A Study of Abemaciclib (LY2835219) in Combination With Other Anti-Cancer Treatments in Children and Young Adult Participants With Solid Tumors, Including Neuroblastoma

NCT04238819 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: 16950I3Y-MC-JPCS2019-002931-272023-506778-11-00
• Study Type: interventional
• Target: 47
• Locations: 8 countries
• Sites: 25

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.

Conditions

Relapsed Solid Tumor; Refractory Solid Tumor

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

Outcome Measures

Primary Outcomes (12)

• 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.

  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

  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.

  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.

  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.

  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.

  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.

  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

  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.

  Cycle 1 (21 Days)

• PK: AUC0-tlast of Abemaciclib in Part B

  PK: AUC0-tlast was reported.

  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.

  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

  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

  Date of first dose to disease progression or death (Up to 25 Months)

• Percentage of Participants With ORR: Part B

  Date of first dose to disease progression or death (Up to 25 Months)

• 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)

• 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)

• 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)

Study Arms (7)

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.

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.

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.

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.

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.

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.

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.

Drug: Abemaciclib; Drug: Irinotecan; Drug: Temozolomide; Drug: Dinutuximab; Drug: GM-CSF

Interventions

Abemaciclib DRUG

Administered orally

Also known as: LY2835219

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

Irinotecan DRUG

Administered IV

Part A Cohort A-1; Part A Cohort A1; Part C Cohort C1

Temozolomide DRUG

Administered orally

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

Dinutuximab DRUG

Administered IV

Part C Cohort C1

GM-CSF DRUG

Administered SC

Part C Cohort C1

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (25)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

The Regents of the University of California - Los Angeles (UCLA Pediatrics)

Los Angeles, California, 90095-1752, United States

Location

Kaiser Permanente Oakland

Oakland, California, 94611, United States

Location

Kaiser Permanente Roseville

Roseville, California, 95661, United States

Location

Kaiser Permanente Santa Clara

Santa Clara, California, 95051, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

Cohen Children's Medical Center

New Hyde Park, New York, 11040, United States

Location

Atrium Health - Carolinas Medical Center

Charlotte, North Carolina, 28203, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, 19104, United States

Location

Lifespan Cancer Institute

Providence, Rhode Island, 02906, United States

Location

Perth Children's Hospital

Perth, Western Australia, 6009, Australia

Location

UZ Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Centre Leon Berard

Lyon, Rhône, 69373 CEDEX 08, France

Location

Gustave Roussy

Villejuif, Val-de-Marne, 94800, France

Location

Institut Curie

Paris, 75248, France

Location

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitaetsklinikum Essen

Essen, North Rhine-Westphalia, 45122, Germany

Location

Charité Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Fondazione Policlinico Universitario Agostino Gemelli

Rome, Lazio, 168, Italy

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

Location

Hospital Universitari Vall d'Hebron

Barcelona, Barcelona [Barcelona], 8035, Spain

Location

Hospital Infantil Universitario Niño Jesús

Madrid, Madrid, Comunidad de, 28009, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

Location

Related Links

• 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 Tumors

MeSH Terms

Conditions

Sarcoma, Ewing; Neuroblastoma; Rhabdoid Tumor; Rhabdomyosarcoma; Osteosarcoma; Brain Neoplasms; Glioblastoma; Glioma; Diffuse Intrinsic Pontine Glioma; Medulloblastoma; Ependymoma

Interventions

abemaciclib; Irinotecan; Temozolomide; dinutuximab; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Complex and Mixed; Myosarcoma; Neoplasms, Muscle Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma; Brain Stem Neoplasms; Infratentorial Neoplasms

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2020
• First Posted: January 23, 2020
• Study Start: November 9, 2020
• Primary Completion: March 15, 2024
• Study Completion: August 19, 2025
• Last Updated: March 2, 2026
• Results First Posted: August 6, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

DE (3); FR (3); IT (1); JP (1); ES (3); AU (1); BE (1); US (12)