Relapsed Solid TumorPhase 1/2NCT04238819
A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma
A Phase 1/2 study testing Abemaciclib, Irinotecan and Temozolomide in people with Relapsed Solid Tumor and Refractory Solid Tumor, run by Eli Lilly and Company at 25 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Relapsed Solid Tumor, Refractory Solid Tumor
- What is being tested?
- Abemaciclib, Irinotecan and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 25 sitesin 8 countries
- Study dates
- 9 Nov 2020to 19 Aug 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
25 sites in 8 countries.
25 sites in 8 countries
United States12 sites
Atrium Health - Carolinas Medical Center
Charlotte, North Carolina, 28203
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Spectrum Health
Grand Rapids, Michigan, 49503
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
The Regents of the University of California - Los Angeles (UCLA Pediatrics)
Los Angeles, California, 90095-1752
Cohen Children's Medical Center
New Hyde Park, New York, 11040
Kaiser Permanente Oakland
Oakland, California, 94611
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Lifespan Cancer Institute
Providence, Rhode Island, 02906
Kaiser Permanente Roseville
Roseville, California, 95661
Kaiser Permanente Santa Clara
Santa Clara, California, 95051
France3 sites
Centre Leon Berard
Lyon, Rhône, 69373 CEDEX 08
Institut Curie
Paris, 75248
Gustave Roussy
Villejuif, Val-de-Marne, 94800
Germany3 sites
Charité Campus Virchow-Klinikum
Berlin, 13353
Universitaetsklinikum Essen
Essen, North Rhine-Westphalia, 45122
Universitaetsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120
Spain3 sites
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [Barcelona], 8035
Hospital Infantil Universitario Niño Jesús
Madrid, Madrid, Comunidad de, 28009
Hospital Universitari i Politecnic La Fe
Valencia, 46026
Italy1 site
Fondazione Policlinico Universitario Agostino Gemelli
Rome, Lazio, 168
About this study
Official title: A Phase 1b/2 Study of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A) and Abemaciclib in Combination With Temozolomide (Part B) in Pediatric and Young Adult Patients With Relapsed/Refractory Solid Tumors and Abemaciclib in Combination With Dinutuximab, GM-CSF, Irinotecan, and Temozolomide in Pediatric and Young Adult Patients With Relapsed/Refractory Neuroblastoma (Part C)
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.
- Conditions
- Relapsed Solid Tumor, Refractory Solid Tumor
- Being tested
- Abemaciclib, Irinotecan, Temozolomide, Dinutuximab, GM-CSF
- 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
- Medical subject headings
- Sarcoma, Ewing, Neuroblastoma, Rhabdoid Tumor, Rhabdomyosarcoma, Osteosarcoma, Brain Neoplasms, Glioblastoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbemaciclibDrug
Also called LY2835219
Administered orally
IrinotecanDrug
Administered IV
TemozolomideDrug
Administered orally
DinutuximabDrug
Administered IV
GM-CSFDrug
Administered SC
| Study group | Role | What they receive |
|---|---|---|
| Part A Cohort A1 | Experimental | 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. Receives: Drug: Abemaciclib; Drug: Irinotecan; Drug: Temozolomide |
| Part A Cohort A-1 | Experimental | 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. Receives: Drug: Abemaciclib; Drug: Irinotecan; Drug: Temozolomide |
| Part B Cohort B1 | Experimental | 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. Receives: Drug: Abemaciclib; Drug: Temozolomide |
| Part B Cohort B2 | Experimental | 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. Receives: Drug: Abemaciclib; Drug: Temozolomide |
| Part B Cohort B3 | Experimental | 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. Receives: Drug: Abemaciclib; Drug: Temozolomide |
| Part B Cohort B5 | Experimental | 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. Receives: Drug: Abemaciclib; Drug: Temozolomide |
| Part C Cohort C1 | Experimental | 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. Receives: Drug: Abemaciclib; Drug: Irinotecan; Drug: Temozolomide; Drug: Dinutuximab; Drug: GM-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Cycles 1 and 2 (21 Day Cycles)
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
Measured: Cycle 1 (21 Day Cycle)
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.
Measured: Cycle 1 (21 Days)
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.
Measured: 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) of Irinotecan in Part A
PK: AUC0-tlast) was reported.
Measured: 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)
PK: (AUC0-tlast) of Temozolomide in Part A
PK: AUC0-tlast was reported.
Measured: 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)
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.
Measured: Cycles 1 and 2 (21 Day Cycles)
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
Measured: Cycle 1 (21 Day Cycle)
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.
Measured: Cycle 1 (21 Days)
PK: AUC0-tlast of Abemaciclib in Part B
PK: AUC0-tlast was reported.
Measured: 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 of Temozolomide in Part B
PK: AUC0-tlast was reported.
Measured: 1, 2.5, 4, and 6 hours post Day 1 dose of Cycle 1 and Cycle 2 (21 Day Cycle)
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
Measured: Date of first dose to disease progression or death (Up to 25 Months)
Secondary outcomes (10)
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).
Measured: Date of first dose to disease progression or death (Up to 25 Months)
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).
Measured: Date of first dose to disease progression or death (Up to 25 Months)
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).
Measured: 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)
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
Measured: 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)
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.
Measured: Date of first dose to disease progression or death due to any cause (Up to 25 Months)
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.
Measured: Date of first dose to disease progression or death due to any cause (Up to 25 Months)
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.
Measured: Date of first dose to measured progressive disease (Up to 25 Months)
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.
Measured: Date of first dose to measured progressive disease (Up to 25 Months)
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.
Measured: Date of first dose to progressive disease or death (Up to 25 Months)
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.
Measured: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (21 Day Cycles)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2020
- Study start9 Nov 2020
- Primary completion15 Mar 2024
- Study completion19 Aug 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed Solid TumorStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04238819
- Sponsor's protocol ID
- 16950
- Other IDs
- I3Y-MC-JPCS, 2019-002931-27, 2023-506778-11-00, 2023, 2019
- Status last verified
- Feb 2026
- First submitted
- 22 Jan 2020
- Last updated
- 2 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A) and Abemaciclib in Combination With Temozolomide (Part B) in Pediatric and Young Adult Patients With Relapsed/Refractory Solid Tumors and Abemaciclib in Combination With Dinutuximab, GM-CSF, Irinotecan, and Temozolomide in Pediatric and Young Adult Patients With Relapsed/Refractory Neuroblastoma (Part C)
- ClinicalTrials.gov ID
- NCT04238819
- Acronym / sponsor ID
- 16950
- Conditions
- Relapsed Solid Tumor, Refractory Solid Tumor
- Keywords
- CDK4, CDK6, Ewing's sarcoma, Neuroblastoma, Recurrent neuroblastoma, Malignant rhabdoid tumor, Rhabdomyosarcoma, Osteosarcoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 9 Nov 2020 (actual)
- Primary completion
- 15 Mar 2024 (actual)
- Study completion
- 19 Aug 2025 (actual)
- First posted
- 23 Jan 2020 (actual)
- Results
- Posted 6 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Part A Cohort A1 | Experimental | Drug: Abemaciclib, Drug: Irinotecan, Drug: TemozolomideParticipants 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. |
| Part A Cohort A-1 | Experimental | Drug: Abemaciclib, Drug: Irinotecan, Drug: TemozolomideParticipants 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. |
| Part B Cohort B1 | Experimental | Drug: Abemaciclib, Drug: TemozolomideParticipants 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. |
| Part B Cohort B2 | Experimental | Drug: Abemaciclib, Drug: TemozolomideParticipants 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. |
| Part B Cohort B3 | Experimental | Drug: Abemaciclib, Drug: TemozolomideParticipants 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. |
| Part B Cohort B5 | Experimental | Drug: Abemaciclib, Drug: TemozolomideParticipants 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. |
| Part C Cohort C1 | Experimental | Drug: Abemaciclib, Drug: Irinotecan, Drug: Temozolomide, Drug: Dinutuximab, Drug: GM-CSFParticipants 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. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (19 listed)
- Parts A and B only:
- Part C only:
- All Parts
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AbemaciclibAlso: LY2835219Administered orally | Drug | Part A Cohort A-1, Part A Cohort A1, Part B Cohort B1, Part B Cohort B2, Part B Cohort B3, Part B Cohort B5, Part C Cohort C1 |
| IrinotecanAdministered IV | Drug | Part A Cohort A-1, Part A Cohort A1, Part C Cohort C1 |
| TemozolomideAdministered orally | Drug | Part A Cohort A-1, Part A Cohort A1, Part B Cohort B1, Part B Cohort B2, Part B Cohort B3, Part B Cohort B5, Part C Cohort C1 |
| DinutuximabAdministered IV | Drug | Part C Cohort C1 |
| GM-CSFAdministered SC | Drug | Part C Cohort C1 |
Primary outcome
Recommended Phase 2 Dose (RP2D) of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A)
Time frame: 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
Time frame: 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
Maximum Tolerated Dose (MTD) of Abemaciclib in Part A
Time frame: Cycle 1 (21 Days)
The MTD was defined as the highest dose level at which less than 33% of participants experienced a DLT.
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Tlast (AUC0-tlast) of Abemaciclib in Part A
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
10 secondary outcomes
Percentage of Participants With Overall Response Rate (ORR): Part A
Time frame: Date of first dose to disease progression or death (Up to 25 Months)
Percentage of Participants With ORR: Part B
Time frame: Date of first dose to disease progression or death (Up to 25 Months)
Duration of Response (DoR): Parts A and B.
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)
Duration of Response (DoR): Part C
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)
Percentage of Participants With Clinical Benefit Rate (CBR): Part A
Time frame: Date of first dose to disease progression or death due to any cause (Up to 25 Months)
Percentage of Participants With CBR: Part B
Time frame: Date of first dose to disease progression or death due to any cause (Up to 25 Months)
Percentage of Participants With Disease Control Rate (DCR): Part A
Time frame: Date of first dose to measured progressive disease (Up to 25 Months)
Percentage of Participants With DCR: Part B
Time frame: Date of first dose to measured progressive disease (Up to 25 Months)
Progression-Free Survival (PFS): Part C
Time frame: Date of first dose to progressive disease or death (Up to 25 Months)
Abemaciclib Tablet Acceptability
Time frame: Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 (21 Day Cycles)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Study of Abemaciclib (LY2835219) in Combination With Temozolomide and Irinotecan and Abemaciclib in Combination With Temozolomide in Children and Young Adult Participants With Solid TumorsLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Call 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) study director
Eli Lilly and Company
25 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Abemaciclib, Irinotecan and Temozolomide in people with Relapsed Solid Tumor and Refractory Solid Tumor, run by Eli Lilly and Company at 25 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, France, Germany, Spain, Australia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended Phase 2 Dose (RP2D) of Abemaciclib in Combination With Irinotecan and Temozolomide (Part A) (time frame: Cycles 1 and 2 (21 Day Cycles)). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2026.