A Phase 1b/2 Study of Abemaciclib Plus Chemotherapy and/or Chemoimmunotherapy in Pediatric and Young Adult Patients with Relapsed/Refractory Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eli Lilly & Co.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Nov 2020 → 19 Aug 2025

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-506778-11-00

EudraCT number

2019-002931-27

WHO UTN

U1111-1301-2809

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

To determine the optimal RP2D for abemaciclib in patients with relapsed/refractory solid tumors:

- in combination with irinotecan and temozolomide (Part A)

- in combination with temozolomide (Part B)

Conditions and MedDRA coding

Relapsed/Refractory Solid Tumors

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002342-PIP02-18, EMEA-002342-PIP01-18

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 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.
2. 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.
3. 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 14

1. Received allogenic bone marrow or solid organ transplant.
2. Received live vaccination.
3. Intolerability or hypersensitivity to any of the study treatments or its components.
4. 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.
5. Pregnant or breastfeeding.
6. Active systemic infections.
7. Serious and/or uncontrolled preexisting medical condition(s) that would preclude participation in this study.
8. Parts A and C only: Have a bowel obstruction.
9. 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.
10. Received prior treatment with cyclin-dependent kinase (CDK) 4 & 6 inhibitor
11. Part C only: Received prior systemic therapy for relapsed/refractory neuroblastoma.
12. Part C only, have received prior anti-GD2 therapy during induction phase.
13. Currently enrolled in any other clinical study involving an investigational product or non-approved use of a drug or device.
14. Has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Dose Limiting Toxicity (DLT)
2. Maximum Tolerated Doses (MTD)
3. PK (plasma concentrations of abemaciclib, irinotecan, and temozolomide)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eli Lilly & Co.

Sponsor organisation

Eli Lilly & Co.

Address

1 Lilly Corporate Center

City

Indianapolis

Postcode

46285-0001

Country

United States

Scientific contact point

Organisation

Eli Lilly & Co.

Contact name

Lilly Clinical Trials information desk

Public contact point

Organisation

Eli Lilly & Co.

Contact name

Lilly Clinical Trials information desk

Third parties 8

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications