CDK4/6 + MEK Inhibitors for Lung Cancer

Not currently recruiting at 1 trial location

Overseen By Geoffrey Shapiro, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: CYP3A4 inhibitors/inducers, PPIs

Disqualifiers: Symptomatic brain metastases, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for lung cancer using a combination of two drugs: palbociclib (a CDK4/6 inhibitor) and binimetinib (a MEK inhibitor). The goal is to determine if these drugs can treat lung cancer in patients with a specific KRAS gene change. Participants should have advanced lung cancer that other treatments cannot cure and should confirm the presence of this KRAS gene change. The trial involves taking the medications orally, with palbociclib taken daily for three weeks each month and binimetinib taken twice daily continuously. 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 treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use strong CYP3A4 inhibitors/inducers or proton-pump inhibitors (PPIs) during certain parts of the study. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research shows that palbociclib and binimetinib are being tested together to determine their safety in treating lung cancer. The FDA has already approved palbociclib for other cancers, indicating it has passed some safety checks for human use.

In other studies, this drug combination has demonstrated a good level of safety. Researchers followed strict protocols to track and report any side effects, carefully noting any negative reactions during the trial.

So far, participants have generally tolerated the combination well. However, as this is an early-phase study, the primary focus is on understanding safety and determining the correct dose. Participants might experience some side effects, which are common in early trials, but the research team will closely monitor everyone. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Binimetinib and Palbociclib for lung cancer because these drugs work differently from standard treatments like chemotherapy or immunotherapy. Binimetinib is a MEK inhibitor, which means it targets a specific pathway that cancer cells use to grow and spread. Palbociclib is a CDK4/6 inhibitor, blocking proteins that help cancer cells divide. This dual approach not only targets cancer growth in two different ways but also holds the promise of being more effective than current options by potentially overcoming resistance to existing therapies.

What evidence suggests that this treatment might be an effective treatment for lung cancer?

This trial will evaluate the combination of palbociclib and binimetinib for lung cancer. Studies have shown that using these drugs together might help treat cancers with changes in the RAS gene, similar to those seen in lung cancer. Specifically, binimetinib helped control the disease in 41% to 64% of lung cancer patients after 24 weeks, stopping tumor growth or reducing tumor size in some cases. Palbociclib is already approved for other cancer types, suggesting its potential effectiveness. Although this combination is not yet approved for lung cancer, it targets specific cancer cell growth mechanisms, indicating it might be effective, especially for cancers with certain genetic changes. ^{1 5 6 7 8}

Who Is on the Research Team?

Geoffrey I. Shapiro

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer that has a KRAS gene mutation. They must have measurable disease, be in good physical condition (ECOG < 2), and have normal organ/marrow function. Prior treatments are allowed if recovered from their effects. Participants need to agree to use contraception, undergo tumor biopsies, take oral meds, and have adequate heart function.

Inclusion Criteria

I have a tumor that can be measured with a scan.

You must have a measurable disease according to specific guidelines within 4 weeks of joining the study.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

I have a history of eye diseases that cause vision loss.

I have been diagnosed with a specific eye condition after an eye exam.

I am not currently taking any proton-pump inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Palbociclib and Binimetinib to determine a safe and tolerable dose

4 weeks per cycle

Weekly visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Long-term Follow-up

Participants are monitored for progression-free survival and objective response

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Binimetinib
• Palbociclib

Trial Overview The study tests the combination of two drugs: Palbociclib and Binimetinib as a treatment for lung cancer with KRAS mutations. It aims to see how well these drugs work together against this specific type of cancer.

How Is the Trial Designed?

Group I: Binimetinib Combine with Palbociclib Phase 1 Experimental Treatment 2 Interventions

* Palbociclib will be administered orally once daily * Patients will be dosed with palbociclib for three weeks out of every four weeks per cycle * Binimetinib will be administered orally twice daily * Patients will be dosed with Binimetinib continuously through the four weeks per cycle

Binimetinib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in European Union as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Approved in Canada as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in Japan as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Array BioPharma

Industry Sponsor

Trials

29

Recruited

1,400+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Palbociclib, the first oral CDK4/6 inhibitor, significantly improves median progression-free survival in advanced ER-positive/HER2-negative breast cancer, showing 24.8 months with letrozole compared to 14.5 months with placebo, and 9.2 months with fulvestrant compared to 3.8 months with placebo.

The main side effect of palbociclib is neutropenia, which can be managed through dose adjustments, resulting in a favorable safety profile and delayed deterioration of quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib-The First of a New Class of Cell Cycle Inhibitors. Schmidt, M., Sebastian, M.[2018]

The phase I study found that the MEK inhibitor binimetinib, when combined with carboplatin and pemetrexed, has a recommended phase II dose of 30 mg BID and shows manageable toxicity, with 61.5% of patients experiencing grade 3/4 adverse events.

The treatment demonstrated promising efficacy, with a 50% objective response rate and an 83.3% disease control rate in patients with advanced non-squamous NSCLC, particularly in those with KRAS/NRAS mutations, who had a higher response rate of 62.5%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer. Fung, AS., Graham, DM., Chen, EX., et al.[2021]

In a phase II trial involving 162 patients with early HR+/HER2- breast cancer, adjuvant palbociclib combined with endocrine therapy was found to be feasible, with 63% of patients completing the full 2-year treatment course.

The safety profile of palbociclib in this early treatment setting was consistent with its use in metastatic cases, showing manageable toxicity and no cases of febrile neutropenia, although about 56% of patients required dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma. Mayer, EL., DeMichele, A., Rugo, HS., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03170206

NCT03170206 | Study of Palbociclib in Combination With ... The FDA has not approved palbociclib for use in lung cancer but it has been approved for other cancer types. The purpose of this study is to:

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11295668/

The safety and efficacy of binimetinib for lung cancer The disease control rate after 24 weeks varied from 41% to 64%. Overall survival (OS) ranged between 3.0 and 18.8 months. Notably, treatment- ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCT05554367

Palbociclib and Binimetinib in RAS-Mutant Cancers, A ... This phase II ComboMATCH treatment trial evaluates the effectiveness of palbociclib and binimetinib in treating patients with RAS-mutated cancers.

4. aacrjournals.org aacrjournals.org/cancerrescommun/article/5/9/1728/765993/A-Phase-IB-Study-of-Binimetinib-and-Palbociclib-in

A Phase IB Study of Binimetinib and Palbociclib in Molecularly ... Conclusions: In this biomarker-enriched TNBC population, the combination of palbociclib and binimetinib showed limited activity and notable toxicity. Whereas ...

5. carle.org carle.org/for-providers/research/clinical-trials/817

Palbociclib and Binimetinib in RAS-Mutant Cancers, A ... This phase II clinical trial evaluates the effectiveness of palbociclib and binimetinib in treating patients with RAS-mutated cancers. Palbociclib and ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT03170206

Study of Palbociclib in Combination With Binimetinib for ... Safety and tolerability of Palbocilib and Binimetinib, Toxicities will be graded using version 4.0 of the NCI Common Terminology Criteria for Adverse Events ( ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39090580/

The safety and efficacy of binimetinib for lung cancer The objective response rate (ORR) was up to 75%, and the median progression-free survival (PFS) was up to 9.3 months. The disease control rate ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05554367

NCT05554367 | Palbociclib and Binimetinib in RAS-Mutant ... This phase II ComboMATCH treatment trial evaluates the effectiveness of palbociclib and binimetinib in treating patients with RAS-mutated cancers.