Trial Outcomes & Findings for Abemaciclib (LY2835219) in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer (NCT NCT04408924)

Last Updated: 2024-06-25

Results Overview

ORR is defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) in soft tissue per response evaluation criteria in solid tumors (RECIST) version 1.1 and do not have concurrent bone progression per Prostate Cancer Clinical Trials Working Group 3 (PCWG3), as assessed by the investigator. ORR = (participants with confirmed CR and no bone progression) + (participants with confirmed PR and no bone progression) x 100 / all treated participants.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

44 participants

Primary outcome timeframe

From Date of First Dose until Objective Progression (Up To 12.8 Months)

Results posted on

2024-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	200 Milligram (mg) Abemaciclib Twice Daily Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Overall Study STARTED	44
Overall Study Received at Least One Dose of Study Drug	44
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	13

Reasons for withdrawal

Reasons for withdrawal
Measure	200 Milligram (mg) Abemaciclib Twice Daily Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Overall Study Off Treatment on Post-Treatment-Discontinuation Follow-up	3
Overall Study Lost to Follow-up	3
Overall Study Withdrawal by Subject	5
Overall Study Sponsor Decision	2

Baseline Characteristics

Abemaciclib (LY2835219) in Men With Heavily Treated Metastatic Castration-Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	200 mg Abemaciclib Twice Daily n=44 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Age, Continuous	68.3 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	41 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants
Region of Enrollment France	14 participants n=5 Participants
Region of Enrollment Spain	27 participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: From Date of First Dose until Objective Progression (Up To 12.8 Months)

Population: All participants who received at least one dose of the study drug.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=44 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Percentage of Participants With Confirmed Objective Response (Objective Response Rate [ORR])	6.8 percentage of participants Interval 0.0 to 14.3

SECONDARY outcome

Timeframe: From Date of First Dose until Objective Progression or Death from Any Cause (Up To 12.8 Months)

Population: All participants who received at least one dose of the study drug. Participants censored = 11.

The rPFS time is measured from the date of first dose to the earliest date of investigator-assessed radiographic progression per RECIST 1.1 for soft tissue and PCWG3 criteria for bone, or death from any cause, whichever occurred first. Participants who have neither progressed nor died will be censored at the day of their last radiographic tumor assessment (if available) or date of first dose if no post initiation (i.e., postbaseline) radiographic assessment is available.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=44 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Radiographic Progression-Free Survival (rPFS)	2.7 months Interval 1.9 to 3.7

SECONDARY outcome

Timeframe: From Date of First Dose until Date of Death from Any Cause (Up To 28 Months)

Population: All participants who received at least one dose of the study drug. Participants censored = 13.

OS time is measured from the date of first dose 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	200 mg Abemaciclib Twice Daily n=44 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Overall Survival (OS)	8.38 months Interval 5.62 to 12.69

SECONDARY outcome

Timeframe: CR or PR to Disease Progression or Death Due to Any Cause (Up to 12 Months)

Population: All randomized participants who received at least one dose of the study drug and had CR or PR responses. The median was not achieved due to insufficient sample data.

DoR is measured only for confirmed responders (participants with a confirmed soft tissue best overall response of CR or PR per RECIST 1.1 no concurrent bone progression per PCWG3). It is measured from the date of first evidence of soft tissue CR or PR to the earliest date of investigator-assessed radiographic progression or death from any cause, whichever is earlier.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=3 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Duration of Response (DoR)	NA months Interval 3.88 to 11.18 Median was not achieved due to insufficient sample data.

SECONDARY outcome

Timeframe: From Date of First Dose until Measured Progressive Disease or Death Due to Any Cause (Up To 12.8 Months)

Population: All participants who received at least one dose of the study drug.

The DCR is defined as the percentage of participants with confirmed soft tissue best overall response of CR, PR, or stable disease (SD) per RECIST 1.1, and do not have concurrent bone disease progression per PCWG3.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=44 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR])	45.5 percentage of participants Interval 30.7 to 60.2

SECONDARY outcome

Timeframe: From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months)

Population: All participants who received at least one dose of the study drug. Participants censored = 31.

Time to PSA progression is defined as the time from the date of treatment initiation to the date of first observation of PSA progression. 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	200 mg Abemaciclib Twice Daily n=44 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Time to Prostate-Specific Antigen (PSA) Progression	6.5 months Interval 3.2 to The upper 95% confidence interval (CI) not achieved as there were insufficient number of events due to high censoring rate.

SECONDARY outcome

Timeframe: From Date of First Dose until Confirmed PSA Progression (Up To 12.8 Months)

Population: All participants who received at least one dose of the study drug.

The PSA response rate is defined as the percentage of participants with a reduction in PSA level ≥50% from baseline, confirmed with a second assessment conducted at least 3 weeks later.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=44 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Percentage of Participants Who Achieved Prostate-Specific Antigen (PSA) Response (PSA Response Rate)	4.6 percentage of participants

SECONDARY outcome

Timeframe: From Date of First Dose until Symptomatic Progression (Up to 12.8 Months)

Population: All participants who received at least one dose of the study drug. Participants censored = 28.

Time to symptomatic progression is defined as the time from first dose to any of the following (whichever occurred earlier): 1) symptomatic skeletal event, 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 anticancer therapy; and 3) development of clinically significant symptoms due to locoregional tumor progression requiring surgical intervention or radiation therapy. For participants who were not known to have symptomatic progression at the time of data analysis, data were censored on the last date at which no symptomatic progression was indicated.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=44 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Time to Symptomatic Progression	4.1 months Interval 3.7 to Upper 95% confidence interval (CI) was not achieved due to high censoring rate.

SECONDARY outcome

Timeframe: Cycle (C) 1 Day (D) 1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose

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

PK: Cmax,ss of abemaciclib is reported. The cycle length was 28 days.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=43 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Pharmacokinetics (PK): Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib	223 nanogram per milliliter (ng/ mL) Geometric Coefficient of Variation 47

SECONDARY outcome

Timeframe: C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose

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

PK: Cmin,ss of abemaciclib is reported.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=43 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib	176 ng/mL Geometric Coefficient of Variation 37

SECONDARY outcome

Timeframe: C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose

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

PK: Cmax,ss of abemaciclib metabolites (Total Active Species) is reported.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=43 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
PK: Maximum Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib Metabolites (Total Active Species)	1.7 micromolar per liter (µmol/L) Geometric Coefficient of Variation 79

SECONDARY outcome

Timeframe: C1 D1: Post dose; C1 D15, C2D1, C2D15, C3D1: Pre dose

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

PK: Cmin,ss of abemaciclib metabolites (Total Active Species) is reported.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=43 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
PK: Minimum/Trough Concentration at Steady State (Cmin,ss) of Abemaciclib Metabolites (Total Active Species)	1.5 µmol/L Geometric Coefficient of Variation 80

SECONDARY outcome

Timeframe: Baseline

Population: All participants with evaluable tumor tissue specimens

Percentage of participants with expression of Ki-67 proliferation marker at baseline by immunohistochemistry. Baseline expression of the Ki-67 proliferation marker was evaluated by IHC utilizing a 20% or higher score to define high Ki-67 expression. The percentage of Ki-67 positive cells was defined by the number of non-apoptotic tumor cells with unequivocal brown nuclear staining (intensities ≥1 using a 0-3 scale) over the total number of non-apoptotic tumor cells. Unit of Measure is percentage of participants with low or high baseline Ki-67 expression.

Outcome measures

Outcome measures
Measure	200 mg Abemaciclib Twice Daily n=31 Participants Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Percentage of Participants With Expression of Ki-67 Proliferation Marker by Immunohistochemistry (IHC) Low baseline Ki-67 expression	25.8 Percentage of participants
Percentage of Participants With Expression of Ki-67 Proliferation Marker by Immunohistochemistry (IHC) High baseline Ki-67 expression	74.2 Percentage of participants

Adverse Events

200 mg Abemaciclib Twice Daily

Serious events: 18 serious events

Other events: 42 other events

Deaths: 31 deaths

Serious adverse events

Serious adverse events
Measure	200 mg Abemaciclib Twice Daily n=44 participants at risk Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Blood and lymphatic system disorders Anaemia	4.5% 2/44 • Number of events 2 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Cardiac disorders Myocardial infarction	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Eye disorders Diplopia	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Gastrointestinal disorders Diarrhoea	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Gastrointestinal disorders Haemoperitoneum	2.3% 1/44 • Number of events 2 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
General disorders General physical health deterioration	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
General disorders Pain	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
General disorders Pyrexia	6.8% 3/44 • Number of events 4 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Infections and infestations Bacteraemia	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Infections and infestations Cellulitis	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Infections and infestations Sepsis	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Infections and infestations Urinary tract infection	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Injury, poisoning and procedural complications Periprosthetic fracture	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Injury, poisoning and procedural complications Subdural haematoma	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Injury, poisoning and procedural complications Subdural haemorrhage	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Investigations Blood creatinine increased	4.5% 2/44 • Number of events 2 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Nervous system disorders Cerebrovascular accident	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Product Issues Device occlusion	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Renal and urinary disorders Renal failure	6.8% 3/44 • Number of events 3 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Renal and urinary disorders Urinary retention	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Skin and subcutaneous tissue disorders Dermatitis	2.3% 1/44 • Number of events 1 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.

Other adverse events

Other adverse events
Measure	200 mg Abemaciclib Twice Daily n=44 participants at risk Participants received 200 mg abemaciclib administered orally twice daily on a continuous dosing schedule (28-day cycle) until symptomatic and/or radiographic progression, unacceptable toxicity, or until another discontinuation criterion is met.
Blood and lymphatic system disorders Anaemia	36.4% 16/44 • Number of events 17 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Blood and lymphatic system disorders Neutropenia	29.5% 13/44 • Number of events 18 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Blood and lymphatic system disorders Thrombocytopenia	9.1% 4/44 • Number of events 4 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Gastrointestinal disorders Abdominal pain	11.4% 5/44 • Number of events 7 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Gastrointestinal disorders Constipation	20.5% 9/44 • Number of events 11 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Gastrointestinal disorders Diarrhoea	81.8% 36/44 • Number of events 57 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Gastrointestinal disorders Nausea	47.7% 21/44 • Number of events 28 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Gastrointestinal disorders Vomiting	36.4% 16/44 • Number of events 19 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
General disorders Asthenia	54.5% 24/44 • Number of events 34 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
General disorders Fatigue	11.4% 5/44 • Number of events 5 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
General disorders Oedema peripheral	13.6% 6/44 • Number of events 6 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
General disorders Pyrexia	13.6% 6/44 • Number of events 6 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Infections and infestations Urinary tract infection	6.8% 3/44 • Number of events 4 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Investigations Blood creatinine increased	15.9% 7/44 • Number of events 9 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Investigations Neutrophil count decreased	9.1% 4/44 • Number of events 4 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Investigations Platelet count decreased	11.4% 5/44 • Number of events 6 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Investigations Weight decreased	6.8% 3/44 • Number of events 3 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Metabolism and nutrition disorders Decreased appetite	54.5% 24/44 • Number of events 25 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Musculoskeletal and connective tissue disorders Arthralgia	11.4% 5/44 • Number of events 6 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Musculoskeletal and connective tissue disorders Back pain	15.9% 7/44 • Number of events 7 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.8% 3/44 • Number of events 3 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Nervous system disorders Dysgeusia	6.8% 3/44 • Number of events 4 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Psychiatric disorders Insomnia	6.8% 3/44 • Number of events 3 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Renal and urinary disorders Haematuria	6.8% 3/44 • Number of events 4 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Respiratory, thoracic and mediastinal disorders Cough	6.8% 3/44 • Number of events 3 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.8% 3/44 • Number of events 3 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.
Skin and subcutaneous tissue disorders Dry skin	6.8% 3/44 • Number of events 3 • Baseline Up to 28 Months All participants who received at least one dose of the study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60