinical Trial Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histological, pathological, or cytological confirmed diagnosis of adenocarcinoma of the prostate.
2. 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).

3. Recent Prostate-specific antigen (PSA) values must demonstrate:

   1. Rising PSAs at least 16 weeks after initiation of abiraterone
   2. 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.
4. 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.
5. Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or inhibitor, or orchiectomy (surgical or medical castration).
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

1. Previously treated with enzalutamide, apalutamide, darolutamide or experimental therapies (e.g., protein degraders or inhibitors) directed at the androgen receptor.
2. 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.
3. Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow.
4. 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.
5. Major surgery (as judged by the Investigator) within 4 weeks of first dose of study drug.
6. Untreated brain metastases or brain metastases requiring steroids
7. 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.
8. 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.
9. 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).
10. Hypertension that cannot be controlled by medications (>150/90 millimeters of mercury [mmHg] despite optimal medical therapy).
11. 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.
12. 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.
13. Participants with Child Pugh C.
14. Participants with electrolyte imbalances of hypokalemia, hypomagnesemia, and/or hypocalcemia.
15. Participants with QTcF ≥470 millisecond (msec).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bavdegalutamide + Abiraterone (Safety Lead-in); 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; Bavdegalutamide oral tablets daily in 28 day cycles.; Other Names: ARV-110; Drug: Abiraterone; 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.
Experimental: Bavdegalutamide + Abiraterone (Expansion Phase); 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; Bavdegalutamide oral tablets daily in 28 day cycles.; Other Names: ARV-110; Drug: Abiraterone; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Lead-in: Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of Bavdegalutamide and Abiraterone	AUCtau is defined as area under the concentration-time curve during a dosing interval.	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	AUClast is defined as area under the concentration-time curve from time 0 through the last measurable concentration (AUClast).	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	Cmax is the maximum observed plasma concentration.	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	Cmin is the minimum observed plasma concentration.	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	Tmax is the time of maximum observed plasma concentration.	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: Last Measurable Plasma Concentration (Clast) of Bavdegalutamide and Abiraterone	Clast is the last measurable plasma concentration.	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 Last Measurable Plasma Concentration (Tlast) of Bavdegalutamide and Abiraterone	Tlast is the time of last measurable plasma concentration.	Pre-dose, 1, 2, 4, 6 and 8 hours post dose on Cycle 1 Day 21 (each cycle is of 28 days)
Percentage of Participants With Lack of Prostate-Specific Antigen (PSA) Progression	PSA control rate was defined as the percentage of participants with lack of PSA progression at 12 weeks. PSA progression was defined as a >=25% increase in PSA and an absolute increase in PSA of >=2 nanograms per milliliter (ng/mL) above the nadir, which was confirmed by a second consecutive value obtained 3 or more weeks later.	Baseline (Day 1) up to 12 weeks
PSA30 Response Rate	A PSA30 response rate was the percentage of participants with a PSA30 response. A PSA30 response was defined as a >=30% decline in PSA from baseline. This decline must have been confirmed to be sustained by a second PSA performed >=3 weeks later. Baseline was defined as the last available observation prior to or on the first administration of bavdegalutamide and on study abiraterone.	Baseline up to approximately 152 weeks
PSA50 Response Rate	A PSA50 response rate was the percentage of participants with a PSA50 response. A PSA50 response was defined as a >=50% decline in PSA from baseline. This decline must have been confirmed to be sustained by a second PSA performed >=3 weeks later. Baseline was defined as the last available observation prior to or on the first administration of bavdegalutamide and on study abiraterone.	Baseline up to approximately 152 weeks
Duration of PSA30 Response	Duration of PSA30 response was the time interval from the date of the first confirmed PSA30 response to the date of confirmed PSA progression. Participants who did not have PSA progression were to be censored on the date of the last PSA assessment before receipt of new subsequent anticancer therapy. A PSA30 response was defined as a >=30% decline in PSA from baseline. This decline must have been confirmed to be sustained by a second PSA performed >=3 weeks later. PSA progression was defined as a >=25% increase in PSA and an absolute increase in PSA of >=2 ng/mL above the nadir, which was confirmed by a second consecutive value obtained 3 or more weeks later. Baseline was defined as the last available observation prior to or on the first administration of bavdegalutamide and on study abiraterone. Kaplan-Meier estimates were used for analysis.	From the date of the first confirmed PSA30 response up to confirmed PSA progression (assessed up to approximately 152 weeks)
Duration of PSA50 Response	Duration of PSA50 response was the time interval from the date of the first confirmed PSA50 response to the date of confirmed PSA progression. Participants who did not have PSA progression were to be censored on the date of the last PSA assessment before receipt of new subsequent anticancer therapy. A PSA50 response was defined as a >=50% decline in PSA from baseline. This decline must have been confirmed to be sustained by a second PSA performed >=3 weeks later. PSA progression was defined as a >=25% increase in PSA and an absolute increase in PSA of >=2 ng/mL above the nadir, which was confirmed by a second consecutive value obtained 3 or more weeks later. Baseline was defined as the last available observation prior to or on the first administration of bavdegalutamide and on study abiraterone. Kaplan-Meier estimates were used for analysis.	From the date of the first confirmed PSA50 response up to confirmed PSA progression (assessed up to approximately 152 weeks)
Time to PSA Progression	Time to PSA progression was the time interval from the date of the first study dose to the date of PSA progression. The PSA progression date was defined as the date that a >=25% increase and an absolute increase of >=2 ng/mL above the nadir was documented, which was confirmed by a second consecutive value obtained >=3 weeks later. Participants who did not have PSA progression were to be censored on the date of the last PSA assessment before receipt of new anticancer therapy. If a participant did not have a postbaseline PSA, they were to be censored on the date of the first study dose. Kaplan-Meier estimates were used for analysis.	From first dose up to date of PSA progression (assessed up to approximately 152 weeks)
Radiographic Progression-Free Survival (rPFS)	rPFS was defined as the time interval from the date of the first study dose to the date of first progression per modified Response Evaluation Criteria in Solid Tumors 1.1 (RECIST v1.1)/Prostate Cancer Working Group 3 (PCWG3) Criteria, or death from any cause, whichever occurred first. Radiological progression was defined by either soft tissue tumor progression defined by RECIST v1.1, or bone progression defined by PCWG2. Bone progression was defined as a minimum of two new lesions. Progression on bone scans before or at week 8 required a confirmatory scan performed 6 or more weeks later. rPFS was analyzed using Kaplan-Meier methodology. Participants who were alive and whose disease did not progress were to be censored on the date of the last disease assessment before receipt of new anticancer therapy. If the participant was alive and did not have post baseline imaging assessment, participant was to be censored on the date of the first study drug dose.	From first dose to the date of first progression (assessed up to approximately 152 weeks)
Overall Response Rate (ORR) by Modified RECIST v1.1)/PCWG3 Criteria	ORR was defined as the percentage of participants whose best overall response was a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator according to modified RECIST v1.1/PCWG3. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm) and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions.	From first dose up to approximately 152 weeks
Duration of Radiographic Response (DOR)	DOR was defined as the time interval from the date of first documented confirmed CR/PR to the date of the first documented tumor progression (per modified RECIST 1.1/PCWG3 criteria), or death, whichever occurred first. CR was defined as complete disappearance of all target lesions and non-target disease and no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease and no new lesions. Radiological progression was defined by either soft tissue tumor progression defined by RECIST v1.1, or bone progression defined by PCWG2. Bone progression was defined as a minimum of two new lesions. Progression on bone scans before or at week 8 required a confirmatory scan performed 6 or more weeks later.	From the date of first documented confirmed response to the date of the first documented tumor progression (assessed up to approximately 152 weeks)

Collaborators and Investigators

• Sponsor: Arvinas Androgen Receptor, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2022
• Primary Completion (Actual): July 2, 2024
• Study Completion (Actual): April 10, 2025

Study Registration Dates

• First Submitted: November 19, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prostate Cancer; mCRPC; Metastatic Prostate Cancer; Castrate-Resistant; bavdegalutamide
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; abiraterone
• Other Study ID Numbers: ARV-110-mCRPC-103; 2021-003046-21 (EudraCT Number); 2024-516661-37-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No