Abemaciclib for Small Cell Lung Cancer

Overseen By Afshin Dowlati, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Antiretrovirals, Investigational agents

Disqualifiers: Pregnancy, Severe dyspnea, Cardiac arrhythmia, others

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

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: 4

Duration: 4 weeks per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medicine called Abemaciclib, a CDK4/6 inhibitor, to determine if it can shrink tumors in people with specific types of lung cancer. The trial evaluates the effectiveness and safety of Abemaciclib for small cell lung cancer and related cancers, especially when the cancer has not responded to or has returned after chemotherapy. Suitable candidates for this trial include those whose lung cancer has recurred or not improved after chemotherapy and who can swallow pills. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational agents or combination antiretroviral therapy for HIV, you would not be eligible to participate.

Is there any evidence suggesting that Abemaciclib is likely to be safe for humans?

Research shows that Abemaciclib, a type of medication, has been tested for safety in different cancers. Studies have found that patients usually tolerate Abemaciclib well when taken twice a day with other cancer treatments. Common side effects include diarrhea, tiredness, and nausea, but these can often be managed. Serious side effects occur less frequently.

In trials with patients who have breast cancer and non-small cell lung cancer, the treatment proved safe. This suggests that Abemaciclib might also be tolerated in small cell lung cancer (SCLC) and similar conditions. However, since this trial focuses on SCLC and other high-grade neuroendocrine cancers, participants might experience different side effects, so regular monitoring remains important. ^{1 2 3 4 5}

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

Abemaciclib is unique because it targets specific proteins called CDK4 and CDK6, which are involved in cell division. Unlike standard treatments for small cell lung cancer, such as chemotherapy and radiation, which broadly attack rapidly dividing cells, Abemaciclib offers a more targeted approach. This specificity might result in fewer side effects and potentially better outcomes. Researchers are excited because it represents a shift towards precision medicine, which could lead to more effective and personalized treatment options for patients.

What evidence suggests that Abemaciclib might be an effective treatment for small cell lung cancer?

Research has shown that Abemaciclib, a type of medication, has potential in treating certain cancers. Studies found that Abemaciclib effectively stops cancer cells from growing, including in some lung cancers. It notably shrinks tumors in patients with advanced cancer. Some trials found that Abemaciclib can outperform standard treatments like docetaxel, particularly in stage IV lung cancers. This trial will evaluate Abemaciclib as an option for patients with small cell lung cancer that hasn't responded to other treatments. ^{1 5 6 7 8}

Who Is on the Research Team?

Afshin Dowlati, MD

Principal Investigator

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain types of lung cancer that haven't improved after chemotherapy. They should have a specific gene type (Rb wild-type), measurable disease, and be able to take pills orally. Participants need good organ function and can't join if they're pregnant, breastfeeding, or have serious medical conditions like severe lung disease or uncontrolled infections.

Inclusion Criteria

My cancer is confirmed to be retinoblastoma wild type.

Subjects must have the ability to understand and the willingness to sign a written informed consent document.

You must have a specific amount of measurable disease according to certain medical guidelines.

Exclusion Criteria

I am not HIV-positive or not on antiretroviral therapy.

My side effects from previous treatments are mild, except for hair loss or nerve issues.

I do not have severe lung problems, major stomach surgery, Crohn's, ulcerative colitis, or chronic severe diarrhea.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Abemaciclib (200 mg) orally every 12 hours on days 1 to 28 of a 28-day cycle

4 weeks per cycle

Evaluations after 4 weeks and then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 90 days from end of treatment

Long-term follow-up

Overall survival and progression-free survival are assessed

Up to 10 years from start of study

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib

Trial Overview

The study tests Abemaciclib's effectiveness in shrinking tumors in patients with small cell lung cancer and related cancers that are resistant to chemo. It also examines the safety of this drug in those who've had no response to initial treatments or whose cancer returned post-chemo.

How Is the Trial Designed?

Group I: Abemaciclib Experimental Treatment 1 Intervention

* Subjects will receive Abemaciclib (200 mg), orally every 12 hours on days 1 to 28 of a 28-day cycle for a total of 56 doses per cycle. * Subjects will be evaluated after 4 weeks (1st cycle) and then every 8 weeks (2 cycles) with radiographic imaging to assess response to treatment.

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?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

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]

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 study involving 900 patients treated with abemaciclib for advanced breast cancer, patient-reported outcomes (PROs) such as physical function and pain were found to be significant predictors of progression-free survival (PFS), indicating their importance in treatment outcomes.

Patients with low physical function experienced a reduced benefit from abemaciclib compared to those with intermediate or high physical function, highlighting the need to consider PROs as independent prognostic markers in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes Predict Progression-Free Survival of Patients with Advanced Breast Cancer Treated with Abemaciclib. Badaoui, S., Kichenadasse, G., Rowland, A., 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]

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