Advanced Cancer
Conditions
Brief summary
The purpose of this study is to determine a safe dose of Abemaciclib to be given to participants with advanced cancer and to determine any side effects that may be associated with Abemaciclib in this population. Efficacy measures will be used to assess the activity of Abemaciclib in this population.
Interventions
DRUGAbemaciclib
Administered orally.
DRUGFulvestrant
Fulvestrant is administered intramuscularly into the buttocks in Part G only.
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For all Parts (Dose escalation and expansion): The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy either after available standard therapies have ceased to provide clinical benefit (Parts A, B, C, D, E and F) or in combination with fulvestrant (Part G only) * For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced and/or metastatic * For Dose Expansion (Parts B, C, D, E, F and G): The participant must have histological or cytological evidence of one of the following cancers: * Part B: Non-small cell lung cancer of any subtype that is advanced and/or metastatic * Part C: Glioblastoma multiforme that has progressed or recurred after radiotherapy and/or chemotherapy * Part D: Breast cancer that is advanced and/or metastatic * Part E: Melanoma that is advanced and/or metastatic * Part F: Colorectal Cancer * Part G: Breast Cancer that is not only advanced and/or metastatic but also hormone receptor positive * As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma * For Parts A and G: Have measurable or nonmeasurable disease * For Parts B, C, D, E and F: Have measurable disease * Have given written informed consent prior to any study-specific procedures * Have adequate hematologic, hepatic, and renal function * Have a performance status less than or equal to 1 for Dose Escalation (Part A) and less than or equal to 2 for Dose Confirmation (Parts B, C, D, E, F and G) on the Eastern Cooperative Oncology Group (ECOG) scale * Have discontinued all previous therapies for cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy) with the exception of fulvestrant (for Part G only) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (treatment related toxicity resolved to baseline) except for residual alopecia * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug * Females with child bearing potential must have a negative serum pregnancy test within 3 days of the first dose of study drug * Have an estimated life expectancy of greater than or equal to 12 weeks * Are able to swallow capsules
Exclusion criteria
* Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively * Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), sudden cardiac death or sudden cardiac arrest * 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) * For Dose Escalation (Part A): Have central nervous system (CNS) malignancy or metastasis * For Dose Confirmation (Parts B, D, E, F and G): Have CNS metastasis that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids * For Dose Confirmation (Part C): Have glioblastoma multiforme that is radiographically or clinically unstable less than 14 days prior to receiving study drug, regardless of whether they are receiving corticosteroids * Have an acute leukemia * Have received an autologous or allogeneic stem-cell transplant within 75 days of the initial dose of study drug * Females who are pregnant or lactating * Have active bacterial, fungal, and/or known viral infection (for example, human immunodeficiency virus \[HIV\] antibodies, hepatitis B surface antigen \[HBSAg\], or hepatitis C antibodies) Screening is not required for enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Effects | Baseline up to 233 weeks | The number of participants with clinically significant findings in the study were reported in this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | Baseline through Study Completion (Up to 285 weeks) | ORR is the percentage of participants who exhibit a confirmed complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. DCR is defined as the percentage of participants in the analysis population who exhibit a stable disease (SD) or confirmed CR or PR relative to baseline during the study. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. |
| Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | Day 28 (0, 1, 2, 4, 6, 8, 10, 24 hours post-dose) of Cycle 1 | PK: Cmax,ss of Abemaciclib. |
| PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | Day 28 (0, 1, 2, 4, 6, 8, 10, 24 hours post-dose) of Cycle 1 | PK: AUC 0-24hr,ss of Abemaciclib. |
| Part A: Recommended Dose for Phase 2 Studies | Baseline through Study Completion (Up to 285 weeks) | The recommended dose was determined based on a review of overall toxicity, dose reductions, omissions, and pharmacokinetic information from the study. |
Countries
United States
Participant flow
Recruitment details
This study has Dose Escalation (Part A) and Dose Confirmation (Parts B, C, D, E, F, and G) phases. Participants included -Part A: participants with histological and cytological evidence of cancer; Part B: Non-small cell lung cancer; Part C: Glioblastoma multiforme; Part D: Advanced and/or metastatic breast cancer; Part E: Advanced and/or metastatic melanoma; Part F: Advanced and/or metastatic colorectal cancer. Part G: Advanced and/or metastatic breast cancer but also hormone receptor positive.
Pre-assignment details
Completed is defined as for participants from Study Part-A: those who all completed one cycle of treatment or discontinued due to an adverse event and completed study follow up procedures, and for remaining all cohorts (B, C, D, E, F, G) who all were treated until disease progression (objective or symptomatic) or death or discontinued due to an adverse event and completed study follow-up procedures.
Participants by arm
| Arm | Count |
|---|---|
| Part A - Cohort 1: 50 mg Abemaciclib - Q24H Participants received 50 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 4 |
| Part A - Cohort 2: 100 mg Abemaciclib - Q24H Participants received 100 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 3 |
| Part A - Cohort 3: 150 mg Abemaciclib - Q24H Participants received 150 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 3 |
| Part A - Cohort 4: 225 mg Abemaciclib - Q24H Participants received 225 mg of oral Abemaciclib administered Q24H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3 and then on Days 1 to 27. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 3 |
| Part A - Cohort 5: 75 mg Abemaciclib - Q12H Participants received 75 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 3 |
| Part A - Cohort 6: 100 mg Abemaciclib - Q12H Participants received 100 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 4 |
| Part A - Cohort 7: 150 mg Abemaciclib - Q12H Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 3 |
| Part A - Cohort 8: 200 mg Abemaciclib- Q12H Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 7 |
| Part A - Cohort 9: 275 mg Abemaciclib - Q12H Participants received 275 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 3 |
| Part B - 150 mg Abemaciclib - Q12H Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 26 |
| Part B - 200 mg Abemaciclib - Q12H Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 42 |
| Part C - 150 mg Abemaciclib - Q12H Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 2 |
| Part C - 200 mg Abemaciclib - Q12H Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 15 |
| Part D - 150 mg Abemaciclib - Q12H Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 25 |
| Part D - 200 mg Abemaciclib - Q12H Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 22 |
| Part E - 150 mg Abemaciclib - Q12H Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 13 |
| Part E - 200 mg Abemaciclib - Q12H Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 13 |
| Part F - 150 mg Abemaciclib - Q12H Participants received 150 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 15 |
| Part G - 200 mg Abemaciclib (Q12H)+ Fulvestrant Participants received 200 mg of oral Abemaciclib administered Q12H on Days 1 through 28 of a 28-day cycle except in Cycle 1, where the study drug was administered as a single dose on Day -3, every 12 hours on Days 1 to 27, and as a single dose on Day 28. The study drug was given along with 500 mg of fulvestrant administered intramuscularly during the treatment period. The treatment was continued until a discontinuation criterion was met or under Sponsor's discretion. | 19 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Progressive Disease | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 4 | 0 | 0 | 3 | 1 | 3 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Part A - Cohort 2: 100 mg Abemaciclib - Q24H | Part A - Cohort 3: 150 mg Abemaciclib - Q24H | Part A - Cohort 4: 225 mg Abemaciclib - Q24H | Part A - Cohort 5: 75 mg Abemaciclib - Q12H | Part A - Cohort 6: 100 mg Abemaciclib - Q12H | Part A - Cohort 7: 150 mg Abemaciclib - Q12H | Part A - Cohort 8: 200 mg Abemaciclib- Q12H | Part A - Cohort 9: 275 mg Abemaciclib - Q12H | Part B - 150 mg Abemaciclib - Q12H | Part B - 200 mg Abemaciclib - Q12H | Part A - Cohort 1: 50 mg Abemaciclib - Q24H | Part C - 150 mg Abemaciclib - Q12H | Part C - 200 mg Abemaciclib - Q12H | Part D - 150 mg Abemaciclib - Q12H | Part D - 200 mg Abemaciclib - Q12H | Part E - 150 mg Abemaciclib - Q12H | Part E - 200 mg Abemaciclib - Q12H | Part F - 150 mg Abemaciclib - Q12H | Part G - 200 mg Abemaciclib (Q12H)+ Fulvestrant |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 89 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 15 Participants | 19 Participants | 0 Participants | 2 Participants | 2 Participants | 7 Participants | 3 Participants | 8 Participants | 8 Participants | 7 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 136 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants | 2 Participants | 5 Participants | 2 Participants | 11 Participants | 23 Participants | 4 Participants | 0 Participants | 13 Participants | 18 Participants | 19 Participants | 5 Participants | 5 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 4 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 197 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 7 Participants | 2 Participants | 24 Participants | 39 Participants | 4 Participants | 2 Participants | 15 Participants | 21 Participants | 18 Participants | 11 Participants | 12 Participants | 11 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 212 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 7 Participants | 2 Participants | 24 Participants | 39 Participants | 4 Participants | 2 Participants | 15 Participants | 24 Participants | 20 Participants | 13 Participants | 13 Participants | 12 Participants | 18 Participants |
| Region of Enrollment United States | 225 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 7 Participants | 3 Participants | 26 Participants | 42 Participants | 4 Participants | 2 Participants | 15 Participants | 25 Participants | 22 Participants | 13 Participants | 13 Participants | 15 Participants | 19 Participants |
| Sex: Female, Male Female | 150 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 6 Participants | 3 Participants | 15 Participants | 21 Participants | 1 Participants | 1 Participants | 9 Participants | 24 Participants | 22 Participants | 3 Participants | 5 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 75 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 11 Participants | 21 Participants | 3 Participants | 1 Participants | 6 Participants | 1 Participants | 0 Participants | 10 Participants | 8 Participants | 6 Participants | 0 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 7 | 1 / 3 | 3 / 26 | 15 / 42 | 0 / 2 | 7 / 15 | 4 / 25 | 0 / 22 | 1 / 13 | 5 / 13 | 0 / 15 | 2 / 19 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 7 / 7 | 3 / 3 | 26 / 26 | 42 / 42 | 2 / 2 | 15 / 15 | 25 / 25 | 22 / 22 | 13 / 13 | 13 / 13 | 15 / 15 | 19 / 19 |
| serious Total, serious adverse events | 0 / 4 | 1 / 3 | 1 / 3 | 0 / 3 | 1 / 3 | 1 / 4 | 1 / 3 | 1 / 7 | 1 / 3 | 7 / 26 | 15 / 42 | 1 / 2 | 3 / 15 | 5 / 25 | 7 / 22 | 5 / 13 | 5 / 13 | 3 / 15 | 4 / 19 |
Outcome results
Primary
Number of Participants With Clinically Significant Effects
The number of participants with clinically significant findings in the study were reported in this outcome measure.
Time frame: Baseline up to 233 weeks
Population: All participants who received at least one dose of the study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A - Cohort 1: 50 mg Abemaciclib - Q24H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part A - Cohort 2: 100 mg Abemaciclib - Q24H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part A - Cohort 3: 150 mg Abemaciclib - Q24H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part A - Cohort 4: 225 mg Abemaciclib - Q24H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part A - Cohort 5: 75 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part A - Cohort 6: 100 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part A - Cohort 7: 150 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part A - Cohort 8: 200 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 1 Participants |
| Part A - Cohort 9: 275 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 2 Participants |
| Part B - 150 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 1 Participants |
| Part B - 200 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 5 Participants |
| Part C - 150 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part C - 200 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 1 Participants |
| Part D - 150 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 2 Participants |
| Part D - 200 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 4 Participants |
| Part E - 150 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part E - 200 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 2 Participants |
| Part F - 150 mg Abemaciclib - Q12H | Number of Participants With Clinically Significant Effects | 0 Participants |
| Part G - 200 mg Abemaciclib (Q12H) + Fulvestrant | Number of Participants With Clinically Significant Effects | 6 Participants |
Secondary
Part A: Recommended Dose for Phase 2 Studies
The recommended dose was determined based on a review of overall toxicity, dose reductions, omissions, and pharmacokinetic information from the study.
Time frame: Baseline through Study Completion (Up to 285 weeks)
Population: All participants of Part A who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Cohort 1: 50 mg Abemaciclib - Q24H | Part A: Recommended Dose for Phase 2 Studies | 200 milligrams every 12 hours (mg Q12H) |
Secondary
Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR)
ORR is the percentage of participants who exhibit a confirmed complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. DCR is defined as the percentage of participants in the analysis population who exhibit a stable disease (SD) or confirmed CR or PR relative to baseline during the study. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions.
Time frame: Baseline through Study Completion (Up to 285 weeks)
Population: All participants in Parts B, C, D, E, F and G who received at least one dose of the study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A - Cohort 1: 50 mg Abemaciclib - Q24H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 3.8 Percentage of participants |
| Part A - Cohort 1: 50 mg Abemaciclib - Q24H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 42.3 Percentage of participants |
| Part A - Cohort 2: 100 mg Abemaciclib - Q24H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 2.4 Percentage of participants |
| Part A - Cohort 2: 100 mg Abemaciclib - Q24H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 52.4 Percentage of participants |
| Part A - Cohort 3: 150 mg Abemaciclib - Q24H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 0 Percentage of participants |
| Part A - Cohort 3: 150 mg Abemaciclib - Q24H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 0 Percentage of participants |
| Part A - Cohort 4: 225 mg Abemaciclib - Q24H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 0 Percentage of participants |
| Part A - Cohort 4: 225 mg Abemaciclib - Q24H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 20 Percentage of participants |
| Part A - Cohort 5: 75 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 32.0 Percentage of participants |
| Part A - Cohort 5: 75 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 68.0 Percentage of participants |
| Part A - Cohort 6: 100 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 72.7 Percentage of participants |
| Part A - Cohort 6: 100 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 18.2 Percentage of participants |
| Part A - Cohort 7: 150 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 23.1 Percentage of participants |
| Part A - Cohort 7: 150 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 0 Percentage of participants |
| Part A - Cohort 8: 200 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 7.7 Percentage of participants |
| Part A - Cohort 8: 200 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 30.8 Percentage of participants |
| Part A - Cohort 9: 275 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 0 Percentage of participants |
| Part A - Cohort 9: 275 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 13.3 Percentage of participants |
| Part B - 150 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 45.5 Percentage of participants |
| Part B - 150 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 72.7 Percentage of participants |
| Part B - 200 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | ORR | 0 Percentage of participants |
| Part B - 200 mg Abemaciclib - Q12H | Percentage of Participants With Tumor Response - Overall Response Rate (ORR), Disease Control Rate (DCR) | DCR | 87.5 Percentage of participants |
Secondary
Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib
PK: Cmax,ss of Abemaciclib.
Time frame: Day 28 (0, 1, 2, 4, 6, 8, 10, 24 hours post-dose) of Cycle 1
Population: PK analysis was conducted on participants who received the actual dose of Abemaciclib, irrespective of the treatment arm to which they were assigned, and had quantifiable data. So,4 participants from '200mg Abemaciclib' were reported under '100mg Abemaciclib' arm as they had their dose reduced to 100mg Abemaciclib. For 275mg Abemaciclib arm, 2 participants didn't have PK data collected on day 28, and dosing information was missing for remaining 1 participant. So, zero participants were analysed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A - Cohort 1: 50 mg Abemaciclib - Q24H | Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | NA nanograms per milliliter (ng/mL) | — |
| Part A - Cohort 2: 100 mg Abemaciclib - Q24H | Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | 102 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 198 |
| Part A - Cohort 3: 150 mg Abemaciclib - Q24H | Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | 189 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| Part A - Cohort 4: 225 mg Abemaciclib - Q24H | Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | 121 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| Part A - Cohort 5: 75 mg Abemaciclib - Q12H | Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | 58.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 37 |
| Part A - Cohort 6: 100 mg Abemaciclib - Q12H | Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | 226 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| Part A - Cohort 7: 150 mg Abemaciclib - Q12H | Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | 249 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 86 |
| Part A - Cohort 8: 200 mg Abemaciclib - Q12H | Pharmacokinetics (PK): Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Abemaciclib | 298 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 72 |
Secondary
PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib
PK: AUC 0-24hr,ss of Abemaciclib.
Time frame: Day 28 (0, 1, 2, 4, 6, 8, 10, 24 hours post-dose) of Cycle 1
Population: PK analysis was conducted on participants who received the actual dose of Abemaciclib, irrespective of the treatment arm to which they were assigned, and had quantifiable data. So,4 participants from '200mg Abemaciclib' were reported under '100mg Abemaciclib' arm as they had their dose reduced to 100mg Abemaciclib. For 275mg Abemaciclib arm, 2 participants didn't have PK data collected on day 28, and dosing information was missing for remaining 1 participant. So, zero participants were analysed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A - Cohort 1: 50 mg Abemaciclib - Q24H | PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | NA nanogram hour per milliliter (ng*h/mL) | — |
| Part A - Cohort 2: 100 mg Abemaciclib - Q24H | PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | 1840 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 172 |
| Part A - Cohort 3: 150 mg Abemaciclib - Q24H | PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | NA nanogram hour per milliliter (ng*h/mL) | — |
| Part A - Cohort 4: 225 mg Abemaciclib - Q24H | PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | NA nanogram hour per milliliter (ng*h/mL) | — |
| Part A - Cohort 5: 75 mg Abemaciclib - Q12H | PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | 1300 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 49 |
| Part A - Cohort 6: 100 mg Abemaciclib - Q12H | PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | 3910 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 53 |
| Part A - Cohort 7: 150 mg Abemaciclib - Q12H | PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | 4280 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 94 |
| Part A - Cohort 8: 200 mg Abemaciclib - Q12H | PK: Area Under the Steady State Plasma Concentration-time Curve Over 24 Hours (AUC 0-24hr,ss) of Abemaciclib | 5520 nanogram hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 70 |