Abemaciclib for Lung Cancer

(JUNIPER Trial)

Not currently recruiting at 272 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Must not be taking: CDK4/6 inhibitors

Disqualifiers: Unapproved drugs, Cardiac history, Unstable CNS, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 28-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a drug called abemaciclib for individuals with non-small cell lung cancer (NSCLC). Participants will receive either abemaciclib or another treatment, erlotinib, to compare their effects. Suitable candidates have stage IV NSCLC with specific genetic mutations and have previously tried certain treatments without success. As a Phase 3 trial, this study is the final step before potential FDA approval, providing participants an opportunity to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop all previous cancer therapies, including chemotherapy, radiotherapy, and immunotherapy, for at least 21 days for certain drugs or 14 days for others before starting the study drug. The protocol does not specify about other non-cancer medications, so it's best to discuss with the trial team.

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

Research has shown that abemaciclib is generally safe. In previous studies, patients tolerated it well when taken twice a day. Some studies combined it with other cancer drugs, and most participants still found it manageable. Common side effects included fatigue, diarrhea, and nausea, but these were usually mild.

The FDA has already approved abemaciclib for some other conditions, indicating its safety for those uses. However, this does not guarantee the same outcome for lung cancer. Every drug affects individuals differently, and side effects can vary. Prospective trial participants should consult a healthcare provider to discuss potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Abemaciclib is unique because it targets cyclin-dependent kinases 4 and 6 (CDK4/6), which are crucial for cell division. Most treatments for lung cancer, like chemotherapy or erlotinib, focus on other pathways, but abemaciclib specifically interrupts the cell cycle, potentially stopping cancer cells from multiplying. Researchers are excited about abemaciclib because it offers a new mechanism of action and could be more effective in controlling tumor growth, especially for patients who might not respond well to existing therapies.

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

In this trial, participants will receive either Abemaciclib or Erlotinib. Research has shown that Abemaciclib may help treat certain types of cancer. The JUNIPER study tested Abemaciclib on patients with non-small cell lung cancer (NSCLC), but it did not improve survival for those with the KRAS mutation. Other studies have found that Abemaciclib can slow cancer growth by targeting proteins that aid cancer cell division. This suggests it might benefit lung cancer patients, although results can vary based on individual patient characteristics. Overall, Abemaciclib has shown potential, but its effectiveness may depend on personal factors. ^{2 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 adults with stage IV non-small cell lung cancer (NSCLC) who have specific KRAS mutations and whose disease has worsened after platinum-based chemotherapy. They must be in good physical condition, not have received certain unapproved drugs recently, and cannot have unstable brain metastases or a history of serious heart rhythm problems.

Inclusion Criteria

My cancer has a specific KRAS mutation in codons 12 or 13.

My cancer has worsened after platinum chemotherapy and one other treatment, or I can't have more standard treatments.

Have measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Exclusion Criteria

I have a history of fainting, irregular heartbeats, or sudden cardiac arrest.

I haven't taken any unapproved drugs within the last 3 weeks.

My brain scans show stable cancer spread to the brain, not needing steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 200 mg abemaciclib every 12 hours or 150 mg erlotinib every 24 hours, both with best supportive care, in 28-day cycles

28-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 32 months

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Erlotinib

Trial Overview The study is testing the safety and effectiveness of abemaciclib, a new drug, on participants with NSCLC who carry certain KRAS mutations. The trial will also involve erlotinib to see how well these treatments work together against this type of lung cancer.

How Is the Trial Designed?

Group I: Abemaciclib Experimental Treatment 1 Intervention

200 milligrams (mg) abemaciclib administered, orally, every 12 hours plus best supportive care (BSC) on Days 1 to 28 (28 day cycles).

Group II: Erlotinib Active Control 1 Intervention

150 mg erlotinib administered, orally, every 24 hours plus BSC on Days 1 to 28 (28 day cycles).

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

Published Research Related to This Trial

Abemaciclib is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

In a phase 1b study involving 50 patients with advanced non-small cell lung cancer (NSCLC), the combination of abemaciclib and pembrolizumab showed significant toxicity, with 80% of patients in cohort A and 76% in cohort B experiencing severe treatment-emergent adverse events.

Despite some antitumor activity, including a disease control rate of 56% in cohort A and 64% in cohort B, the overall risk-benefit profile of this combination therapy does not support further investigation in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. Pujol, JL., Vansteenkiste, J., Paz-Ares Rodríguez, L., et al.[2022]

In a Phase 1b study involving 67 women with hormone receptor positive (HR+) and HER2 negative metastatic breast cancer, abemaciclib combined with endocrine therapies showed a median progression-free survival of 25.4 months and an objective response rate of 38.9%.

The treatment was generally well-tolerated, with manageable side effects such as diarrhea and fatigue, and no significant impact on the pharmacokinetics of the endocrine therapies used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study. Tolaney, SM., Beeram, M., Beck, JT., et al.[2022]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

In phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

Abemaciclib has demonstrated promising clinical activity in patients with relapsed mesothelioma that is deficient in the p16ink4A protein, suggesting it may be an effective treatment option for this specific cancer type.

The findings indicate a potential new therapeutic avenue for mesothelioma patients, particularly those whose tumors lack the p16ink4A protein, which is often associated with tumor suppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CDK4/6 Inhibition Shows Clinical Activity in p16ink4A-Deficient Mesothelioma. [2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02079636

A Study of Abemaciclib (LY2835219) in Combination With ... The main purpose of this study is to evaluate the safety and tolerability of abemaciclib in combination with another anti-cancer drug in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02779751

NCT02779751 | A Study of Abemaciclib (LY2835219) in ... The main purpose of this study is to evaluate the safety and efficacy of abemaciclib in combination with pembrolizumab in participants with advanced ...

3. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(15)00190-4/fulltext

A Randomized Phase III Study of Abemaciclib With Best ... JUNIPER is a randomized study of abemaciclib (200 mg orally every 12 hours) with best supportive care (BSC) versus erlotinib (150 mg orally every 24 hours) with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11994929/

Survival benefit from abemaciclib in non–small cell lung ... In the phase III JUNIPER trial, abemaciclib did not demonstrate an overall survival (OS) benefit in patients with NSCLC who harbored a KRAS ...

5. trials.lilly.com trials.lilly.com/en-US/trial/115042

A Study of Abemaciclib (LY2835219) in Participants With Non ... The main purpose of this study is to evaluate the safety and efficacy of abemaciclib in combination with pembrolizumab in participants with advanced ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02079636

A Study of Abemaciclib (LY2835219) in Combination With ... The main purpose of this study is to evaluate the safety and tolerability of abemaciclib in combination with another anti-cancer drug in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02152631

NCT02152631 | A Study of Abemaciclib (LY2835219) in ... The main purpose of this study is to evaluate how safe and effective the study drug known as abemaciclib is in participants with lung cancer.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30082474/

Abemaciclib in Combination with Single-Agent Options ... Abemaciclib demonstrated an acceptable safety profile when dosed on a continuous twice-daily schedule in combination with pemetrexed, gemcitabine, or ...

9. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT02779751

Abemaciclib (LY2835219) in Participants With Non-Small ... The main purpose of this study is to evaluate the safety and efficacy of abemaciclib in combination with pembrolizumab in participants with advanced non-small ...