Abemaciclib Combination Therapy for Neuroblastoma

Recruiting at 65 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eli Lilly and Company

Must not be taking: CYP3A inhibitors, UGT1A1 inhibitors

Disqualifiers: Transplant, Pregnancy, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 months

47 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a combination of drugs, including abemaciclib (a cancer treatment drug), can safely and effectively treat solid tumors like neuroblastoma that resisted previous treatments. Participants will receive various drug combinations to determine which best stops the cancer cells. The trial specifically seeks children and young adults with solid tumors unresponsive to standard cancer treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that patients usually tolerate abemaciclib well, with most side effects being mild to moderate. In studies, diarrhea was the most common side effect, generally manageable and resolving over time. Safety data from patients using abemaciclib with irinotecan and temozolomide also indicate that the combination is generally safe, with no new safety issues identified.

Furthermore, studies on the combination of abemaciclib, irinotecan, temozolomide, and dinutuximab suggest that adding dinutuximab does not significantly alter the treatment's safety. While most side effects were mild, some patients experienced more severe reactions, which were expected given the treatments.

Since this study is in its early stages, it primarily focuses on ensuring the treatment's safety. Much remains to be learned about patient responses, but current evidence suggests it is generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Abemaciclib combination therapy for neuroblastoma because it offers a fresh approach compared to existing treatments like chemotherapy and radiation. Abemaciclib is a CDK4/6 inhibitor, which means it targets specific proteins involved in cell division, potentially halting cancer cell growth more precisely than traditional treatments. Additionally, this combination therapy includes drugs like Dinutuximab, which targets GD2, a molecule found on neuroblastoma cells, enhancing the immune response against the cancer. These unique mechanisms of action provide hope for a more effective treatment with possibly fewer side effects.

What evidence suggests that this trial's treatments could be effective for neuroblastoma?

This trial tests various combinations of Abemaciclib with other drugs to evaluate their effectiveness against neuroblastoma. One treatment arm combines Abemaciclib with Irinotecan and Temozolomide; research has shown this combination can be effective against some difficult-to-treat tumors. Another arm tests Abemaciclib with Temozolomide, which studies suggest might help with challenging cases like high-grade glioma, a type of brain cancer. Additionally, the trial includes an arm where Dinutuximab is added to the combination of Abemaciclib, Irinotecan, and Temozolomide, believed to enhance the fight against neuroblastoma, a cancer mostly affecting children. These combinations are being tested to determine their potential as effective options for those whose cancer hasn't responded to other treatments. ^{1 6 7 8 9}

Who Is on the Research Team?

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)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for children and young adults up to age 21 with solid tumors, including neuroblastoma, that haven't improved after treatment. They must be able to swallow pills, have a body weight over 10 kg, not be pregnant or breastfeeding, and agree to use contraception. Those with certain other health conditions or treatments are excluded.

Inclusion Criteria

I and my caregiver can commit to the full duration of the trial.

Participants must have measurable or evaluable disease by RECIST v1.1 or RANO.

I can swallow.

Exclusion Criteria

I have received a bone marrow or organ transplant from another person.

Serious and/or uncontrolled preexisting medical condition(s) that would preclude participation in this study.

Has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib in combination with other drugs such as irinotecan and temozolomide, with cycles lasting 21 days

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Dinutuximab
• Irinotecan
• Temozolomide

Trial Overview The study tests the safety and effectiveness of abemaciclib combined with other anti-cancer drugs (Irinotecan, Temozolomide, Dinutuximab, GM-CSF) in participants who have cancer that's resistant to previous treatments. The trial will last up to two years per participant.

How Is the Trial Designed?

Group I: Part C Cohort C1 Experimental Treatment 5 Interventions

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.

Group II: Part B Cohort B5 Experimental Treatment 2 Interventions

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.

Group III: Part B Cohort B3 Experimental Treatment 2 Interventions

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.

Group IV: Part B Cohort B2 Experimental Treatment 2 Interventions

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.

Group V: Part B Cohort B1 Experimental Treatment 2 Interventions

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.

Group VI: Part A Cohort A1 Experimental Treatment 3 Interventions

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.

Group VII: Part A Cohort A-1 Experimental Treatment 3 Interventions

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.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Citations

1. trials.lilly.com trials.lilly.com/en-US/trial/281358

A Study of Abemaciclib (LY2835219) in Combination With ... The study's purpose is to see if the drug abemaciclib is safe and effective in combination with temozolomide and irinotecan (Part A)

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04238819

NCT04238819 | A Study of Abemaciclib (LY2835219) in ... The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.10039

Recommended phase 2 dose (RP2D) for abemaciclib in ... The RP2D of abemaciclib is 55mg/m 2 BID in combination with IRN and TMZ. This combination appears tolerable with plasma concentrations within the range ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT400644

A randomized, open-label, phase 2 study evaluating ... This study, NCT05440786, will evaluate the potential benefit of adding abemaciclib to irinotecan plus temozolomide for the treatment of relapsed/refractory ES.

5. clinicaltrials.eu clinicaltrials.eu/trial/study-of-abemaciclib-with-irinotecan-and-temozolomide-for-children-and-young-adults-with-relapsed-or-refractory-solid-tumors/

Study of Abemaciclib with Irinotecan and Temozolomide for ... This study tests the effectiveness of Abemaciclib in combination with Irinotecan and Temozolomide for treating children and young adults ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-01489

A Study of Abemaciclib (LY2835219) in Combination With ... The study's purpose is to see if the drug, abemaciclib, is safe and effective when given with other drugs to kill cancer cells.

7. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.TPS10068

Phase 1b/2 study of abemaciclib combined with ... TPS10068. Background: Survival for high-risk neuroblastoma (NBL) remains poor with over 50% of patients experiencing disease relapse.

8. sciencedirect.com sciencedirect.com/science/article/pii/S0923753425049488

Overall Survival with Abemaciclib in Early Breast Cancer Patient reported outcomes findings confirm a tolerable and reversible toxicity profile. The long-term safety data compiled did not support any ...

9. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601722/

Clinical Review - Abemaciclib (Verzenio) - NCBI Bookshelf - NIH As of the final primary outcome (IDFS) analysis (July 8, 2020), 97.9% of patients in the abemaciclib plus ET arm and 87.2% of patients in the ET arm ...