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

29 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to: * Test how well the study medicine Abemaciclib, a CDK4/6 inhibitor, works to shrink lung cancer tumors in the body. * Test the safety of Abemaciclib when given to participants with small cell lung cancer (SCLC), large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung. Specifically, this study is looking at SCLC, large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung that have not responded to treatment (refractory) or come back after treatment with chemotherapy (relapsed) as the study medication has been shown to be effective any time the disease relapses not just in the first few months.

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.

How is the drug Abemaciclib unique for treating small cell lung cancer?

Abemaciclib is unique because it is a selective inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), which are proteins that help control cell division, and it is typically used in combination with other therapies to enhance its anticancer effects. This mechanism of action is different from many traditional chemotherapy drugs, which often target rapidly dividing cells more broadly. ^{1 2 3 4 5}

Research Team

Afshin Dowlati, MD

Principal Investigator

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

Eligibility Criteria

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.

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

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes Predict Progression-Free Survival of Patients with Advanced Breast Cancer Treated with Abemaciclib. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

5. Switzerland 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. [2022]