Neoplasm Metastasis, Lymphoma
Conditions
Brief summary
The main purpose of this study is to evaluate safety and side effects of LY2835219 in Japanese participants with advanced cancer.
Interventions
DRUGLY2835219
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have histological or cytological evidence of a diagnosis of cancer (either a solid tumor or a lymphoma) that is advanced and/or metastatic * Must be, in the judgment of the investigator, an appropriate candidate for the experimental therapy after available standard therapies have failed to provide clinical benefit for their disease * Have the presence of measurable or non-measurable disease as defined by the Response Evaluation Criteria in Solid Tumors Guideline Version 1.1, or the Revised Response Criteria for Malignant Lymphoma Guideline * Have adequate organ function * Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, and investigational therapy, for at least 21 days before the first dose of study drug and recovered from the acute effects of any such therapy * Males must agree to use medically approved barrier contraceptive precautions during the study and for 3 months following the last dose of study drug * Females with child bearing potential: must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug, must have had a negative serum or urine pregnancy test ≤7 days before the first dose of study drug. * A breastfeeding woman must not be breastfeeding. If a female who stops breastfeeding enters the study, the female must stop breastfeeding from the day of the first study drug administration until at least 3 months after the last administration * Have an estimated life expectancy of ≥12 weeks * Are able to swallow capsules
Exclusion criteria
* Have received treatment within 21 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication * Have a medical history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (e.g., ventricular tachycardia and ventricular fibrillation) or sudden cardiac arrest * Have a baseline with any of the following findings on screening electrocardiogram (ECG): ventricular tachycardia, ventricular fibrillation, abnormal QTc using Bazett's formula (QTcB) (defined as ≥470 milliseconds), or evidence of acute myocardial ischemia * Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel) * Have symptomatic central nervous system (CNS) malignancy or metastasis. For asymptomatic participants without history of CNS malignancy or metastases * Have evidence or history of a leukemia * Have received a stem-cell transplant. As an exception, a participant with lymphoma who received an autologous stem-cell transplant is eligible for the study, if more than 75 days have passed before the initial dose of study drug * Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus \[HIV\], hepatitis B, or hepatitis C)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Abemaciclib Dose-Limiting Toxicity (DLT) | Cycle 1 = 32 days | DLT is defined as an adverse event between Day -3 and Day 29 of Cycle 1 that is possibly related to the study drug and fulfills any one of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib | Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hours (hr) postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days) | Maximum plasma concentration on Day -3 and Day 28 of Cycle 1. |
| Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib | Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hr postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days) | AUC on Day -3 and Day 28 of Cycle 1 are AUC from time zero to infinity \[AUC(0-∞)\] and AUC during one dosing interval at steady state (AUCτ,ss), respectively. |
| Percentage of Participants With a Tumor Response: Objective Response Rate (ORR) | Baseline to Measured Progressive Disease (Up To 24 months) | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions. |
Countries
Japan
Participant flow
Recruitment details
Participants completed the trial if they received at least one dose of study drug and met discontinuation criteria.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - 100 mg Abemaciclib 100 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met. | 3 |
| Cohort 2 - 150 mg Abemaciclib 150 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met. | 3 |
| Cohort 3 - 200 mg Abemaciclib 200 mg abemaciclib administered orally Q12H in 28 day cycles. (Cycle 1 = 32 days.) Participants remained on treatment until discontinuation criteria were met. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Cohort 1 - 100 mg Abemaciclib | Total | Cohort 3 - 200 mg Abemaciclib | Cohort 2 - 150 mg Abemaciclib |
|---|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 11.06 | 59.1 years STANDARD_DEVIATION 9.77 | 56.0 years STANDARD_DEVIATION 11.7 | 63.0 years STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 12 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 3 Participants | 12 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 0 / 3 | 2 / 3 | 2 / 6 |
Outcome results
Primary
Number of Participants With Abemaciclib Dose-Limiting Toxicity (DLT)
DLT is defined as an adverse event between Day -3 and Day 29 of Cycle 1 that is possibly related to the study drug and fulfills any one of the following criteria using the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
Time frame: Cycle 1 = 32 days
Population: All participants who received at least one dose of study drug and took at least 75% of planned dose in Cycle 1 or experienced a DLT in Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 - 100 mg Abemaciclib | Number of Participants With Abemaciclib Dose-Limiting Toxicity (DLT) | 0 Participants |
| Cohort 2 - 150 mg Abemaciclib | Number of Participants With Abemaciclib Dose-Limiting Toxicity (DLT) | 0 Participants |
| Cohort 3 - 200 mg Abemaciclib | Number of Participants With Abemaciclib Dose-Limiting Toxicity (DLT) | 1 Participants |
Secondary
Percentage of Participants With a Tumor Response: Objective Response Rate (ORR)
Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions.
Time frame: Baseline to Measured Progressive Disease (Up To 24 months)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 - 100 mg Abemaciclib | Percentage of Participants With a Tumor Response: Objective Response Rate (ORR) | 0 percentage of participants |
| Cohort 2 - 150 mg Abemaciclib | Percentage of Participants With a Tumor Response: Objective Response Rate (ORR) | 0 percentage of participants |
| Cohort 3 - 200 mg Abemaciclib | Percentage of Participants With a Tumor Response: Objective Response Rate (ORR) | 0 percentage of participants |
Secondary
Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib
AUC on Day -3 and Day 28 of Cycle 1 are AUC from time zero to infinity \[AUC(0-∞)\] and AUC during one dosing interval at steady state (AUCτ,ss), respectively.
Time frame: Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hr postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days)
Population: All participants who received at least one dose of study drug and had evaluable data for AUC.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - 100 mg Abemaciclib | Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib | AUC(0-∞) | NA Nanogram*hour/Millilitre (ng*hr/mL) | — |
| Cohort 1 - 100 mg Abemaciclib | Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib | AUCτ,ss (n=2,2,5) | NA Nanogram*hour/Millilitre (ng*hr/mL) | — |
| Cohort 2 - 150 mg Abemaciclib | Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib | AUC(0-∞) | 4450 Nanogram*hour/Millilitre (ng*hr/mL) | Geometric Coefficient of Variation 39 |
| Cohort 2 - 150 mg Abemaciclib | Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib | AUCτ,ss (n=2,2,5) | NA Nanogram*hour/Millilitre (ng*hr/mL) | — |
| Cohort 3 - 200 mg Abemaciclib | Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib | AUC(0-∞) | 5480 Nanogram*hour/Millilitre (ng*hr/mL) | Geometric Coefficient of Variation 95 |
| Cohort 3 - 200 mg Abemaciclib | Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve (AUC) of Abemaciclib | AUCτ,ss (n=2,2,5) | 3020 Nanogram*hour/Millilitre (ng*hr/mL) | Geometric Coefficient of Variation 73 |
Secondary
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib
Maximum plasma concentration on Day -3 and Day 28 of Cycle 1.
Time frame: Cycle 1 Day -3: Predose, 1, 2, 4, 6, 8, 10, 24, 48 and 72 hours (hr) postdose; Cycle 1 Day 28: Predose, 1, 2, 4, 6, 8, 10 and 24 hr postdose (Cycle 1 = 32 days)
Population: All participants who received at least one dose of study drug and had evaluable data for Cmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 - 100 mg Abemaciclib | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib | Cycle 1 Day -3 | 127 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| Cohort 1 - 100 mg Abemaciclib | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib | Cycle 1 Day 28 | NA nanogram per milliliter (ng/mL) | — |
| Cohort 2 - 150 mg Abemaciclib | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib | Cycle 1 Day -3 | 167 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| Cohort 2 - 150 mg Abemaciclib | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib | Cycle 1 Day 28 | NA nanogram per milliliter (ng/mL) | — |
| Cohort 3 - 200 mg Abemaciclib | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib | Cycle 1 Day -3 | 214 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 87 |
| Cohort 3 - 200 mg Abemaciclib | Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of Abemaciclib | Cycle 1 Day 28 | 298 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 64 |