Trial Outcomes & Findings for A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer (NCT NCT03706365)

Last Updated: 2025-04-20

Results Overview

The rPFS time is measured from the date of randomization to the earliest date of investigator determined radiographic disease progression (by objective radiographic disease assessment per response evaluation criteria in solid tumors (RECIST) version 1.1 for soft tissue AND/OR radionuclide bone scan using prostate cancer working group 3 -PCWG3 criteria for bone) or death from any cause, whichever occurs first.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2/PHASE3

Target enrollment

393 participants

Primary outcome timeframe

From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (Up to 60 Months)

Results posted on

2025-04-20

Participant Flow

Participant milestones

Participant milestones
Measure	Abemaciclib Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Overall Study STARTED	206	187
Overall Study Received at Least One Dose of Study Drug	206	185
Overall Study COMPLETED	131	121
Overall Study NOT COMPLETED	75	66

Reasons for withdrawal

Reasons for withdrawal
Measure	Abemaciclib Participants received 200 milligram (mg) abemaciclib twice daily (BID) in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Overall Study Lost to Follow-up	7	0
Overall Study Withdrawal by Subject	17	15
Overall Study On Study Treatment	51	51

Baseline Characteristics

A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abemaciclib n=206 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=187 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Total n=393 Participants Total of all reporting groups
Age, Continuous	68.70 years STANDARD_DEVIATION 8.57 • n=93 Participants	69.60 years STANDARD_DEVIATION 8.81 • n=4 Participants	69.10 years STANDARD_DEVIATION 8.69 • n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	206 Participants n=93 Participants	187 Participants n=4 Participants	393 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=93 Participants	7 Participants n=4 Participants	20 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	186 Participants n=93 Participants	174 Participants n=4 Participants	360 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=93 Participants	6 Participants n=4 Participants	13 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	35 Participants n=93 Participants	45 Participants n=4 Participants	80 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	7 Participants n=93 Participants	10 Participants n=4 Participants	17 Participants n=27 Participants
Race (NIH/OMB) White	161 Participants n=93 Participants	128 Participants n=4 Participants	289 Participants n=27 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	4 Participants n=4 Participants	6 Participants n=27 Participants
Region of Enrollment Australia	17 participants n=93 Participants	18 participants n=4 Participants	35 participants n=27 Participants
Region of Enrollment China	4 participants n=93 Participants	9 participants n=4 Participants	13 participants n=27 Participants
Region of Enrollment Denmark	7 participants n=93 Participants	10 participants n=4 Participants	17 participants n=27 Participants
Region of Enrollment France	4 participants n=93 Participants	5 participants n=4 Participants	9 participants n=27 Participants
Region of Enrollment Germany	23 participants n=93 Participants	16 participants n=4 Participants	39 participants n=27 Participants
Region of Enrollment Japan	15 participants n=93 Participants	18 participants n=4 Participants	33 participants n=27 Participants
Region of Enrollment Netherlands	7 participants n=93 Participants	8 participants n=4 Participants	15 participants n=27 Participants
Region of Enrollment Romania	10 participants n=93 Participants	7 participants n=4 Participants	17 participants n=27 Participants
Region of Enrollment South Korea	14 participants n=93 Participants	17 participants n=4 Participants	31 participants n=27 Participants
Region of Enrollment Spain	45 participants n=93 Participants	30 participants n=4 Participants	75 participants n=27 Participants
Region of Enrollment United Kingdom	11 participants n=93 Participants	9 participants n=4 Participants	20 participants n=27 Participants
Region of Enrollment United States	49 participants n=93 Participants	40 participants n=4 Participants	89 participants n=27 Participants

PRIMARY outcome

Timeframe: From Date of Randomization to Radiographic Disease Progression or Death from Any Cause (Up to 60 Months)

Population: All randomized participants. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

Outcome measures

Outcome measures
Measure	Abemaciclib n=206 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=187 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Radiographic Progression Free Survival (rPFS)	21.96 Months Interval 19.33 to 27.48	20.28 Months Interval 16.47 to 24.36

SECONDARY outcome

Timeframe: From Date of Randomization to the Date of the First Observation of PSA Progression (Up to 60 Months)

Population: All randomized participants. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

The PSA progression is defined as a greater than or equal to (\>=) 25 percentage (%) increase and an absolute increase of \>=2 nanogram/milliliter (ng/mL) above the nadir (or baseline value if baseline is the smallest on study), which is confirmed by a second value obtained 3 or more weeks later.

Outcome measures

Outcome measures
Measure	Abemaciclib n=206 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=187 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Time to Prostate-Specific Antigen (PSA) Progression	22.19 Months Interval 15.68 to 33.17	16.60 Months Interval 12.03 to 20.28

SECONDARY outcome

Timeframe: From Date of Randomization Until Radiographic Disease Progression or Death from Any Cause (Up to 60 Months)

Population: All randomized participants. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

rPFS is defined as the time from the date of randomization to the earliest date of radiographic disease progression determined by blinded independent central review (BICR) or death from any cause, whichever occurs first.

Outcome measures

Outcome measures
Measure	Abemaciclib n=206 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=187 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Radiographic Progression Free Survival (rPFS) Determined by Blinded Independent Central Review	24.89 Months Interval 21.96 to Upper limit of 95% confidence interval was not achieved due to insufficient sample data.	22.88 Months Interval 19.36 to 31.5

SECONDARY outcome

Timeframe: Baseline to Radiographic Disease Progression (Up to 60 Months)

Population: All randomized participants who received at least one dose of the study drug and had CR or PR responses.

ORR is a summary measure of best overall response (BOR) as defined by RECIST 1.1 for soft tissue per investigator assessment. BOR is derived from time point responses. All time point responses observed while on study treatment and during the short-term follow-up period (but before the initiation of post-discontinuation systemic anticancer therapy) will be included in the derivation. Each patient's BOR will be categorized as complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or not evaluable (NE). A BOR of CR or PR will require confirmation, but sensitivity analyses of response-based endpoints may be performed where confirmation of a BOR of CR or PR is not required.

Outcome measures

Outcome measures
Measure	Abemaciclib n=84 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=73 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)	45.2 percentage of participants Interval 34.6 to 55.9	54.8 percentage of participants Interval 43.4 to 66.2

SECONDARY outcome

Timeframe: Date of First Documented CR or PR to Date of Radiographic Disease Progression or Death from Any Cause (Up to 60 Months)

Population: All randomized participants who received at least one dose of the study drug and had CR or PR responses with objective response.

The DoR time is defined only for responders (participants with a soft tissue BOR of CR or PR) in the measurable disease population. It is measured from the date of first evidence of soft tissue CR or PR to the earliest date of investigator determined radiographic disease progression or death from any cause, whichever is earlier.

Outcome measures

Outcome measures
Measure	Abemaciclib n=38 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=40 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Duration of Response (DOR)	21.27 Months Interval 16.6 to Upper limit of 95% confidence interval was not achieved due to insufficient sample data.	15.68 Months Interval 11.87 to 39.35

SECONDARY outcome

Timeframe: From Date of Randomization to Date of Death Due to Any Cause (Up to 60 Months)

Population: All randomized participants. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

The OS time is measured from the date of randomization to the date of death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data were censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	Abemaciclib n=206 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=187 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Overall Survival (OS)	38.01 Months Interval 30.58 to 46.65	33.21 Months Interval 29.52 to Upper limit of 95% confidence interval was not achieved due to insufficient sample data.

SECONDARY outcome

Timeframe: From Randomization to the Date of the First Documented Symptomatic Progression (Up to 60 Months)

Population: All randomized participants. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

Time to symptomatic progression is defined as the time from randomization to any of the following (whichever occurs earlier): 1. Symptomatic Skeletal Event (SSE), defined as symptomatic fracture, surgery or radiation to bone, or spinal cord compression. 2. Pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy. 3. Development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy.

Outcome measures

Outcome measures
Measure	Abemaciclib n=206 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=187 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Time to Symptomatic Progression	51.39 Months Interval 27.98 to Upper limit of 95% confidence interval was not achieved due to high censoring rate.	35.74 Months Interval 28.44 to Upper limit of 95% confidence interval was not achieved due to high censoring rate.

SECONDARY outcome

Timeframe: Cycle (C) 1 Day (D) 1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle)

Population: All participants who received at least one dose of study drug had evaluable PK data.

PK: Mean steady state exposure of abemaciclib.

Outcome measures

Outcome measures
Measure	Abemaciclib n=170 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib C1 D1	4.79 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 157	—
Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib C1 D15	289 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 58.7	—
Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib C2 D1	253 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 65.7	—
Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib C2 D15	252 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 68.4	—
Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib C3 D1	270 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 54.5	—

SECONDARY outcome

Timeframe: C1 D1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle)

Population: All participants who received at least one dose of study drug had evaluable PK data.

PK: Mean steady state exposure of abemaciclib metabolite LSN2839567.

Outcome measures

Outcome measures
Measure	Abemaciclib n=170 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 C2 D1	112 ng/mL Geometric Coefficient of Variation 50.1	—
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 C1 D1	2.90 ng/mL Geometric Coefficient of Variation 87.4	—
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 C1 D15	125 ng/mL Geometric Coefficient of Variation 50.4	—
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 C2 D15	116 ng/mL Geometric Coefficient of Variation 51.0	—
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN2839567 C3 D1	110 ng/mL Geometric Coefficient of Variation 62.2	—

SECONDARY outcome

Timeframe: C1 D1: Predose, 30 min post-dose; C1 D15, C2 D1, C2 D15, C3 D1: Post dose (28 Days Cycle)

Population: All participants who received at least one dose of study drug had evaluable PK data.

PK: Mean steady state exposure of abemaciclib metabolite LSN3106726.

Outcome measures

Outcome measures
Measure	Abemaciclib n=170 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 C1 D1	2.80 ng/mL Geometric Coefficient of Variation 77.7	—
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 C1 D15	195 ng/mL Geometric Coefficient of Variation 43.0	—
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 C2 D1	174 ng/mL Geometric Coefficient of Variation 42.8	—
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 C2 D15	174 ng/mL Geometric Coefficient of Variation 44.1	—
PK: Mean Steady State Exposure of Abemaciclib Metabolite LSN3106726 C3 D1	176 ng/mL Geometric Coefficient of Variation 36.4	—

SECONDARY outcome

Timeframe: C1 D15, Post dose

Population: All participants who received at least one dose of study drug had evaluable PK data.

PK: Mean Steady State Exposure of Abiraterone Acetate.

Outcome measures

Outcome measures
Measure	Abemaciclib n=189 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=175 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
PK: Mean Steady State Exposure of Abiraterone Acetate	45.2 ng/mL Geometric Coefficient of Variation 175	40.0 ng/mL Geometric Coefficient of Variation 203

SECONDARY outcome

Timeframe: From Randomization Through Follow-up (Up to 60 months)

Population: All randomized participants. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

Time to Worst Pain Progression defined as the time from randomization to any of the following (whichever occurs earlier): For participants without opioid use at baseline (World Health Organization-Analgesic Ladder-WHO-AL ≤ 2):- Worst pain progression (an increase of 2 points from baseline on the Worst Pain Numeric Rating Scale (NRS) item on 2 consecutive evaluations), Initiation of weak or strong opioids (WHO-AL ≥ 3); For participants with weak or strong opioid use at baseline (WHO-AL ≥ 3): Worst pain progression (an increase of 2 points from baseline on the Worst Pain NRS item on 2 consecutive evaluations) without concurrent decreased opioid use (a decrease in WHO-AL of 1 or more) -Increased opioid use (an increase in WHO-AL of 1 or more).

Outcome measures

Outcome measures
Measure	Abemaciclib n=206 Participants Participants received 200 mg abemaciclib BID in combination with standard doses of 1000 mg abiraterone acetate once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.	Placebo n=187 Participants Participants received placebo BID in combination with standard doses of 1000 mg abiraterone once daily and 5 mg prednisone BID administered orally on a continuous dosing schedule on days 1 through 28 of a 28-day cycle until radiographic and/or symptomatic progression or until another discontinuation criterion is met.
Time to Worst Pain Progression	41.49 Months Interval 19.4 to Upper limit of 95% confidence interval was not achieved due to insufficient sample data.	24.79 Months Interval 19.17 to 31.46

Adverse Events

Abemaciclib

Serious events: 89 serious events

Other events: 204 other events

Deaths: 81 deaths

Placebo

Serious events: 66 serious events

Other events: 176 other events

Deaths: 72 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 08005455979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60