Brain Metastases, Breast Cancer, Melanoma, Non-small Cell Lung Cancer
Conditions
Brief summary
The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive breast cancer, non-small cell lung cancer (NSCLC), or melanoma that has spread to the brain.
Interventions
DRUGAbemaciclib
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have brain metastases secondary to hormone receptor positive breast cancer, NSCLC, or melanoma. * Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A) or negative HER2- (Study Part B) breast cancer. * Participants in Study Part C must have HR+ breast cancer, NSCLC, or melanoma with brain lesions clinically indicated for surgical resection as well as consent to provide tissue for drug concentration determination after 5 to 14 days of study drug dosing. * Participants in Part D must have NSCLC of any subtype. * Participants in Part E must have melanoma of any subtype. * Participants in Part F must have HR+ breast cancer, NSCLC, or melanoma with leptomeningeal metastases. * For Parts A, B, D, and E: Must have at least 1 measurable brain lesion ≥10 millimeters (mm) in the longest diameter (LD). * For Part C (surgical): Have metastatic brain lesion(s) for which surgical resection is clinically indicated. * Have completed local therapy (surgical resection, whole-breast radiotherapy (WBRT), or SRS) ≥14 days prior to initiating abemaciclib and recovered from all acute effects. * If receiving concomitant corticosteroids, must be on a stable or decreasing dose for at least 7 days prior to the baseline Gd-MRI. * Have a Karnofsky performance status of ≥70. * Have a life expectancy ≥12 weeks. * For HR+ breast cancer participants in part A, B, C, and F: If currently receiving endocrine therapy, a participant may continue to receive the same endocrine therapy provided that extracranial disease is stable for at least 3 months and central nervous system (CNS) disease progression has occurred while on this endocrine therapy. If these conditions are not met, participants must discontinue endocrine therapy prior to initiation of abemaciclib. * For HER2+ breast cancer participants in parts A, C, and F: participants may receive concurrent treatment (ongoing or initiated simultaneously with abemaciclib) with IV trastuzumab. * For NSCLC participants in parts C, D, and F: if currently receiving gemcitabine or pemetrexed (single-agent or in combination with another therapy), a participant may continue to receive 1 of these 2 therapies provided that extracranial disease is stable for at least 6 weeks and CNS disease progression has occurred while on this therapy. * Have adequate organ function.
Exclusion criteria
* Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases. * Are taking concurrent enzyme-inducing antiepileptic drugs (EIAED). * Have evidence of significant (ie, symptomatic) intracranial hemorrhage. * For Parts A, B, C, D, E: Have evidence of leptomeningeal metastases. Note: discrete dural metastases are permitted. * Have experienced \>2 seizures within 4 weeks prior to study entry. * For Parts A, B, D, E, and F: Have previously received treatment with any cyclin dependent kinase 6 (CDK6) inhibitor. For Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment. * Have known contraindication to Gd-MRI. * Have a preexisting chronic condition resulting in persistent diarrhea.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR) | Baseline to Objective Disease Progression (Up to 36 Months) | OIRR is the percentage of participants with a (CR) or (PR) based on the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM) response criteria. CR is measurable target lesions, the disappearance of all central nervous system (CNS) target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum longest duration (LD) of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Nontarget lesions requires disappearance CNS non-target lesions and no new CNS lesions. Stable disease (SD) is less than (\<)30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. Progressive disease (PD) is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 millimeter (mm). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Up to 36 Months) | Percentage of Participants with BOIR was categorized as CR, PR, SD, PD or NE, as defined by RANO-BM, from baseline until the earliest of objective progression according to brain metastases response criteria or start of new anticancer therapy. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. SD is \<30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. NE is absent (no abnormality; normal), or non-evaluable (NE). |
| Duration of CR or PR: Duration of Intracranial Response (DOIR) | Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up to 36 Months) | DOIR is measured from the date of first evidence of a confirmed response (CR or PR), as defined by RANO-BM, to the date objective progression or death from any cause. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Participants who have neither progressed nor died were censored on the day of their last radiographic tumor assessment or on the date of response. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. DOIR was summarized using Kaplan-Meier estimates. |
| Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR) | Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months) | Percentage of participants with BOIR of CR, PR, or SD: IDCR, as defined by RANO-BM is reported. CR is measurable target lesions, the disappearance of all central nervous system CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Nontarget lesions requires disappearance CNS non-target lesions and no new CNS lesions. SD is less than (\<)30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. |
| Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR) | Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months) | ICBR is the percentage of participants with BOIR of CR, PR, or SD with duration of SD for at least 6 months, as defined by RANO-BM. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. SD is \<30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. |
| Progression Free Survival (PFS) Bi-compartmental | Baseline to Objective Disease Progression or Death from Any Cause (Up to 36 Months) | PFS was measured from baseline to objective progression (intracranial or extracranial) as defined by (RANO-BM.) or death from any cause. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. PFS was summarized using Kaplan-Meier estimates. |
| Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR) | Baseline to Disease Progression (Up to 36 Months) | The percentage of participants with a best response of CR or PR objective response rate is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. PD is defined as at least a 20% increase in the sum LD of CNS 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. |
| Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR) | Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months) | Disease control rate (DCR) (CR+ PR+ SD) per RECIST v1.1. is defined as the percentage of participants with best overall response of CR, PR, or SD. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. PD is defined as at least a 20% increase in the sum LD of CNS 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. |
| Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | Baseline, Cycle 3 (Up to 63 Days) | The MDASI-BT is an instrument to assess multi-symptoms in participants with brain tumor metastases (including those with brain metastases secondary to breast cancer). The MDASI-BT of participants with a change from baseline is reported as mean core symptoms, mean brain tumor symptoms, and symptom groupings (mean focal neurologic deficit, mean generalized/disease status symptoms, and mean gastrointestinal symptoms). The mean of all symptom subscale items was calculated where 0 equals not present and 10 equals as bad as you can imagine. A change from baseline with negative values indicate improvement, positive values indicate worsening. |
| Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | Parts A, B, D, E, F, Cycle 3, Day 1: Predose; Part C, Cycle 4, Day 1: Predose | A PK plasma sample was taken prior to abemaciclib dose to analyze the minimum concentrations of abemaciclib and its metabolites (Cmin) - Individual Cmin values were averaged if there were 3 or more available data points, otherwise individual data are reported. |
| Overall Survival (OS) | Baseline to the Date of Death from Any Cause (Up to 5 Years) | OS was measured from baseline to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for a particular analysis, OS was censored for that analysis at the date of last contact prior to the data inclusion cutoff date (contacts considered in the determination of last contact date include adverse event (AE) date, tumor assessment date, visit date, and last known alive date). OS was summarized using Kaplan-Meier estimates. |
Countries
Australia, Austria, Belgium, Canada, France, Israel, Italy, Spain, United States
Participant flow
Pre-assignment details
Completers include participants who died or discontinued study treatment due to progressive disease and is in follow up.
Participants by arm
| Arm | Count |
|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants with hormone receptor positive HR+, HER2+ breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 27 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET).
Participants may continue to receive treatment until discontinuation criteria are met. | 58 |
| Part C Abemaciclib: Surgical Resection Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 9 |
| Part D Abemaciclib: NSCLC Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 28 |
| Part E Abemaciclib: Melanoma Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 23 |
| Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | 17 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 7 | 0 | 0 | 1 | 2 |
| Overall Study | Sponsor Decision | 0 | 8 | 0 | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 5 | 3 | 2 | 1 | 2 |
Baseline characteristics
| Characteristic | Part B Abemaciclib: HR+, HER2- Breast Cancer | Part C Abemaciclib: Surgical Resection | Part A Abemaciclib: HR+, HER2+ Breast Cancer | Part D Abemaciclib: NSCLC | Part E Abemaciclib: Melanoma | Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.1 years STANDARD_DEVIATION 10.5 | 57.0 years STANDARD_DEVIATION 17.9 | 49.9 years STANDARD_DEVIATION 10.9 | 58.4 years STANDARD_DEVIATION 10.9 | 55.1 years STANDARD_DEVIATION 14.4 | 50.1 years STANDARD_DEVIATION 12.3 | 54.0 years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 8 Participants | 21 Participants | 20 Participants | 20 Participants | 14 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 1 Participants | 6 Participants | 8 Participants | 2 Participants | 2 Participants | 32 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants | 1 Participants | 7 Participants | 7 Participants | 1 Participants | 2 Participants | 33 Participants |
| Race (NIH/OMB) White | 35 Participants | 7 Participants | 17 Participants | 20 Participants | 22 Participants | 14 Participants | 115 Participants |
| Region of Enrollment Australia | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 9 Participants |
| Region of Enrollment Austria | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment Belgium | 8 Participants | 0 Participants | 4 Participants | 3 Participants | 3 Participants | 0 Participants | 18 Participants |
| Region of Enrollment Canada | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Region of Enrollment France | 14 Participants | 1 Participants | 7 Participants | 7 Participants | 1 Participants | 2 Participants | 32 Participants |
| Region of Enrollment Israel | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants |
| Region of Enrollment Italy | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 9 Participants | 0 Participants | 15 Participants |
| Region of Enrollment Spain | 2 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 7 Participants |
| Region of Enrollment United States | 24 Participants | 7 Participants | 11 Participants | 12 Participants | 7 Participants | 10 Participants | 71 Participants |
| Sex: Female, Male Female | 57 Participants | 8 Participants | 27 Participants | 14 Participants | 11 Participants | 14 Participants | 131 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants | 14 Participants | 12 Participants | 3 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 23 / 27 | 38 / 58 | 6 / 9 | 24 / 28 | 19 / 23 | 12 / 17 |
| other Total, other adverse events | 23 / 27 | 55 / 58 | 8 / 9 | 27 / 28 | 16 / 23 | 16 / 17 |
| serious Total, serious adverse events | 6 / 27 | 16 / 58 | 3 / 9 | 8 / 28 | 4 / 23 | 7 / 17 |
Outcome results
Primary
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)
OIRR is the percentage of participants with a (CR) or (PR) based on the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM) response criteria. CR is measurable target lesions, the disappearance of all central nervous system (CNS) target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum longest duration (LD) of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Nontarget lesions requires disappearance CNS non-target lesions and no new CNS lesions. Stable disease (SD) is less than (\<)30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. Progressive disease (PD) is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 millimeter (mm).
Time frame: Baseline to Objective Disease Progression (Up to 36 Months)
Population: All participants who had evaluable OIRR data with at least one measurable brain lesion at baseline (per RANO-BM) and for whom at least one post-baseline overall response assessment for intracranial disease is available. Parts C and F were exploratory per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR) | 0 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR) | 5.8 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR) | 0 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR) | 0 percentage of participants |
Secondary
Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale
The MDASI-BT is an instrument to assess multi-symptoms in participants with brain tumor metastases (including those with brain metastases secondary to breast cancer). The MDASI-BT of participants with a change from baseline is reported as mean core symptoms, mean brain tumor symptoms, and symptom groupings (mean focal neurologic deficit, mean generalized/disease status symptoms, and mean gastrointestinal symptoms). The mean of all symptom subscale items was calculated where 0 equals not present and 10 equals as bad as you can imagine. A change from baseline with negative values indicate improvement, positive values indicate worsening.
Time frame: Baseline, Cycle 3 (Up to 63 Days)
Population: All participants who received at least one dose of study drug and had at least 1 baseline and an evaluable post baseline assessment. Parts C and F were exploratory per protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean generalized disease status | -0.47 units on a scale | Standard Deviation 1.03 |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean brain tumor symptom severity | -0.47 units on a scale | Standard Deviation 0.57 |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean gastrointestinal symptom | -1.35 units on a scale | Standard Deviation 2.11 |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean focal neurologic deficit symptom severity | -0.84 units on a scale | Standard Deviation 0.92 |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean core symptom severity | -0.98 units on a scale | Standard Deviation 0.86 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean focal neurologic deficit symptom severity | -0.36 units on a scale | Standard Deviation 1.23 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean generalized disease status | 0 units on a scale | Standard Deviation 1.39 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean gastrointestinal symptom | 0.40 units on a scale | Standard Deviation 1.91 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean brain tumor symptom severity | -0.29 units on a scale | Standard Deviation 1.05 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean core symptom severity | -0.17 units on a scale | Standard Deviation 0.99 |
| Part D Abemaciclib: NSCLC | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean focal neurologic deficit symptom severity | -0.44 units on a scale | Standard Deviation 0.58 |
| Part D Abemaciclib: NSCLC | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean core symptom severity | -0.38 units on a scale | Standard Deviation 1.19 |
| Part D Abemaciclib: NSCLC | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean brain tumor symptom severity | -0.10 units on a scale | Standard Deviation 1.22 |
| Part D Abemaciclib: NSCLC | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean generalized disease status | 0.28 units on a scale | Standard Deviation 1.51 |
| Part D Abemaciclib: NSCLC | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean gastrointestinal symptom | 1.00 units on a scale | Standard Deviation 1.46 |
| Part E Abemaciclib: Melanoma | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean generalized disease status | 0.01 units on a scale | Standard Deviation 0.89 |
| Part E Abemaciclib: Melanoma | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean brain tumor symptom severity | 0.31 units on a scale | Standard Deviation 1.11 |
| Part E Abemaciclib: Melanoma | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean core symptom severity | -0.53 units on a scale | Standard Deviation 0.62 |
| Part E Abemaciclib: Melanoma | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean focal neurologic deficit symptom severity | 0.54 units on a scale | Standard Deviation 1.16 |
| Part E Abemaciclib: Melanoma | Change From Baseline in Neurologic Symptoms on the MD Anderson Inventory-Brain Tumor (MDASI-BT) Subscale | mean gastrointestinal symptom | 0 units on a scale | Standard Deviation 0.29 |
Secondary
Duration of CR or PR: Duration of Intracranial Response (DOIR)
DOIR is measured from the date of first evidence of a confirmed response (CR or PR), as defined by RANO-BM, to the date objective progression or death from any cause. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Participants who have neither progressed nor died were censored on the day of their last radiographic tumor assessment or on the date of response. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. DOIR was summarized using Kaplan-Meier estimates.
Time frame: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up to 36 Months)
Population: All participants who had a confirmed intracranial response of CR or PR (per RANO-BM) and for whom at least one post-baseline overall intracranial response with a measurable duration is available. Parts C and F were exploratory per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Duration of CR or PR: Duration of Intracranial Response (DOIR) | 8.8 Months |
Secondary
Overall Survival (OS)
OS was measured from baseline to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for a particular analysis, OS was censored for that analysis at the date of last contact prior to the data inclusion cutoff date (contacts considered in the determination of last contact date include adverse event (AE) date, tumor assessment date, visit date, and last known alive date). OS was summarized using Kaplan-Meier estimates.
Time frame: Baseline to the Date of Death from Any Cause (Up to 5 Years)
Population: All participants who received at least one dose of study drug. Parts C and F were exploratory per protocol. Censored participants in Part A = 4, Part B = 20, Part D = 4, Part E = 4.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Overall Survival (OS) | 10.06 months |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Overall Survival (OS) | 13.38 months |
| Part D Abemaciclib: NSCLC | Overall Survival (OS) | 7.13 months |
| Part E Abemaciclib: Melanoma | Overall Survival (OS) | 2.93 months |
Secondary
Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR)
Disease control rate (DCR) (CR+ PR+ SD) per RECIST v1.1. is defined as the percentage of participants with best overall response of CR, PR, or SD. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. PD is defined as at least a 20% increase in the sum LD of CNS 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 Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Population: All participants who received at least one dose of study drug. Parts C and F were exploratory per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR) | 40.7 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR) | 51.7 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR) | 39.3 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants With a Best Overall Response of CR, PR, or SD: Extracranial Disease Control Rate (EDCR) | 26.1 percentage of participants |
Secondary
Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR)
The percentage of participants with a best response of CR or PR objective response rate is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. PD is defined as at least a 20% increase in the sum LD of CNS 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 Disease Progression (Up to 36 Months)
Population: All participants who received at least one dose of study drug. Parts C and F were exploratory per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR) | 0 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR) | 1.7 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR) | 3.6 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants With a Best Response of CR or PR: Extracranial Objective Response Rate (EORR) | 0 percentage of participants |
Secondary
Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR)
Percentage of participants with BOIR of CR, PR, or SD: IDCR, as defined by RANO-BM is reported. CR is measurable target lesions, the disappearance of all central nervous system CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Nontarget lesions requires disappearance CNS non-target lesions and no new CNS lesions. SD is less than (\<)30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm.
Time frame: Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Population: All participants who had evaluable OIRR data with at least one measurable brain lesion at baseline (per RANO-BM) and for whom at least one post-baseline overall response assessment. Parts C and F were exploratory per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR) | 52.2 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR) | 71.2 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR) | 43.5 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR) | 31.8 percentage of participants |
Secondary
Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR)
ICBR is the percentage of participants with BOIR of CR, PR, or SD with duration of SD for at least 6 months, as defined by RANO-BM. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. SD is \<30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm.
Time frame: Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)
Population: All participants who had evaluable OIRR data with at least one measurable brain lesion at baseline (per RANO-BM) and for whom at least one post-baseline overall response assessment for intracranial disease is available. Parts C and F were exploratory per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR) | 13.0 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR) | 26.9 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR) | 26.1 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR) | 9.1 percentage of participants |
Secondary
Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR)
Percentage of Participants with BOIR was categorized as CR, PR, SD, PD or NE, as defined by RANO-BM, from baseline until the earliest of objective progression according to brain metastases response criteria or start of new anticancer therapy. CR is measurable target lesions, the disappearance of all CNS target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum LD of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. SD is \<30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. NE is absent (no abnormality; normal), or non-evaluable (NE).
Time frame: Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Up to 36 Months)
Population: All participants who had evaluable OIRR data with at least one measurable brain lesion at baseline (per RANO-BM) and for whom at least one post-baseline overall response assessment for intracranial disease is available. Parts C and F were exploratory per protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Partial Response | 0 percentage of participants |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Stable Disease | 52.2 percentage of participants |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Progressive Disease | 47.8 percentage of participants |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Not Evaluable | 0 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Stable Disease | 65.4 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Progressive Disease | 28.8 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Not Evaluable | 0 percentage of participants |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Partial Response | 5.8 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Progressive Disease | 56.5 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Stable Disease | 43.5 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Not Evaluable | 0 percentage of participants |
| Part D Abemaciclib: NSCLC | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Partial Response | 0 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Not Evaluable | 0 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Stable Disease | 31.8 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Partial Response | 0 percentage of participants |
| Part E Abemaciclib: Melanoma | Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR) | Progressive Disease | 68.2 percentage of participants |
Secondary
Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18)
A PK plasma sample was taken prior to abemaciclib dose to analyze the minimum concentrations of abemaciclib and its metabolites (Cmin) - Individual Cmin values were averaged if there were 3 or more available data points, otherwise individual data are reported.
Time frame: Parts A, B, D, E, F, Cycle 3, Day 1: Predose; Part C, Cycle 4, Day 1: Predose
Population: All participants who had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | Abemaciclib | 133 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 13.4 |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN2839567 (M2) | 72.6 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 8.23 |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106726 (M20) | 158 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106729 (M18) | 36.8 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 39.3 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106726 (M20) | 133 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 160 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN2839567 (M2) | 77.3 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 121 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | Abemaciclib | 120 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 186 |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106729 (M18) | 42.4 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 85.6 |
| Part D Abemaciclib: NSCLC | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106729 (M18) | NA nanogram/milliliter (ng/mL) | — |
| Part D Abemaciclib: NSCLC | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106726 (M20) | NA nanogram/milliliter (ng/mL) | — |
| Part D Abemaciclib: NSCLC | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN2839567 (M2) | NA nanogram/milliliter (ng/mL) | — |
| Part D Abemaciclib: NSCLC | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | Abemaciclib | NA nanogram/milliliter (ng/mL) | — |
| Part E Abemaciclib: Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | Abemaciclib | 306 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 33.5 |
| Part E Abemaciclib: Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106729 (M18) | 28.9 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 108 |
| Part E Abemaciclib: Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN2839567 (M2) | 100 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 77.5 |
| Part E Abemaciclib: Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106726 (M20) | 203 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 43.3 |
| Part E 200 mg Abemaciclib: Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106726 (M20) | NA nanogram/milliliter (ng/mL) | — |
| Part E 200 mg Abemaciclib: Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106729 (M18) | NA nanogram/milliliter (ng/mL) | — |
| Part E 200 mg Abemaciclib: Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN2839567 (M2) | NA nanogram/milliliter (ng/mL) | — |
| Part E 200 mg Abemaciclib: Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | Abemaciclib | NA nanogram/milliliter (ng/mL) | — |
| Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN2839567 (M2) | 68.5 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 150 |
| Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106726 (M20) | 122 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 137 |
| Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | LSN3106729 (M18) | 27.0 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 242 |
| Part F 200 mg Abemaciclib: HR+ Breast Cancer, NSCLC, Melanoma | Pharmacokinetics (PK): Steady State Minimum Concentration (Cmin) of Abemaciclib and Its Metabolites LSN2839567 (M2), LSN3106726 (M20), and LSN3106729 (M18) | Abemaciclib | 142 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 80 |
Secondary
Progression Free Survival (PFS) Bi-compartmental
PFS was measured from baseline to objective progression (intracranial or extracranial) as defined by (RANO-BM.) or death from any cause. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment. PD is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 mm. PFS was summarized using Kaplan-Meier estimates.
Time frame: Baseline to Objective Disease Progression or Death from Any Cause (Up to 36 Months)
Population: All participants who received at least one dose of study drug. Censored participants Part A = 1, Part B =2, Part D = 1 and Part E = 1. Parts C and F were exploratory per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A Abemaciclib: HR+, HER2+ Breast Cancer | Progression Free Survival (PFS) Bi-compartmental | 2.07 Months |
| Part B Abemaciclib: HR+, HER2- Breast Cancer | Progression Free Survival (PFS) Bi-compartmental | 4.41 Months |
| Part D Abemaciclib: NSCLC | Progression Free Survival (PFS) Bi-compartmental | 1.45 Months |
| Part E Abemaciclib: Melanoma | Progression Free Survival (PFS) Bi-compartmental | 1.22 Months |