Palbociclib and Binimetinib in RAS-Mutant Cancers, A ComboMATCH Treatment Trial

Running, not enrolling · Phase 2

Conditions studied: Exocrine Pancreas Carcinoma, Malignant Solid Neoplasm, Ovarian Low Grade Serous Adenocarcinoma, Stage IV Ovarian Cancer AJCC v8, Stage IV Pancreatic Cancer AJCC v8

In brief

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.

Key facts

Study ID

NCT05554367

Run by

National Cancer Institute (NCI)

People needed

199

Starts

2023-12-13

Expected to finish

2026-08-26

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-A3 based on the presence of an actionable mutation as defined in EAY191.
• GENERAL ComboMATCH EAY191 REGISTRATION INCLUSION CRITERIA:
• Patients must be enrolled on the EAY191 registration study and be assigned to this protocol by EAY191
• Patients must have KRAS/NRAS/HRAS or RAF mutations or rare RAF fusions as determined by the ComboMATCH screening assessment
• Patients with low grade serous ovarian cancer who have progressed on a prior MEK inhibitor are not required to have a KRAS/NRAS/HRAS or BRAF alteration
• Patients must not have a BRAF V600E alteration as determined by the ComboMATCH screening assessment
• Patients with a tumor harboring KRAS G12C mutation will be eligible either after they have received a G12C inhibitor or can be enrolled if they do not meet eligibility for a G12C inhibitor. However, patients with tumors harboring KRAS G12C mutation will be prioritized for a G12C inhibitor-based substudy if eligible
• Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to registration
• Please note the current actionable marker of interest (aMOI)/actionable alteration list for this treatment trial can be found on the Cancer Trials Support Unit (CTSU) website
• EAY191-A3 IELIGIBILITY CRITERIA:
• Histologically confirmed cancer for each cohort for which curable treatment modalities are not an option. Rare BRAF fusions and non-BRAF V600E aMOIs are acceptable. RB1 mutations or two copy RB1 deletions are excluded
• Tumor tissue must be available:
• Adequate archival tumor specimen (obtained within 12 months of EAY191 registration which has not had a Response Evaluation Criteria in Solid Tumors (RECIST) response, complete response (CR) or partial response (PR), to any intervening therapy after collection of the tissue) must be available with formalin-fixed paraffin-embedded tumor tissue (blocks or slides) OR
• Consent to a new tumor tissue biopsy which is not a representative target lesion. This lesion must be amenable to a minimal risk image-guided or direct vision biopsy A new biopsy is preferred but is not required for enrollment in EAY191-A3 if sufficient archival tissue is available as described above
• Measurable disease per RECIST 1.1. Of note, in the case when a baseline biopsy is done after scans are obtained, a lesion separate from one that is biopsied needs to be measurable per RECIST 1.1. All radiologic studies must be performed within 28 days prior to registration
• COHORT 1: Low grade serous ovarian cancer with KRAS, NRAS non-BRAF V600E aMOIs or rare RAF fusions are acceptable
• COHORT 1: No prior MEK inhibitor or CDK4/6 inhibitor therapy
• COHORT 1: Any number of prior therapies permitted
• COHORT 1: No major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 2 weeks prior to registration
• COHORT 1: No prior cancer-directed therapy within 28 days prior to registration. Patients may have received cancer-directed hormonal therapy up to 14 days prior to registration
• COHORT 2: Low grade serous ovarian cancer
• COHORT 2: Prior progression of disease on a MEK inhibitor (prior binimetinib permitted)
• COHORT 2: If patient has previously received binimetinib, they cannot have required dose reduction or discontinuation of binimetinib due to adverse events
• COHORT 2: No prior receipt of a CDK4/6 inhibitor
• COHORT 2: No major surgery within 4 weeks (excluding placement of vascular access), minor surgery within 2 weeks, or palliative radiotherapy within 2 weeks prior to registration

Where it is running

• University of South Alabama Mitchell Cancer Institute — Mobile, Alabama, United States
• Providence Alaska Medical Center — Anchorage, Alaska, United States
• UC San Diego Health System - Encinitas — Encinitas, California, United States
• UC San Diego Moores Cancer Center — La Jolla, California, United States
• VA Palo Alto Health Care System — Palo Alto, California, United States
• UC San Diego Medical Center - Hillcrest — San Diego, California, United States
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States
• Poudre Valley Hospital — Fort Collins, Colorado, United States
• Cancer Care and Hematology-Fort Collins — Fort Collins, Colorado, United States
• UCHealth Greeley Hospital — Greeley, Colorado, United States
• Medical Center of the Rockies — Loveland, Colorado, United States
• UM Sylvester Comprehensive Cancer Center at Aventura — Aventura, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Coral Gables — Coral Gables, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Deerfield Beach — Deerfield Beach, Florida, United States
• UF Health Cancer Institute - Gainesville — Gainesville, Florida, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Kendall — Miami, Florida, United States
• UM Sylvester Comprehensive Cancer Center at Plantation — Plantation, Florida, United States
• Saint Alphonsus Cancer Care Center-Boise — Boise, Idaho, United States
• Saint Luke's Cancer Institute - Boise — Boise, Idaho, United States
• Saint Alphonsus Cancer Care Center-Caldwell — Caldwell, Idaho, United States
• Kootenai Health - Coeur d'Alene — Coeur d'Alene, Idaho, United States
• Saint Luke's Cancer Institute - Fruitland — Fruitland, Idaho, United States
• Saint Luke's Cancer Institute - Meridian — Meridian, Idaho, United States
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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