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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Bavdegalutamide oral tablets daily in 28 day cycles.
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.
Clinical Trial Site
Santa Monica, California, United States
Clinical Trial Site
New Haven, Connecticut, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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)
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Clinical Trial Site
Fort Myers, Florida, United States
Clinical Trial Site
Boston, Massachusetts, United States
Clinical Trial Site
Columbus, Ohio, United States
Clinical Trial Site
Portland, Oregon, United States
Clinical Trial Site
Myrtle Beach, South Carolina, United States
Clinical Trial Site
Nashville, Tennessee, United States
Clinical Trial Site
Charlottesville, Virginia, United States
Clinical Trial Site
Vancouver, British Columbia, Canada
...and 8 more locations
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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From the date of first documented confirmed response to the date of the first documented tumor progression (assessed up to approximately 152 weeks)