Relapsed Solid Tumor, Refractory Solid Tumor
Conditions
Keywords
CDK4, CDK6, Ewing's sarcoma, Neuroblastoma, Recurrent neuroblastoma, Malignant rhabdoid tumor, Rhabdomyosarcoma, Osteosarcoma, Brain tumor, Glioblastoma, Malignant glioma, Diffuse intrinsic pontine glioma, Medulloblastoma, Ependymoma, Solid tumor, High-grade glioma
Brief summary
The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells. The study is open to children and young adults with solid tumors, including neuroblastoma, that did not respond or grew during other anti-cancer treatment. For each participant, the study is estimated to last up to 2 years.
Interventions
DRUGAbemaciclib
Administered orally
DRUGIrinotecan
Administered IV
DRUGTemozolomide
Administered orally
DRUGDinutuximab
Administered IV
DRUGGM-CSF
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
* Parts A and B only: * Participants must be less than or equal to (≤)18 years of age. * Body weight greater than or equal to (≥)10 kilograms and body surface area (BSA) ≥0.5 * Participants with any relapsed/refractory malignant solid tumor (excluding lymphoma), including central nervous system tumors, that have progressed on standard therapies. * For sites that are actively enrolling Parts B and C, participants with neuroblastoma who are eligible for Part C will be excluded from Part B unless approved by Lilly CRP/CRS. * Part C only: * Participants must be less than (\<) 21 years of age. * Participants have a BSA ≥0.2 m². * Participants with first relapse/refractory neuroblastoma. * All Parts * Participants must have measurable or evaluable disease by RECIST v1.1 or RANO. * A Lansky score ≥50 for participants \<16 years of age or Karnofsky score ≥50 for participants ≥16 years of age. * Participants must have discontinued all previous treatments for cancer or investigational agents and must have recovered from the acute effects to Grade ≤1 at the time of enrollment. * Able to swallow and/or have a gastric/nasogastric tube. * Adequate hematologic and organ function ≤2 weeks (14 days) prior to first dose of study drug. * Females of reproductive potential must have negative urine or serum pregnancy test at baseline (within 7 days prior to starting treatment). * Female participants of reproductive potential must agree to use highly effective contraceptive precautions during the trial. For abemaciclib, females should use contraception for at least 3 weeks following the last abemaciclib. For other study drugs, highly effective contraceptive precautions (and avoiding sperm donation) must be used according to their label. * Life expectancy of at least 8 weeks and able to complete at least 1 cycle of treatment. * Caregivers and participants willing to make themselves available for the duration of the trial.
Exclusion criteria
* Received allogenic bone marrow or solid organ transplant. * Received live vaccination. * Intolerability or hypersensitivity to any of the study treatments or its components. * Diagnosed and/or treated additional malignancy within 3 years prior to enrollment that may affect the interpretation of results, with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected in situ cervical and/or breast cancers. * Pregnant or breastfeeding. * Active systemic infections. * Serious and/or uncontrolled preexisting medical condition(s) that would preclude participation in this study. * Parts A and C only: Have a bowel obstruction. * Prior treatment with drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450 3A (CYP3A) or strong inhibitors of uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) if the treatment cannot be discontinued or switched to a different medication at least 5 half-lives prior to starting study drug. * Received prior treatment with cyclin-dependent kinase (CDK) 4 \& 6 inhibitor. * Part C only: Received prior systemic therapy for relapsed/refractory neuroblastoma. * Part C only, have received prior anti-GD2 therapy during induction phase. * Currently enrolled in any other clinical study involving an investigational product or non-approved use of a drug or device. * Has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Abemaciclib in Part A | Cycle 1 (21 Days) | The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT. |
| Recommended Phase 2 Dose (RP2D) of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A) | Cycles 1 and 2 (21 Day Cycles) | The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 50 mg/m²/day irinotecan and 100 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported. |
| Number or Participants With Dose Limiting Toxicities (DLTs) in Part A | Cycle 1 (21 Day Cycle) | DLT was 1 of the following adverse events likely related to abemaciclib/combination and fulfils any 1 of the following criteria graded per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0: * Any non-hematologic Grade (G) ≥3 toxicity, except: * G3 diarrhea lasting \<72 hour (h) * Acute irinotecan-associated diarrhea lasting \<7 days * G≥3 nausea, vomiting, constipation that lasts \<72 h * G3 mucositis/stomatitis lasting \<72 h * G3 fever/infection * G≥3 electrolyte abnormality that lasts \<72 h, is not complicated, and resolves spontaneously or responds to conventional medication; * G≥3 amylase/lipase that is not associated with symptoms/clinical manifestations of pancreatitis; or * AST/ALT elevation resolving to eligibility criteria within 7 days; * Hematologic toxicities considered a DLT: * A \>14-day Cycle 2 delay due to neutropenia/thrombocytopenia * G≥3 thrombocytopenia with significant bleeding; or * G≥ 4 neutropenic fever |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A | Pre-dose, 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle) | PK: (AUC0-tlast) was reported. |
| PK: (AUC0-tlast) of Irinotecan in Part A | 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle) | PK: AUC0-tlast) was reported. |
| PK: (AUC0-tlast) of Temozolomide in Part A | 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle) | PK: AUC0-tlast was reported. |
| RP2D of Abemaciclib in Combination With Temozolomide (Part B) | Cycles 1 and 2 (21 Day Cycles) | The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 150 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported. |
| Number or Participants With DLTs in Part B | Cycle 1 (21 Day Cycle) | A DLT was 1 of the following adverse events likely related to abemaciclib/combination and fulfils any 1 of the following criteria graded as per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0: * Any non-hematologic Grade (G) ≥3 toxicity, except: * G3 diarrhea lasting \<72 hr * Acute irinotecan-associated diarrhea lasting \<7 days * G≥3 nausea, vomiting, constipation that lasts \<72 hr * G3 mucositis/stomatitis lasting \<72 hr * G3 fever/infection * G≥3 electrolyte abnormality that lasts \<72 hr, is not complicated, and resolves spontaneously or responds to conventional medication; * G≥3 amylase/lipase that is not associated with symptoms/clinical manifestations of pancreatitis; or * AST/ALT elevation resolving to eligibility criteria within 7 days; * Hematologic toxicities considered a DLT: * A \>14-day Cycle 2 delay due to neutropenia/thrombocytopenia * G≥3 thrombocytopenia with significant bleeding; or * G≥ 4 neutropenic fever |
| MTD of Abemaciclib in Part B | Cycle 1 (21 Days) | The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT. |
| PK: AUC0-tlast of Abemaciclib in Part B | Pre-dose, 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle) | PK: AUC0-tlast was reported. |
| PK: AUC0-tlast of Temozolomide in Part B | 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle) | PK: AUC0-tlast was reported. |
| Number of Participants With Overall Response Rate (ORR) in Part C. | Date of first dose to disease progression or death (Up to 25 Months) | ORR: Number of participants with best response of Complete Response (CR), Partial Response (PR), or Minor Response (MR) per International Neuroblastoma Response Criteria (INRC). * CR is defined as complete response in all response components: * Primary Tumor: \<10 mm residual soft tissue primary site and complete resolution of MIBG-avid tumors * Soft tissue and bone metastatic response: nonprimary target and nontarget lesions \<10 mm and nodes identified as targets decreased to short axis \<10mm and MIBG-avid update of nonprimary lesions completely resolved * Bone marrow response: no tumor infiltration on reassessment; disappearance of all target lesions; * PR is defined as PR in \>1component and all other components are either CR, minimal disease (MD) (bone marrow only), PR (soft tissue or bone), or not involved (NI) and no components with progressive disease (PD). * MR is defined PR or CR in \>1 component and SD in \>1 component and no component with PD |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Response Rate (ORR): Part A | Date of first dose to disease progression or death (Up to 25 Months) | ORR: Percentage of participants with best response of CR or PR per Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO). RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). |
| Percentage of Participants With ORR: Part B | Date of first dose to disease progression or death (Up to 25 Months) | ORR: Percentage of participants with best response of CR or PR per Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO). RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). |
| Duration of Response (DoR): Parts A and B. | Date of first evidence of a CR or PR to date of objective disease progression or death due to any cause (Up to 25 Months) | DoR is the time between first evidence of CR or PR and disease progression or death due to any cause. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). |
| Duration of Response (DoR): Part C | Date of first evidence of a CR, PR, or MR to date of objective disease progression or death due to any cause (Up to 25 Months) | DoR is the time between first evidence of CR, PR or MR and disease progression or death due to any cause. CR, PR, and MR was as per International Neuroblastoma Response Criteria (INRC). \- CR is defined as complete response in all response components: Primary Tumor: \<10 mm residual soft tissue primary site and complete resolution of MIBG-avid tumors Soft tissue and bone metastatic response: nonprimary target and nontarget lesions \<10 mm and nodes identified as targets decreased to short axis \<10mm and MIBG-avid update of nonprimary lesions completely resolved Bone marrow response: no tumor infiltration on reassessment; disappearance of all target lesions; * PR is defined as PR in \>1 component and all other components are either CR, minimal disease (MD) (bone marrow only), PR (soft tissue or bone), or not involved (NI) and no components with progressive disease (PD). * MR is defined PR or CR in \>1 component and SD in \>1 component and no component with PD |
| Percentage of Participants With Clinical Benefit Rate (CBR): Part A | Date of first dose to disease progression or death due to any cause (Up to 25 Months) | The CBR is the percentage of participants with a best response of CR or PR, or Stable Disease (SD) for at least 6 months. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). * SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor. |
| Percentage of Participants With CBR: Part B | Date of first dose to disease progression or death due to any cause (Up to 25 Months) | The CBR is the percentage of participants with a best response of CR or PR, or SD for at least 6 months. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). * SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor. |
| Percentage of Participants With Disease Control Rate (DCR): Part A | Date of first dose to measured progressive disease (Up to 25 Months) | DCR: Percentage of participants with a best overall response of CR, PR, and SD. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). * SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor. |
| Percentage of Participants With DCR: Part B | Date of first dose to measured progressive disease (Up to 25 Months) | DCR: Percentage of participants with a best overall response of CR, PR, and SD. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). * SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor. |
| Progression-Free Survival (PFS): Part C | Date of first dose to progressive disease or death (Up to 25 Months) | Progression-free survival is measured as the time from first dose of study drug to progressive disease or death, whichever occurs first. PFS for Part C was reported. |
| Abemaciclib Tablet Acceptability | Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (21 Day Cycles) | Participants were evaluated for abemaciclib acceptability (palatability and ease of administration) by asking a question - " Was it easy or difficult for the study subject to swallow the abemaciclib today?" Participants or their caregivers or both could respond using the following possible answers: Very difficult, difficult, neither easy nor difficult, easy, or very easy. |
Countries
Australia, Belgium, France, Germany, Italy, Japan, Spain, United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A Cohort A1 Participants received:
* Abemaciclib: 70 mg/m², administered orally twice daily (BID).
* Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle.
* Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days. | 7 |
| Part A Cohort A-1 Participants received:
* Abemaciclib: 55 mg/m², administered orally BID.
* Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle.
* Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days. | 13 |
| Part B Cohort B1 Participants received:
* Abemaciclib: 70 mg/m², administered orally BID.
* Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days. | 3 |
| Part B Cohort B2 Participants received:
* Abemaciclib: 90 mg/m², administered orally BID.
* Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days. | 9 |
| Part B Cohort B3 Participants received:
* Abemaciclib: 115 mg/m², administered orally BID.
* Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days. | 3 |
| Part B Cohort B5 Participants received:
* Abemaciclib: 115 mg/m², administered orally BID.
* Temozolomide: 150 mg/m²/day, administered orally on Days 1-5 of each cycle.
Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days. | 11 |
| Part C Cohort C1 Participants received:
* Abemaciclib: 55 mg/m², administered orally BID.
* Irinotecan: 50 mg/m²/day, administered IV on Days 1-5 of each cycle.
* Temozolomide: 100 mg/m²/day, administered orally on Days 1-5 of each cycle.
* Dinutuximab: 17.5mg/m²/day, administered IV on Days 2-5 of each cycle.
* Granulocyte-macrophage colony-stimulating factor (GM-CSF): 250 μg/m²/day, administered subcutaneously (SC) on Days 6-12 of each cycle.
Treatment continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. Each cycle lasted 21 days. | 1 |
| Total | 47 |
Baseline characteristics
| Characteristic | Part B Cohort B5 | Total | Part C Cohort C1 | Part A Cohort A1 | Part A Cohort A-1 | Part B Cohort B1 | Part B Cohort B2 | Part B Cohort B3 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 9.8 years STANDARD_DEVIATION 4.5 | 11.4 years STANDARD_DEVIATION 3.9 | 7.00 years | 12.9 years STANDARD_DEVIATION 3.3 | 12.2 years STANDARD_DEVIATION 3.2 | 12.3 years STANDARD_DEVIATION 4.7 | 12.2 years STANDARD_DEVIATION 4.4 | 9.3 years STANDARD_DEVIATION 3.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 7 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 35 Participants | 1 Participants | 7 Participants | 7 Participants | 2 Participants | 8 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 0 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 |
| Race (NIH/OMB) Asian | 0 Participants | 7 Participants | 0 Participants | 3 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 36 Participants | 1 Participants | 4 Participants | 7 Participants | 2 Participants | 8 Participants | 3 Participants |
| Region of Enrollment France | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Germany | 1 Participants | 8 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants | 0 Participants |
| Region of Enrollment Italy | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 0 Participants | 5 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Region of Enrollment Spain | 10 Participants | 27 Participants | 0 Participants | 2 Participants | 7 Participants | 2 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 6 Participants | 23 Participants | 0 Participants | 2 Participants | 6 Participants | 2 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 24 Participants | 1 Participants | 5 Participants | 7 Participants | 1 Participants | 5 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 7 | 1 / 13 | 0 / 3 | 1 / 9 | 1 / 3 | 2 / 11 | 0 / 1 |
| other Total, other adverse events | 7 / 7 | 13 / 13 | 3 / 3 | 8 / 9 | 3 / 3 | 11 / 11 | 1 / 1 |
| serious Total, serious adverse events | 3 / 7 | 5 / 13 | 2 / 3 | 0 / 9 | 0 / 3 | 4 / 11 | 1 / 1 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of Abemaciclib in Part A
The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT.
Time frame: Cycle 1 (21 Days)
Population: All part A participants who received at least one dose of abemaciclib and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Maximum Tolerated Dose (MTD) of Abemaciclib in Part A | 55 mg/m² BID |
Primary
MTD of Abemaciclib in Part B
The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT.
Time frame: Cycle 1 (21 Days)
Population: All participants in Part B who received at least one dose of abemaciclib and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | MTD of Abemaciclib in Part B | NA mg/m² BID |
Primary
Number of Participants With Overall Response Rate (ORR) in Part C.
ORR: Number of participants with best response of Complete Response (CR), Partial Response (PR), or Minor Response (MR) per International Neuroblastoma Response Criteria (INRC). * CR is defined as complete response in all response components: * Primary Tumor: \<10 mm residual soft tissue primary site and complete resolution of MIBG-avid tumors * Soft tissue and bone metastatic response: nonprimary target and nontarget lesions \<10 mm and nodes identified as targets decreased to short axis \<10mm and MIBG-avid update of nonprimary lesions completely resolved * Bone marrow response: no tumor infiltration on reassessment; disappearance of all target lesions; * PR is defined as PR in \>1component and all other components are either CR, minimal disease (MD) (bone marrow only), PR (soft tissue or bone), or not involved (NI) and no components with progressive disease (PD). * MR is defined PR or CR in \>1 component and SD in \>1 component and no component with PD
Time frame: Date of first dose to disease progression or death (Up to 25 Months)
Population: All part C participants who received at least one dose of study drug. However, Part C was terminated early and only 1 participant was enrolled in this part.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A - Abemaciclib | Number of Participants With Overall Response Rate (ORR) in Part C. | 1 Participants |
Primary
Number or Participants With DLTs in Part B
A DLT was 1 of the following adverse events likely related to abemaciclib/combination and fulfils any 1 of the following criteria graded as per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0: * Any non-hematologic Grade (G) ≥3 toxicity, except: * G3 diarrhea lasting \<72 hr * Acute irinotecan-associated diarrhea lasting \<7 days * G≥3 nausea, vomiting, constipation that lasts \<72 hr * G3 mucositis/stomatitis lasting \<72 hr * G3 fever/infection * G≥3 electrolyte abnormality that lasts \<72 hr, is not complicated, and resolves spontaneously or responds to conventional medication; * G≥3 amylase/lipase that is not associated with symptoms/clinical manifestations of pancreatitis; or * AST/ALT elevation resolving to eligibility criteria within 7 days; * Hematologic toxicities considered a DLT: * A \>14-day Cycle 2 delay due to neutropenia/thrombocytopenia * G≥3 thrombocytopenia with significant bleeding; or * G≥ 4 neutropenic fever
Time frame: Cycle 1 (21 Day Cycle)
Population: All participants in Part B who received at least one dose of the study drug and had evaluable data for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A - Abemaciclib | Number or Participants With DLTs in Part B | 0 Participants |
| Part A Cohort A-1 | Number or Participants With DLTs in Part B | 1 Participants |
| Part B Cohort B3 | Number or Participants With DLTs in Part B | 0 Participants |
| Part B Cohort B5 | Number or Participants With DLTs in Part B | 1 Participants |
Primary
Number or Participants With Dose Limiting Toxicities (DLTs) in Part A
DLT was 1 of the following adverse events likely related to abemaciclib/combination and fulfils any 1 of the following criteria graded per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0: * Any non-hematologic Grade (G) ≥3 toxicity, except: * G3 diarrhea lasting \<72 hour (h) * Acute irinotecan-associated diarrhea lasting \<7 days * G≥3 nausea, vomiting, constipation that lasts \<72 h * G3 mucositis/stomatitis lasting \<72 h * G3 fever/infection * G≥3 electrolyte abnormality that lasts \<72 h, is not complicated, and resolves spontaneously or responds to conventional medication; * G≥3 amylase/lipase that is not associated with symptoms/clinical manifestations of pancreatitis; or * AST/ALT elevation resolving to eligibility criteria within 7 days; * Hematologic toxicities considered a DLT: * A \>14-day Cycle 2 delay due to neutropenia/thrombocytopenia * G≥3 thrombocytopenia with significant bleeding; or * G≥ 4 neutropenic fever
Time frame: Cycle 1 (21 Day Cycle)
Population: All participants in Part A who received at least one dose of the study drug and had evaluable data for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A - Abemaciclib | Number or Participants With Dose Limiting Toxicities (DLTs) in Part A | 3 Participants |
| Part A Cohort A-1 | Number or Participants With Dose Limiting Toxicities (DLTs) in Part A | 1 Participants |
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A
PK: (AUC0-tlast) was reported.
Time frame: Pre-dose, 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)
Population: All participants in Part A who received at least one dose of abemaciclib and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of study drug received.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A - Abemaciclib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A | Cycle 1, Day 1 | 730 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 33 |
| Part A - Abemaciclib | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A | Cycle 2, Day 1 | NA nanogram *hour per milliliter (ng*h/mL) | — |
| Part A Cohort A-1 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A | Cycle 1, Day 1 | 534 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 116 |
| Part A Cohort A-1 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A | Cycle 2, Day 1 | 757 nanogram *hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 100 |
Primary
PK: AUC0-tlast of Abemaciclib in Part B
PK: AUC0-tlast was reported.
Time frame: Pre-dose, 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)
Population: All participants in Part B who received at least one dose of abemaciclib and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of study drug received.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A - Abemaciclib | PK: AUC0-tlast of Abemaciclib in Part B | Cycle 1, Day 1 | 566 ng*h/mL | Geometric Coefficient of Variation 104 |
| Part A - Abemaciclib | PK: AUC0-tlast of Abemaciclib in Part B | Cycle 2, Day 1 | NA ng*h/mL | — |
| Part A Cohort A-1 | PK: AUC0-tlast of Abemaciclib in Part B | Cycle 1, Day 1 | 728 ng*h/mL | Geometric Coefficient of Variation 60 |
| Part A Cohort A-1 | PK: AUC0-tlast of Abemaciclib in Part B | Cycle 2, Day 1 | 600 ng*h/mL | Geometric Coefficient of Variation 27 |
| Part B Cohort B3 | PK: AUC0-tlast of Abemaciclib in Part B | Cycle 1, Day 1 | 728 ng*h/mL | Geometric Coefficient of Variation 77 |
| Part B Cohort B3 | PK: AUC0-tlast of Abemaciclib in Part B | Cycle 2, Day 1 | 1060 ng*h/mL | Geometric Coefficient of Variation 57 |
Primary
PK: (AUC0-tlast) of Irinotecan in Part A
PK: AUC0-tlast) was reported.
Time frame: 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)
Population: All Part A participants who received at least one dose of irinotecan and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of drug received.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A - Abemaciclib | PK: (AUC0-tlast) of Irinotecan in Part A | Cycle 1, Day 1 | 1450 ng*h/mL | Geometric Coefficient of Variation 37 |
| Part A - Abemaciclib | PK: (AUC0-tlast) of Irinotecan in Part A | Cycle 2, Day 1 | 1240 ng*h/mL | Geometric Coefficient of Variation 58 |
Primary
PK: (AUC0-tlast) of Temozolomide in Part A
PK: AUC0-tlast was reported.
Time frame: 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)
Population: All Part A participants who received at least one dose of temozolomide and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of drug received.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A - Abemaciclib | PK: (AUC0-tlast) of Temozolomide in Part A | Cycle 1, Day 1 | 14400 ng*h/mL | Geometric Coefficient of Variation 23 |
| Part A - Abemaciclib | PK: (AUC0-tlast) of Temozolomide in Part A | Cycle 2, Day 1 | 12200 ng*h/mL | Geometric Coefficient of Variation 44 |
Primary
PK: AUC0-tlast of Temozolomide in Part B
PK: AUC0-tlast was reported.
Time frame: 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)
Population: All Part B participants in who received at least one dose of temozolomide and had evaluable PK data. Per planned analysis, PK analysis was performed as per the dose of drug received.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A - Abemaciclib | PK: AUC0-tlast of Temozolomide in Part B | Cycle 1, Day 1 | 15800 ng*h/mL | Geometric Coefficient of Variation 19 |
| Part A - Abemaciclib | PK: AUC0-tlast of Temozolomide in Part B | Cycle 2, Day 1 | 15700 ng*h/mL | Geometric Coefficient of Variation 21 |
| Part A Cohort A-1 | PK: AUC0-tlast of Temozolomide in Part B | Cycle 2, Day 1 | 21100 ng*h/mL | Geometric Coefficient of Variation 43 |
| Part A Cohort A-1 | PK: AUC0-tlast of Temozolomide in Part B | Cycle 1, Day 1 | 24300 ng*h/mL | Geometric Coefficient of Variation 13 |
Primary
Recommended Phase 2 Dose (RP2D) of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A)
The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 50 mg/m²/day irinotecan and 100 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported.
Time frame: Cycles 1 and 2 (21 Day Cycles)
Population: All participants in Part A who received at least one dose of abemaciclib and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Recommended Phase 2 Dose (RP2D) of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A) | 55 milligrams/squared meters (mg/m²) BID |
Primary
RP2D of Abemaciclib in Combination With Temozolomide (Part B)
The RP2D of abemaciclib was determined based on the totality of safety, tolerability, and pharmacokinetic results. RP2D of abemaciclib in combination with 150 mg/m²/day temozolomide on days 1-5 of 21-day cycles was reported.
Time frame: Cycles 1 and 2 (21 Day Cycles)
Population: All participants in Part B who received at least one dose of abemaciclib and had evaluable data for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | RP2D of Abemaciclib in Combination With Temozolomide (Part B) | 115 mg/m² BID |
Secondary
Abemaciclib Tablet Acceptability
Participants were evaluated for abemaciclib acceptability (palatability and ease of administration) by asking a question - Was it easy or difficult for the study subject to swallow the abemaciclib today? Participants or their caregivers or both could respond using the following possible answers: Very difficult, difficult, neither easy nor difficult, easy, or very easy.
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (21 Day Cycles)
Population: All participants in Parts A and B, who received at least one dose of abemaciclib and had evaluable data for this outcome. Per protocol, data were summarized by responses provided by participants, and/or caregivers on the acceptability of the abemaciclib received on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A - Abemaciclib | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part A - Abemaciclib | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part A - Abemaciclib | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 2 Participants |
| Part A - Abemaciclib | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part A - Abemaciclib | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 1 Participants |
| Part A Cohort A-1 | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 1 Participants |
| Part A Cohort A-1 | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1 | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part A Cohort A-1 | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1 | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 2 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 3 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 3 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 4 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 4 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 4 Participants |
| Part B Cohort B5 | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 2 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 6 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 4 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part A Cohort A-1(Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 6 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 4 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 6 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 3 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 1 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 4 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 5 Participants |
| Part A Cohort A-1(Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 3 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 1 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 0 Participants |
| Part B Cohort B1 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 2 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 1 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 2 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B1 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 1 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 3 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 3 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 2 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 2 Participants |
| Part B Cohort B2 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 5 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 1 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 5 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 1 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 3 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 1 Participants |
| Part B Cohort B2 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 1 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 1 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 3 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 3 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 3 Participants |
| Part B Cohort B3 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 2 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 3 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 1 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 6 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 1 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 4 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B5 (Caregiver Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 1 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 1 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 6 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 1 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 1 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 1 Day 15) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 8 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very easy to swallow tablet | 9 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Neither easy nor difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Easy to swallow tablet | 0 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Difficult to swallow tablet | 0 Participants |
| Part B Cohort B5 (Participant Responses - Cycle 2 Day 1) | Abemaciclib Tablet Acceptability | Very difficult to swallow tablet | 0 Participants |
Secondary
Duration of Response (DoR): Part C
DoR is the time between first evidence of CR, PR or MR and disease progression or death due to any cause. CR, PR, and MR was as per International Neuroblastoma Response Criteria (INRC). \- CR is defined as complete response in all response components: Primary Tumor: \<10 mm residual soft tissue primary site and complete resolution of MIBG-avid tumors Soft tissue and bone metastatic response: nonprimary target and nontarget lesions \<10 mm and nodes identified as targets decreased to short axis \<10mm and MIBG-avid update of nonprimary lesions completely resolved Bone marrow response: no tumor infiltration on reassessment; disappearance of all target lesions; * PR is defined as PR in \>1 component and all other components are either CR, minimal disease (MD) (bone marrow only), PR (soft tissue or bone), or not involved (NI) and no components with progressive disease (PD). * MR is defined PR or CR in \>1 component and SD in \>1 component and no component with PD
Time frame: Date of first evidence of a CR, PR, or MR to date of objective disease progression or death due to any cause (Up to 25 Months)
Population: All participants in Part C who received at least one dose of the study drug and had evaluable data for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A - Abemaciclib | Duration of Response (DoR): Part C | 1.61 Months |
Secondary
Duration of Response (DoR): Parts A and B.
DoR is the time between first evidence of CR or PR and disease progression or death due to any cause. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
Time frame: Date of first evidence of a CR or PR to date of objective disease progression or death due to any cause (Up to 25 Months)
Population: All participants in Parts A and B who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A Cohort A-1 | Duration of Response (DoR): Parts A and B. | 22.59 Months |
| Part B Cohort B3 | Duration of Response (DoR): Parts A and B. | 7.82 Months |
| Part B Cohort B5 | Duration of Response (DoR): Parts A and B. | 0.03 Months |
Secondary
Percentage of Participants With CBR: Part B
The CBR is the percentage of participants with a best response of CR or PR, or SD for at least 6 months. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). * SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.
Time frame: Date of first dose to disease progression or death due to any cause (Up to 25 Months)
Population: All participants in Part B who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Percentage of Participants With CBR: Part B | 33.3 Percentage of participants |
| Part A Cohort A-1 | Percentage of Participants With CBR: Part B | 0 Percentage of participants |
| Part B Cohort B3 | Percentage of Participants With CBR: Part B | 33.3 Percentage of participants |
| Part B Cohort B5 | Percentage of Participants With CBR: Part B | 18.2 Percentage of participants |
Secondary
Percentage of Participants With Clinical Benefit Rate (CBR): Part A
The CBR is the percentage of participants with a best response of CR or PR, or Stable Disease (SD) for at least 6 months. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). * SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.
Time frame: Date of first dose to disease progression or death due to any cause (Up to 25 Months)
Population: All participants in Part A who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Percentage of Participants With Clinical Benefit Rate (CBR): Part A | 14.3 Percentage of participants |
| Part A Cohort A-1 | Percentage of Participants With Clinical Benefit Rate (CBR): Part A | 30.8 Percentage of participants |
Secondary
Percentage of Participants With DCR: Part B
DCR: Percentage of participants with a best overall response of CR, PR, and SD. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). * SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.
Time frame: Date of first dose to measured progressive disease (Up to 25 Months)
Population: All participants in Part B who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Percentage of Participants With DCR: Part B | 33.3 Percentage of participants |
| Part A Cohort A-1 | Percentage of Participants With DCR: Part B | 55.6 Percentage of participants |
| Part B Cohort B3 | Percentage of Participants With DCR: Part B | 100 Percentage of participants |
| Part B Cohort B5 | Percentage of Participants With DCR: Part B | 36.4 Percentage of participants |
Secondary
Percentage of Participants With Disease Control Rate (DCR): Part A
DCR: Percentage of participants with a best overall response of CR, PR, and SD. RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO). * SD is neither sufficient shrinkage nor sufficient increase in the size of the tumor.
Time frame: Date of first dose to measured progressive disease (Up to 25 Months)
Population: All participants in Part A who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Percentage of Participants With Disease Control Rate (DCR): Part A | 71.4 Percentage of participants |
| Part A Cohort A-1 | Percentage of Participants With Disease Control Rate (DCR): Part A | 53.8 Percentage of participants |
Secondary
Percentage of Participants With ORR: Part B
ORR: Percentage of participants with best response of CR or PR per Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO). RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
Time frame: Date of first dose to disease progression or death (Up to 25 Months)
Population: All participants in Part B who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Percentage of Participants With ORR: Part B | 0 Percentage of participants |
| Part A Cohort A-1 | Percentage of Participants With ORR: Part B | 0 Percentage of participants |
| Part B Cohort B3 | Percentage of Participants With ORR: Part B | 33.3 Percentage of participants |
| Part B Cohort B5 | Percentage of Participants With ORR: Part B | 18.2 Percentage of participants |
Secondary
Percentage of Participants With Overall Response Rate (ORR): Part A
ORR: Percentage of participants with best response of CR or PR per Response Evaluation Criteria in Solid Tumors (RECIST) or Response Assessment in Neuro-Oncology (RANO). RECIST was used for solid tumors and RANO was used for brain tumors. * CR is defined as the disappearance of all target lesions (RECIST) and disappearance of all enhancing measurable and non-measurable disease, no new lesions; stable or improved non-enhancing lesions; and patient must be off corticosteroids and stable or improved clinically (RANO). * PR is defined as a 30% decrease in the sum of diameters of target lesions (RECIST) and \>50% decrease in the sum of products of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, no new lesions, stable/improved non-enhancing lesions on same or lower dose of corticosteroids and patient is stable or improved clinically (RANO).
Time frame: Date of first dose to disease progression or death (Up to 25 Months)
Population: All participants in Part A who received at least one dose of the study drug and had evaluable data for this outcome. Per pre-specified statistical analysis plan, analysis was performed as per the study treatments received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Percentage of Participants With Overall Response Rate (ORR): Part A | 0 Percentage of participants |
| Part A Cohort A-1 | Percentage of Participants With Overall Response Rate (ORR): Part A | 7.7 Percentage of participants |
Secondary
Progression-Free Survival (PFS): Part C
Progression-free survival is measured as the time from first dose of study drug to progressive disease or death, whichever occurs first. PFS for Part C was reported.
Time frame: Date of first dose to progressive disease or death (Up to 25 Months)
Population: All part C participants who received at least one dose of study drug. However, Part C was terminated early and only 1 participant was enrolled in this part.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A - Abemaciclib | Progression-Free Survival (PFS): Part C | 2.9 Months |