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

Lilly

Status and phase: Completed; Phase 2; Phase 1

Conditions: Relapsed Solid Tumor; Refractory Solid Tumor

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT04238819

2023-506778-11-00 (Other Identifier)

2019-002931-27 (EudraCT Number)

I3Y-MC-JPCS (Other Identifier)

16950 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 47 patients

Sex: All

Ages: Under 21 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 7 patient groups

Part A Cohort A1

Experimental group

Description:

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.

Treatment:

Drug: Irinotecan

Drug: Temozolomide

Drug: Abemaciclib

Part A Cohort A-1

Experimental group

Description:

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.

Treatment:

Drug: Irinotecan

Drug: Temozolomide

Drug: Abemaciclib

Part B Cohort B1

Experimental group

Description:

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.

Treatment:

Drug: Temozolomide

Drug: Abemaciclib

Part B Cohort B2

Experimental group

Description:

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.

Treatment:

Drug: Temozolomide

Drug: Abemaciclib

Part B Cohort B3

Experimental group

Description:

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.

Treatment:

Drug: Temozolomide

Drug: Abemaciclib

Part B Cohort B5

Experimental group

Description:

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.

Treatment:

Drug: Temozolomide

Drug: Abemaciclib

Part C Cohort C1

Experimental group

Description:

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.

Treatment:

Drug: Irinotecan

Drug: Dinutuximab

Drug: Temozolomide

Drug: Abemaciclib

Drug: GM-CSF