Osimertinib + Abemaciclib for Non-Small Cell Lung Cancer after Osimertinib Resistance

Overseen By Sarah Moore

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must be taking: Osimertinib

Must not be taking: CYP3A4 inducers

Disqualifiers: Cardiovascular disease, Hepatitis, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining two drugs, Osimertinib and Abemaciclib (a CDK4/6 inhibitor), can effectively treat non-small cell lung cancer (NSCLC) that has not responded well to Osimertinib alone. Researchers hope this combination might be more effective for individuals whose cancer has a specific genetic mutation and has spread or returned after treatment. Ideal participants are those diagnosed with advanced NSCLC that worsened after using Osimertinib. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have taken chemotherapy or other investigational agents within three weeks before starting the study treatment, and you should not use medications or supplements that are major inducers of CYP3A4.

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

Research shows that combining Osimertinib and Abemaciclib may help treat non-small cell lung cancer (NSCLC). Patients using Osimertinib, alone or with chemotherapy, have generally found it safe and beneficial for survival, with most not experiencing severe or unexpected side effects.

When combined with Osimertinib, Abemaciclib has slowed cancer cell growth and delayed resistance to treatment. This suggests it could be a promising addition without major safety issues.

Overall, both drugs are usually well-tolerated, and their combination has shown positive results. However, as this is a Phase 2 trial, researchers are still working to confirm these safety findings in more people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Osimertinib and Abemaciclib for treating non-small cell lung cancer because this duo targets the cancer in a novel way. Osimertinib is already known for blocking EGFR mutations, a common driver in lung cancer, but cancer cells can become resistant over time. Abemaciclib adds a new twist by inhibiting CDK4/6, which are proteins that help cancer cells divide and grow. This combination aims to tackle resistance and potentially improve outcomes where other treatments, like chemotherapy or other targeted therapies, may not be as effective.

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

Research shows that combining Osimertinib with Abemaciclib can slow or halt the growth of non-small cell lung cancer. This trial will evaluate the combination of Osimertinib, also known as Tagrisso, and Abemaciclib in a single treatment arm. Studies have shown that Osimertinib effectively extends the lives of patients with a specific type of lung cancer. Abemaciclib blocks certain proteins in cancer cells, preventing their growth. Together, these drugs offer a promising option for patients whose cancer no longer responds to standard treatments. ^{3 5 6 7 8}

Who Is on the Research Team?

Hatim Husain, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

Adults over 18 with Stage IV, recurrent or metastatic non-small cell lung cancer that has an EGFR mutation and have shown resistance to osimertinib treatment. They must be able to swallow pills, not have serious heart conditions or uncontrolled illnesses, and agree to use contraception. Those with certain prior treatments or health issues like interstitial lung disease are excluded.

Inclusion Criteria

At least one measurable lesion according to RECIST version 1.1

Histologically or cytologically confirmed NSCLC-lung adenocarcinoma histology

ECOG performance status ≤1

Exclusion Criteria

You have a lung disease called interstitial lung disease, except if it was caused by radiation treatment and is not currently being treated or causing symptoms.

You have certain health conditions like unstable angina, congestive heart failure, or gastrointestinal diseases that may affect how well you can take the study medication. You also have mental health issues or other personal situations that may make it difficult for you to participate or follow the study requirements.

Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of osimertinib (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea, and malabsorption)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Osimertinib 80 mg QD and Abemaciclib 150 mg BID

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Osimertinib

Trial Overview

The trial is testing the combination of Osimertinib and Abemaciclib in patients whose non-small cell lung cancer has become resistant to Osimertinib alone. It aims to see if this combo can overcome resistance and improve outcomes.

How Is the Trial Designed?

Group I: Single Arm, POC Experimental Treatment 2 Interventions

Single arm, POC Safety and Efficacy Osimertinib 80 mg QD Abemaciclib 150mg BID

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?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Eli Lilly and Company

Industry 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

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

Osimertinib (AZD9291) is effective in prolonging survival for non-small cell lung cancer patients with EGFR mutations, but resistance to the drug is a common issue, prompting the need to explore resistance mechanisms.

In this study, AZD9291-resistant NSCLC cell lines were established, revealing significant changes in circular RNA (circRNA) expression profiles, which may contribute to drug resistance and could serve as potential targets for future gene therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines. Chen, T., Luo, J., Gu, Y., et al.[2022]

In a study of 240 advanced non-small-cell lung cancer (NSCLC) patients with acquired resistance to EGFR TKIs, 52.9% had the T790M mutation after rebiopsy, highlighting the mutation's prevalence in treatment resistance.

Patients with the T790M mutation who had previously used osimertinib experienced significantly longer post-progression survival (42.6 months) compared to those without osimertinib (18.0 months) or without the mutation (18.8 months), suggesting osimertinib's effectiveness as a standard treatment for T790M-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. Chiang, CL., Huang, HC., Shen, CI., et al.[2022]

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