A Study of Abemaciclib (LY2835219) in Native Chinese Participants With Advanced and/or Metastatic Cancers

A Phase 1 Study of Abemaciclib in Native Chinese Patients With Advanced and/or Metastatic Cancers

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02919696

Enrollment

Registered

2016-09-29

Start date

2017-08-07

Completion date

2019-09-03

Last updated

2020-09-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Cancer, Metastatic Cancer

Keywords

CDK4/6 Inhibitor

Brief summary

The purpose of this study is to determine the safety of the study drug known as abemaciclib in native Chinese participants with advanced and/or metastatic cancers.

Interventions

DRUGAbemaciclib

Administered orally

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* The participant must have histological or cytological evidence of cancer which is advanced and/or metastatic, and is an appropriate candidate for experimental therapy in the judgment of the investigator, after available standard therapies have ceased to provide clinical benefit. * Have the presence of measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). * Are native Chinese men or women. * Have adequate organ function, including: * Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 109/Liters (L), platelets ≥100 x 109/L, and hemoglobin ≥9 grams per deciliter. Participants may receive erythrocyte transfusions to achieve this hemoglobin level or platelet transfusions to achieve platelet levels at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day after transfusion. * Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3.0 times ULN. * Renal: Serum creatinine ≤1.2 milligrams per deciliter (mg/dL) for males or ≤1.0 mg/dL for females. * Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale. * Recovered from the acute effects of therapy (treatment- related toxicity resolved to baseline) except for residual alopecia. * Have an estimated life expectancy of ≥12 weeks.

Exclusion criteria

* Have received previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) within 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug. * Have an acute leukemia or other relevant cancers at the discretion of the investigator. * Females who are pregnant or lactating. * Participants consuming drugs or foods that are known to be inducers (for example, grapefruit juice, phenytoin, carbamazepine) or strong inhibitors of CYP3A4 should be excluded during Cycle 1. * Have history or evidence of central nervous system (CNS) malignancy or metastasis. Screening of asymptomatic participants without history of CNS metastases is not required for enrollment.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With One or More Drug Related Adverse Events	Baseline through End of Study (Up to 10 Months)	Number of participants with one or more drug related adverse events. Clinically significant events were defined as serious adverse events, regardless of causality. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

Secondary

Measure	Time frame	Description
PK: Maximum Concentration (Cmax) of Abemaciclib and Its Metabolites (Twice Daily Dosing)	Cycle 1, Day(D) 31; Predose, 1, 2, 4, 6, 8, 10, 24 Hours Postdose	PK: Maximum Concentration (Cmax) of Abemaciclib and its Metabolites following a twice daily dosing.
PK: Area Under Concentration Time Curve (AUC) From Time Zero to 12 Hours (AUC [0-12]) of Abemaciclib and Its Metabolites Single Dose	Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose	PK: Area Under Concentration Time Curve (AUC) from Time Zero to 12 hours (AUC \[0-12\]) of Abemaciclib and its Metabolites following a single oral dose.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib and Its Metabolites Single Dose	Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib and its Metabolites following a single oral dose.
PK: AUC From Time Zero to Infinity (AUC[0-inf]) of Abemaciclib and Its Metabolites Single Dose	Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose	PK: AUC from Time Zero to Infinity (AUC\[0-inf\]) of Abemaciclib and its Metabolites following a single oral dose.
Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)	Baseline to Measured Progressive Disease (Up to 13 Months )	ORR was defined as the percentage of randomized participants with a best overall response of complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Participants with unevaluable or unknown response status are considered nonresponders. Complete response (CR) is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and the 20% increase must be at least one lesion must increase by an absolute value of ≥5 mm to be considered progression.
PK: AUC From Time Zero to 12 Hours (AUC [0-12]) of Abemaciclib and Its Metabolites (Twice Daily Dosing)	Cycle 1, Day(D) 31; Predose, 1, 2, 4, 6, 8, 10, 24 Hours Postdose	PK: AUC from Time Zero to 12 hours (AUC \[0-12\]) of Abemaciclib and its Metabolites following twice daily dosing

Countries

China

Participant flow

Pre-assignment details

Participants who completed were those who had progressive disease or died due to any cause while on treatment. Pharmacokinetic (PK) samples were collected at lower doses during cycle 1.

Participants by arm

Arm	Count
Abemaciclib 150 mg Abemaciclib 150 milligram (mg) administered every 12 hours, orally, cycle 1 and then in cycle 2. Participants may continue to receive treatment until discontinuation criteria are met. One cycle is defined as 28 days. (Cycle 1: 32 days), with modifications during Cycle 1 to enable PK sampling following a single dose and repeated doses.	12
Abemaciclib 200 mg Abemaciclib 200 mg administered every 12 hours, orally, cycle 1 and then in cycle 2. Participants may continue to receive treatment until discontinuation criteria are met. One cycle is defined as 28 days. (Cycle 1: 32 days), with modifications during Cycle 1 to enable PK sampling following a single dose and repeated doses.	13
Total	25

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	2
Overall Study	Never Treated	0	1
Overall Study	Sponsor Decision	1	1
Overall Study	Withdrawal by Subject	2	1

Baseline characteristics

Characteristic	Abemaciclib 200 mg	Total	Abemaciclib 150 mg
Age, Continuous	52.00 years STANDARD_DEVIATION 8.76	53.72 years STANDARD_DEVIATION 10.1	55.58 years STANDARD_DEVIATION 11.47
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants	25 Participants	12 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	13 Participants	25 Participants	12 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants
Region of Enrollment China	13 Participants	25 Participants	12 Participants
Sex: Female, Male Female	11 Participants	22 Participants	11 Participants
Sex: Female, Male Male	2 Participants	3 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	6 / 12	1 / 13
other Total, other adverse events	12 / 12	13 / 13
serious Total, serious adverse events	2 / 12	4 / 13

Outcome results

Primary

Number of Participants With One or More Drug Related Adverse Events

Number of participants with one or more drug related adverse events. Clinically significant events were defined as serious adverse events, regardless of causality. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.

Time frame: Baseline through End of Study (Up to 10 Months)

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Abemaciclib 150 mg	Number of Participants With One or More Drug Related Adverse Events	12 Participants
Abemaciclib 200 mg	Number of Participants With One or More Drug Related Adverse Events	13 Participants

Secondary

Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)

ORR was defined as the percentage of randomized participants with a best overall response of complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Participants with unevaluable or unknown response status are considered nonresponders. Complete response (CR) is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions. Progressive disease (PD) is defined as at least a 20% increase in the sum LD of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) and the 20% increase must be at least one lesion must increase by an absolute value of ≥5 mm to be considered progression.

Time frame: Baseline to Measured Progressive Disease (Up to 13 Months )

Population: All randomized participants who received at least one dose of study drug and had PR/CR data.

Arm	Measure	Value (NUMBER)
Abemaciclib 150 mg	Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)	8.3 percentage of participants
Abemaciclib 200 mg	Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)	7.7 percentage of participants

Secondary

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib and Its Metabolites Single Dose

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib and its Metabolites following a single oral dose.

Time frame: Cycle 1, Day(D)1; Predose, 1, 4, 6, 8, 10, 24, 48 Hours Postdose