Palbociclib + Binimetinib for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+280 other locations
Overseen ByGeoffrey I Shapiro
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Strong CYP3A4 inhibitors, Strong CYP3A4 inducers, P-gp inhibitors, P-gp inducers
Disqualifiers: Pregnancy, Interstitial lung disease, Bowel perforation, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II ComboMATCH treatment trial evaluates the effectiveness of palbociclib and binimetinib in treating patients with RAS-mutated cancers. Palbociclib and binimetinib are both in a class of medications called kinase inhibitors. They work by blocking the action of abnormal proteins that signals cancer cells to multiply. This trial may help researchers understand if giving the combination of palbociclib and binimetinib can help improve the amount of time before the cancer grows in patients with patients with low grade serous ovarian cancer who have certain changes in the tumor DNA. This trial may also help researchers understand if giving the combination of palbociclib and binimetinib can help improve outcomes among patients with low grade serous ovarian cancer who have previously received a MEK inhibitor. For patients with other tumors, with the exception of lung cancer, colon cancer, melanoma and low grade serous ovarian cancers, this trial may help researchers understand if giving the combination of palbociclib and binimetinib can improve the clinical outcome of survival without progression in patients who have certain changes in their tumor's DNA.
Will I have to stop taking my current medications?
The trial requires that you stop taking any cancer-directed therapy at least 28 days before joining, except for hormonal therapy, which can be taken up to 14 days before. Additionally, you must stop taking strong CYP3A4 inhibitors or inducers and P-glycoprotein inhibitors or inducers 14 days before starting the trial.
What data supports the effectiveness of the drug combination of Palbociclib and Binimetinib for pancreatic cancer?
Research shows that binimetinib, a MEK inhibitor, has shown effectiveness in treating certain cancers like melanoma and colorectal cancer, especially when combined with other targeted therapies. Additionally, a case report indicated a positive tumor response in pancreatic cancer when a similar MEK inhibitor was used with a BRAF inhibitor.
12345Is the combination of Palbociclib and Binimetinib safe for humans?
Binimetinib has been studied for safety in humans, particularly in patients with advanced solid tumors, and its maximum tolerated dose was determined in a phase 1 study. However, specific safety data for the combination of Palbociclib and Binimetinib in humans is not provided in the available research.
23678What makes the drug combination of Palbociclib and Binimetinib unique for treating pancreatic cancer?
The combination of Palbociclib and Binimetinib is unique because it targets specific pathways involved in cancer cell growth, with Palbociclib inhibiting cell cycle progression and Binimetinib blocking MEK enzymes, which are part of a signaling pathway often active in cancers. This dual approach may offer a novel way to tackle pancreatic cancer compared to standard treatments.
123910Eligibility Criteria
This trial is for patients with RAS-mutated cancers, such as low grade serous ovarian cancer and pancreatic cancer, who have no curable treatment options. Participants must have measurable disease, be able to undergo a biopsy, and not have had prior MEK inhibitor or CDK4/6 inhibitor therapy (with exceptions for certain mutations). They should also meet all ComboMATCH Registration Protocol criteria.Inclusion Criteria
My cancer cannot be cured with surgery or other common treatments.
I have not taken MEK inhibitor or CDK4/6 inhibitor drugs before.
I meet all requirements of the ComboMATCH study and have submitted my genetic testing data.
My cancer has specific genetic changes in KRAS, NRAS, HRAS, or BRAF.
I have low grade serous ovarian cancer with a specific genetic mutation.
Participant Groups
The effectiveness of combining two kinase inhibitors, palbociclib and binimetinib, is being tested in this phase II trial. The study aims to see if this drug combo can delay cancer growth in patients with specific tumor DNA changes and improve survival without progression in various cancers excluding lung, colon cancer, melanoma.
2Treatment groups
Experimental Treatment
Group I: Monotherapy Cohort 1 (binimetinib)Experimental Treatment6 Interventions
Patients receive binimetinib PO BID daily, in the absence of disease progression or unacceptable toxicity, for up to 3 years. Patients who experience disease progression may elect to migrate to the combination cohort. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
Group II: Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)Experimental Treatment7 Interventions
Patients receive palbociclib PO QD on days 1-21 and binimetinib PO BID on days 1-28 of each cycle. throughout the trial. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity for up to 3 years. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.
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
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Northwestern Medicine Grayslake Outpatient CenterGrayslake, IL
Inova Schar Cancer InstituteFairfax, VA
Dana-Farber Cancer InstituteBoston, MA
University of Chicago Medicine-Orland ParkOrland Park, IL
More Trial Locations
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Who is running the clinical trial?
National Cancer Institute (NCI)Lead Sponsor
References
Avelumab or talazoparib in combination with binimetinib in metastatic pancreatic ductal adenocarcinoma: dose-finding results from phase Ib of the JAVELIN PARP MEKi trial. [2023]Combinations of avelumab [anti-programmed death-ligand 1 (anti-PD-L1)] or talazoparib [poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor] with binimetinib (MEK inhibitor) were expected to result in additive or synergistic antitumor activity relative to each drug administered alone. Here, we report phase Ib results from JAVELIN PARP MEKi, which investigated avelumab or talazoparib combined with binimetinib in metastatic pancreatic ductal adenocarcinoma (mPDAC).
The discovery and development of binimetinib for the treatment of melanoma. [2021]Label="INTRODUCTION">Binimetinib is an uncompetitive, small-molecule inhibitor of selective mitogen-activated protein kinase (MEK1/2) and was recently approved in 2018 in combination with encorafenib for the treatment of metastatic melanomas. Preclinical and clinical trial data on the drug demonstrate its potent efficacy in cancers, especially melanomas with BRAF and NRAS mutations.
A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. [2022]Binimetinib (MEK162; ARRY-438162) is a potent and selective oral MEK 1/2 inhibitor. This phase 1 study determined the maximum tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic profiles, and preliminary anti-tumour activity of binimetinib in patients with advanced solid tumours, with expansion cohorts of patients with biliary cancer or KRAS- or BRAF-mutant colorectal cancer.
Molecular Targeting of a BRAF Mutation in Pancreatic Ductal Adenocarcinoma: Case Report and Literature Review. [2021]Current standard-of-care treatment for advanced pancreatic ductal adenocarcinoma is mainly based on conventional cytotoxic chemotherapy. Until recently, no randomized clinical trials had shown any clinically meaningful outcome benefit from targeted therapy in this indication. This is in contrast to many other tumor types. The majority of pancreatic tumors are driven by KRAS mutations, which are generally not amenable to targeted therapy. Driving mutations in the BRAF oncogene have proven to be an interesting molecular target in the management of advanced melanoma and colorectal adenocarcinoma and can be found in 3% of patients with advanced pancreatic ductal adenocarcinoma. Here, we report objective tumor response to treatment with the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib in a patient with poorly differentiated, V600E mutant, advanced pancreatic ductal adenocarcinoma.
Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. [2023]This multicenter, open-label, phase Ib study investigated the safety and efficacy of binimetinib (MEK inhibitor) in combination with buparlisib (phosphatidylinositol 3-kinase [PI3K] inhibitor) in patients with advanced solid tumors with RAS/RAF alterations.
Pancreatic adverse events in patients treated with immune checkpoint inhibitors. [2023]The inhibition of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) has been a target for multiple drugs to enhance the T-cell antitumor activity. However, these immune checkpoint inhibitors (ICIs) come with a panel of immune-related adverse events (irAEs) that include mainly endocrine, skin, and gastrointestinal effects. We report seven cases of pancreatic irAEs in patients treated with ICIs at our institute.
Pancreatic Adverse Events Associated With Immune Checkpoint Inhibitors: A Large-Scale Pharmacovigilance Analysis. [2022]Backgrounds: Immune checkpoint inhibitors (ICIs) are considered cornerstones of oncology treatment with durable anti-tumor efficacy, but the increasing use of ICIs is associated with the risk of developing immune-related adverse events (irAEs). Although ICI-associated pancreatic adverse events (AEs) have been reported in patients treated with ICIs, the clinical features and spectrum of pancreatic AEs are still not well-defined. Therefore, this study aimed to identify the association between pancreatic AEs and ICIs treatments and to characterize the main features of ICI-related pancreatic injury (ICIPI) based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database.
A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. [2021]Label="PURPOSE">This open-label, dose-finding phase Ib/II study reports the safety and activity of the first combination use with BRAF inhibitor (BRAFi) encorafenib plus MEK inhibitor (MEKi) binimetinib in patients with BRAF V600E-mutant solid tumors.
A Multicenter, Open-Label Phase II Clinical Trial of Combined MEK plus EGFR Inhibition for Chemotherapy-Refractory Advanced Pancreatic Adenocarcinoma. [2021]On the basis of preclinical evidence of synergistic activity between MEK and EGFR inhibitors in pancreatic ductal adenocarcinoma (PDAC), we evaluated the safety and efficacy of selumetinib, a MEK1/2 inhibitor, plus erlotinib in patients with previously treated advanced PDAC.
Encorafenib and Binimetinib: First Global Approvals. [2019]Encorafenib (Braftovi™), a BRAF inhibitor, and binimetinib (Mektovi®), a MEK inhibitor, are two orally bioavailable drugs developed by Array BioPharma. In June 2018 they each received their first global approval, in the USA, for use in combination, for patients with unresectable or metastatic melanoma with a BRAFV600E or -V600K mutation as detected by an FDA-approved test. Registration applications for encorafenib and binimetinib for use in combination in the treatment of BRAF-mutation-positive advanced melanoma have also been submitted in the EU, Australia, Switzerland and Japan, with the EMA Committee for Medicinal Products for Human Use adopting a positive opinion in July 2018 towards granting the drugs marketing authorizations in the EU. Encorafenib plus binimetinib combination therapy is also in ongoing phase III clinical development in the treatment of metastatic colorectal cancer. This article summarizes the milestones in the development of encorafenib and binimetinib leading to these first approvals for the treatment of BRAFV600E or -V600K-mutation-positive unresectable or metastatic melanoma.