Clinical Trial Finder

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.

Arms

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.

Experimental: 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.

Interventions

Drug: - Abemaciclib

Administered orally

Drug: - Irinotecan

Administered IV

Drug: - Temozolomide

Administered orally

Drug: - Dinutuximab

Administered IV

Drug: - GM-CSF

Administered SC