Abemaciclib Combo for Lung Cancer or alternatively, if focusing on breast cancer: Abemaciclib Combo for Breast Cancer

Not currently recruiting at 37 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eli Lilly and Company

Must be taking: GnRH agonists

Must not be taking: Systemic steroids, Autoimmune agents

Disqualifiers: Cardiac history, CNS metastasis, 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: 21-day cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for advanced lung and breast cancers. Researchers aim to determine the safety and effectiveness of using abemaciclib (a targeted cancer therapy) and pembrolizumab (an immunotherapy drug) together. Participants with advanced non-small cell lung cancer or specific types of breast cancer (HR+ and HER2-) may qualify, especially if they have undergone certain prior treatments. The goal is to discover better ways to treat these cancers and improve patient outcomes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop all previous cancer treatments and recover from their effects before starting the study. If you are in Part D, you must not have received endocrine therapy or chemotherapy for metastatic breast cancer, but prior treatment for localized disease is allowed.

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

Research has shown that using abemaciclib with pembrolizumab for advanced non-small cell lung cancer (NSCLC) raises some safety concerns. Previous studies found that this combination caused more side effects than when each drug was used alone. These side effects can range from mild to serious, but specific details and their frequency were not provided.

For hormone receptor positive (HR+), human epidermal growth factor receptor negative (HER2-) breast cancer, studies indicate that the combination of abemaciclib and pembrolizumab is generally well-tolerated. Some side effects have been noted, but they are usually manageable. Adding anastrozole to this mix also showed good results without causing significant additional safety issues.

These combination treatments are in the early testing phase (Phase 1), which involves careful monitoring for safety. This phase is crucial to understanding how the body reacts and ensuring any side effects can be managed. While some risks exist, the trials are designed to keep participants safe and informed. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Abemaciclib and Pembrolizumab for both lung and breast cancer because it offers a novel approach compared to standard treatments. Unlike typical therapies for non-small cell lung cancer (NSCLC) and HR+, HER2- breast cancer, which often involve chemotherapy or hormone therapy, Abemaciclib works by specifically inhibiting certain proteins that promote cancer cell growth. Pembrolizumab, an immunotherapy, enhances the ability of the immune system to target and kill cancer cells. This dual-action approach not only targets cancer cells directly but also boosts the body's natural defenses, potentially leading to improved outcomes and offering hope for patients with advanced or resistant cancer types.

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

In this trial, participants with non-small cell lung cancer (NSCLC) will receive a combination of abemaciclib and pembrolizumab. Previous studies have shown that this combination can shrink or control tumor growth in NSCLC. Abemaciclib is already approved as a standalone treatment for hormone receptor-positive (HR+), HER2-negative breast cancer and has been shown to extend patient survival when used with other therapies. In this trial, some participants will receive abemaciclib combined with pembrolizumab, which has shown positive effects in earlier studies. Additionally, for advanced-stage HR+ breast cancer, the combination of abemaciclib, pembrolizumab, and anastrozole has further improved survival times. Overall, these combination treatments show promise in controlling cancer growth and extending patient survival. ^{1 2 3 4 5}

Who Is on the Research Team?

Call 1-877-CTILLY (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 advanced non-small cell lung cancer or hormone receptor positive, HER2- breast cancer. Participants must have a good performance status and may have had certain prior treatments depending on the study part they're in. They should not have used specific immune therapies before, no recent live vaccines, and must be free of certain heart and lung conditions.

Inclusion Criteria

I am fully active or can carry out light work.

You have a detectable tumor according to specific guidelines.

My cancer is advanced and falls into one of the specified categories.

Exclusion Criteria

I have had interstitial lung disease or pneumonitis.

I have an autoimmune disease or have been on steroids or immune drugs for the past 2 years.

I have not had a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive abemaciclib orally every 12 hours and pembrolizumab intravenously on day 1 of each 21-day cycle. Anastrozole is also given orally for certain breast cancer participants.

21-day cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Pembrolizumab

Trial Overview The trial tests abemaciclib combined with pembrolizumab's safety and effectiveness against advanced NSCLC or HR+, HER2- breast cancer. It aims to see how well this combination works for patients who meet specific previous treatment criteria.

How Is the Trial Designed?

Group I: NSCLC Squamous Experimental Treatment 2 Interventions

Abemaciclib given orally Q12H on days 1 to 21 of each 21 day cycle in combination with pembrolizumab given IV on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Group II: NSCLC KRAS mt, PD-L1+ Experimental Treatment 2 Interventions

Abemaciclib given orally every 12 hours (Q12H) on days 1 to 21 of each 21 day cycle in combination with pembrolizumab given intravenously (IV) on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Group III: HR+, HER2- Metastatic Breast Cancer Experimental Treatment 2 Interventions

Abemaciclib given orally Q12H on days 1 to 21 of each 21 day cycle in combination with pembrolizumab given IV on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Group IV: HR+, HER2- Locally Advanced or Metastatic Breast Cancer Experimental Treatment 3 Interventions

Abemaciclib given orally Q12H on days 1 to 21 of each 21 day cycle in combination with pembrolizumab given IV on day 1 of each 21 day cycle and anastrozole given orally Q24H on days 1 to 21 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[2023]

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]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

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]

Citations

1. nature.com nature.com/articles/s41523-022-00482-2

Abemaciclib in combination with pembrolizumab for HR+, ... Pembrolizumab has demonstrated robust antitumor activity and is FDA-approved in combination with chemotherapy for the treatment of PD-L1- ...

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. asco.org asco.org/abstracts-presentations/ABSTRACT213571

metastatic breast cancer administered abemaciclib plus ... Background: Abemaciclib is a selective inhibitor of CDK4 & 6 approved to treat HR+, HER2- metastatic breast cancer (MBC) patients (pts) as monotherapy and ...

4. onclive.com onclive.com/view/abemaciclib-plus-endocrine-therapy-provides-os-benefit-in-hr-her2-negative-breast-cancer

Abemaciclib Plus Endocrine Therapy Provides OS Benefit ... Abemaciclib plus endocrine therapy reduced death risk by 15.8% in high-risk early breast cancer patients compared to endocrine therapy alone.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10730497/

Metastatic Breast Cancer Receiving Abemaciclib in ... Patients with metastatic breast cancer (mBC) have a 5-year survival of < 30% [1]. Hormone receptor-positive (HR+)/human epidermal growth factor ...