Active, not recruitingNCT05554367Updated Aug 21, 2026

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

A Phase 2 interventional study of Binimetinib and Biopsy Procedure in Exocrine Pancreas Carcinoma, Malignant Solid Neoplasm and Ovarian Low Grade Serous Adenocarcinoma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 265 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-21.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 199
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

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.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine whether palbociclib and binimetinib combination therapy improves progression free survival (PFS) compared to binimetinib alone in patients with MEK-inhibitor naive low-grade serous ovarian cancer (LGSOC) harboring MAP kinase activation (KRAS/NRAS/non BRAF V600E mutation). (Cohort 1) II. To determine whether palbociclib and binimetinib improves clinical activity in comparison to historical control, as measured by objective response rate (ORR), in women with LGSOC whose disease has previously progressed on a MEK inhibitor. (Cohort 2) III. To determine whether palbociclib and binimetinib combination therapy improves the objective response rate compared to historical control in patients with pancreatic cancer harboring any KRAS/NRAS/HRAS mutation or non-BRAF V600E aMOIs or rare RAF fusion. (Cohort 3) IV. To determine whether palbociclib and binimetinib combination therapy improves objective response rate compared to historical control in patients with tumors harboring any KRAS/NRAS/HRAS mutations or non-BRAF V600E aMOIs or rare RAF fusions (excluding LGSOC, non-small cell lung cancer [NSCLC], colorectal cancer, pancreatic cancer and melanoma). (Cohort 4)

SECONDARY OBJECTIVES:

I. To determine whether palbociclib and binimetinib combination therapy improves objective response rate (ORR), overall survival (OS), duration of response (DOR), and disease control rate (DCR) compared to binimetinib alone in patients with MEK inhibitor-naïve LGSOC. (Cohort 1) II. Conduct whole-exome sequencing to evaluate concordance with the designated laboratory result. (Cohort 1) III. To assess the clinical activity of palbociclib and binimetinib as measured by PFS, OS, DOR, and DCR in women with LGSOC whose disease has previously progressed on a MEK inhibitor. (Cohort 2) IV. Conduct whole-exome sequencing to evaluate concordance with the designated laboratory result. (Cohort 2) V. To assess the clinical activity of palbociclib and binimetinib as measured by PFS, OS, DOR, and DCR in patients with RAS mutated pancreatic cancer. (Cohort 3) VI. Conduct whole-exome sequencing to evaluate concordance with the designated laboratory result. (Cohort 3) VII. To assess the clinical activity of palbociclib and binimetinib as measured by PFS, OS, DOR, and DCR in patients with RAS mutated cancers, excluding LGSOC, NSCLC, colorectal cancer (CRC), pancreatic cancer and melanoma. (Cohort 4) VIII. Conduct whole-exome sequencing to evaluate concordance with the designated laboratory result. (Cohort 4)

EXPLORATORY OBJECTIVES:

I. Explore thymidine kinase 1 (TK1) activity in response to palbociclib. (Cohort 1) II. Assess the correlation between presence of KRAS mutation and activity of both monotherapy and the combination. (Cohort 1) III. Conduct ribonucleic acid (RNA)-sequencing (seq) to assess determinants of response and resistance. (Cohort 1) IV. Explore changes in plasma RAS allelic burden in KRAS-mutated tumors using circulating tumor deoxyribonucleic acid (ctDNA) and correlate changes with clinical activity. (Cohort 1) V. Explore TK1 activity in response to palbociclib.(Cohort 2) VI. Assess the correlation between presence of KRAS mutation and activity of the combination. (Cohort 2) VII. Conduct RNA-seq to assess determinants of response and resistance. (Cohort 2) VIII. Explore changes in plasma RAS allelic burden in KRAS-mutated tumors using ctDNA and correlate changes with clinical activity. (Cohort 2) IX. Explore TK1 activity in response to palbociclib. (Cohort 3) X. Evaluate changes in deoxyribonucleic acid (DNA), RNA and ctDNA to evaluate concordance with the designated laboratory result and to assess determinants of response, signatures of intrinsic resistance or response and the plasma RAS allelic burden in relation to treatment response, respectively. (Cohort 3) XI. Explore TK1 activity in response to palbociclib. (Cohort 4) XII. Evaluate changes in DNA, RNA and ctDNA to evaluate concordance with the designated laboratory result and to assess determinants of response, signatures of intrinsic resistance or response and the plasma RAS allelic burden in relation to treatment response, respectively. (Cohort 4)

OUTLINE: Patients with KRAS, NRAS, non-BRAF V600E aMOIs or rare RAF fusions LGSOC, naïve to MEK or CDK4/6 inhibitor therapy are randomized to either combination cohort 1 or monotherapy cohort 1. Patients with LGSOC who have received prior MEK inhibitor therapy are assigned to combination cohort 2. Patients with KRAS/NRAS/HRAS/non-V600E a MOIs or rare RAF fusion pancreatic cancer are assigned to combination cohort 3. Patients with all other KRAS/NRAS/HRAS, non -BRAF V600E a MOIs or rare FAR fusion tumor types (excluding LGSOC, NSCLC, CRC, pancreatic, and melanoma) are assigned to combination cohort 4.

COMBINATION COHORTS 1, 2, 3, 4: Patients receive palbociclib orally (PO), once per day (QD) on days 1-21 and binimetinib PO twice per day (BID) on days 1-28 of each cycle. 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 magnetic resonance imaging (MRI), computed tomography (CT), bone scan, and collection of blood samples during screening, on study, and/or during follow up.

MONOTHERAPY COHORT 1: 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.

After completion of study treatment, patients are followed up every 3 months for up to 3 years following registration.

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

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In context

Pancreatic Neoplasms

3,235 studies on the registry are indexed under Pancreatic Neoplasms; 898 are open to participants now.

This study's planned enrollment of 199 is above the median of 46 across 2,424 interventional studies indexed under Pancreatic Neoplasms.

Browse Pancreatic Neoplasms studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,505 studies on the registry; 333 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria:

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
COHORT 2: 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 3: Pancreatic cancer with KRAS/NRAS/HRAS, non-BRAF V600E aMOIs or rare RAF fusions are acceptable
COHORT 3: No prior MEK inhibitor (MEKi) and CDK4/6i therapy
COHORT 3: Progression after at least one line of prior therapy as long as there is no standard therapy available or acceptable to patients that is thought to be of benefit
COHORT 3: Any number of prior therapies are permitted
COHORT 3: 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 3: 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 4: KRAS/NRAS/HRAS non-BRAF V600E aMOIs or rare RAF fusions are acceptable
COHORT 4: No prior MEKi and CDK4/6i therapy and progression after at least one line of prior therapy, as long as there is no standard therapy available or acceptable to patients that is thought to be of benefit
COHORT 4: Any number of prior therapies are permitted
COHORT 4: No more than 6 patients with a given tumor type allowed in this cohort
COHORT 4: Any tumor type, except: LGSOC/NSCLC/CRC/pancreatic/melanoma
COHORT 4: 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 4: 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
Not pregnant and not nursing, because this study involves investigational agents whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 7 days prior to registration is required
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status \< 2
Absolute neutrophil count (ANC) >= 1,500/mm\^3
Platelet count >= 100,000/mm\^3
Hemoglobin > 9 g/dL
Creatinine =\< 1.5 x upper limit of normal (ULN) or calculated (calc.) creatinine clearance >= 30 mL/min as calculated by the Cockcroft-Gault formula
Total bilirubin =\< 1.5 x upper limit of normal (ULN). Patients with Gilbert syndrome may enroll if total bilirubin (bili) \< 3 mg/dL (51 micromole/L)
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
Creatine phosphokinase (CPK) =\< 2.5 x ULN
Patients must be able to swallow oral formulations of the agents
No history of interstitial lung disease. No history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Patients should not have history of bowel perforation or intestinal fistulas in the last 6 months
No patients with the inability to swallow oral medications or impaired gastrointestinal absorption due to gastrectomy or active inflammatory bowel disease
No active skin disorder that has required systemic therapy within the past 1 year
No history of rhabdomyolysis
No concurrent ocular disorders including:
- Subjects with history of glaucoma, history of retinal vein occlusion (RVO), predisposing factors for RVO, including uncontrolled hypertension, uncontrolled diabetes
- Subject with history of retinal pathology or evidence of visible retinal pathology that is considered a risk factor for RVO, intraocular pressure > 21 mm Hg as measured by tonometry, or other significant ocular pathology, such as anatomical abnormalities that increase the risk for RVO
- Subjects with a history of corneal erosion (instability of corneal epithelium), corneal degeneration, active or recurrent keratitis, and other forms of serious ocular surface inflammatory conditions
No patients with a history of hypersensitivity to any of the study drug(s)
No prior allogeneic stem cell or solid organ transplantation
Central nervous system (CNS) metastases must have been treated with local therapy (surgery, radiation, ablation) and patient off of systemic steroids, and brain metastases stable for at least 1 month
No residual Common Terminology Criteria for Adverse Events (CTCAE) >= grade 2 toxicity from any prior anticancer therapy, with the exception of grade 2 alopecia
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Patients whose left ventricular ejection fraction (LVEF) has been evaluated by echocardiography (ECHO)/multigated acquisition scan (MUGA) are excluded if the most recent exam shows an LVEF \< 50%
Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment
No exposure to P-glycoprotein (P-gp) inhibitors or inducers within 14 days prior to the first dose and during the course of therapy
Patients treated with Cohort 1 control treatment binimetinib who experience disease progression may elect to migrate to cohort 2 and receive combination treatment with palbociclib and binimetinib. Patients who choose to do so must meet laboratory values and performance status requirements as above and must be begin treatment within 21 days. For patients who migrate from cohort 1 to cohort 2, the 28-day window restricting prior anti-cancer directed therapies does not apply to prior binimetinib. A new biopsy will not be required for migration, but the optional biopsy at disease progression should be encouraged

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 199 participants (estimated)

Study arms

Experimental
Combination Cohorts 1, 2, 3, 4 (palbociclib, binimetinib)
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.
Drug: Binimetinib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging · Drug: Palbociclib
Experimental
Monotherapy Cohort 1 (binimetinib)
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.
Drug: Binimetinib · Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Bone Scan · Procedure: Computed Tomography · Procedure: Magnetic Resonance Imaging

Interventions

DrugBinimetinib
Given PO
Also known as: ARRY 162, ARRY 438162, ARRY-162, ARRY-438162, ARRY162, ARRY438162, MEK 162, MEK-162, MEK162, Mektovi
ProcedureBiopsy Procedure
Undergo biopsy
Also known as: Biopsy, BIOPSY_TYPE, Bx
ProcedureBiospecimen Collection
Undergo collection of blood samples
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
ProcedureBone Scan
Undergo bone scan
Also known as: Bone Scintigraphy
ProcedureComputed Tomography
Undergo CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography
ProcedureMagnetic Resonance Imaging
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
DrugPalbociclib
Given PO
Also known as: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991, PD0332991

What researchers measure

Primary outcomes

Progression free survival (PFS) (Cohort 1)
Will compare the PFS distributions between those treated with palbociclib and binimetinib vs. binimetinib alone. PFS will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio, median PFS, and estimated PFS rates at 6, 12, 18, 24, and 30 months will be estimated along with corresponding 95% confidence intervals. A log-rank test will be used to compare the PFS distributions between the two treatment arms in this cohort. In an ancillary manner, Cox proportional hazards models will also be used to assess the impact of treatment arm on PFS when stratifying on the stratification factors.
Time frame: Time from randomization date until the time of disease progression or death due to any cause, assessed at 6, 12, 18, 24, and 30 months
Objective response rate (ORR) (Cohort 2)
The Simon optimal design used to evaluate efficacy in terms of the objective response rate after treatment in this population will use a two-stage design.
Time frame: Up to 3 years
ORR (Cohort 3)
The Simon minimax design used to evaluate efficacy in terms of the objective response rate after treatment in this population will use a two-stage design.
Time frame: Up to 3 years
ORR (Cohort 4)
The Simon minimax design used to evaluate efficacy in terms of the objective response rate after treatment in this histology/tumor agnostic population will use a two-stage design.
Time frame: Up to 3 years

Secondary outcomes

Objective response (Cohort 1)
Objective response by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria will be estimated using ORR where ORR is defined as the number of evaluable patients achieving a response (partial response \[PR\] or complete response \[CR\] per RECIST v1.1) during treatment with study therapy divided by the total number of evaluable patients. Rates of response will be compared between treatment arms using a chi-square test (or Fisher's exact test as needed). Point estimates will be generated for objective response rates within each arm along with 95% confidence intervals using the Clopper-Pearson method.
Time frame: Up to 3 years
PFS (Cohorts 2, 3, 4)
Disease progression will be determined based on RECIST 1.1 criteria. PFS will be estimated using the Kaplan-Meier method. The median PFS and corresponding 95% confidence interval will be reported. Patients will be censored at the last disease assessment date if they were alive and progression-free at the time of their last assessment.
Time frame: From study entry to the first of either disease progression or death from any cause, assessed up to 3 years
Overall survival (OS) (All Cohorts)
Patients who are alive at last follow-up will be censored at that time point. The distribution of OS will be estimated using method of Kaplan-Meier. The median OS and 95% confidence interval will be reported.
Time frame: From registration until death due to any cause, assessed up to 3 years
Duration of response (DoR) (All Cohorts)
DoR is defined for all evaluable patients who have achieved an objective response as time from the patient's earliest best objective status is first noted as either a CR or PR to the earliest date progression is documented, or death if no prior evidence of disease progression. The distribution of DoR will be estimated using the method of Kaplan-Meier.
Time frame: From patient's earliest best objective status to earliest date of progression, assessed up to 3 years
Disease control (All Cohorts)
Disease control will be estimated using disease control rate (DCR), which is defined as the patients who experience CR or PR per RECIST 1.1 or maintain stable disease for at least 6 months after randomization divided by the total number of evaluable patients. DCR will be evaluated within cohorts, and for cohort 1 this will also be compared between treatment arms using a chi square test. Point estimates will be generated for disease control rates within each arm along with 95% confidence intervals using the Clopper-Pearson method.
Time frame: Up to 3 years
Incidence of adverse events (AE) (All Cohorts)
All eligible patients that have initiated treatment will be considered evaluable for assessing AE rate(s). Patients will be evaluated for adverse events using the National Cancer Institute's Common Toxicity Criteria for Adverse Events version 5.0. The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the AE(s) to the study treatment will be taken into consideration.
Time frame: Up to 3 years

Other outcomes

TK1 activity (Cohorts 1 and 2)
Will explore TK1 activity before vs. after treatment and how this corresponds and correlates to clinical outcomes after treatment with palbociclib.
Time frame: Up to 3 years
KRAS mutations (Cohorts 1 and 2)
Will characterize patients based on presence of KRAS mutations and how these correspond to efficacy outcomes such as PFS and response to treatment. Further, for cohort 1, will also evaluate how presence of this mutation influences outcomes in patients treated with monotherapy vs. the combination therapy. If numbers are sufficient, will also explore if KRAS mutation has any role as an effect modifier in this setting.
Time frame: Up to 3 years
Determinants of response and resistance (Cohorts 1 and 2)
Will conduct whole-exome sequencing and ribonucleic acid (RNA)-sequencing at baseline, and on optional biopsy upon progression to assess determinants of response and resistance. For cohort 1, concordance of diagnostic tumor mutation profile generated by the designated laboratory, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) mutation profile will be assessed.
Time frame: Up to 3 years
Changes in plasma RAS allelic burden in KRAS-mutated tumors (Cohorts 1 and 2)
Will explore changes in plasma RAS allelic burden in KRAS-mutated tumors using ctDNA and correlate changes with clinical activity.
Time frame: Up to 3 years
TK1 activity (Cohorts 3 and 4)
Will explore TK1 activity before vs. after treatment and how this corresponds and correlates to clinical outcomes after treatment with palbociclib.
Time frame: Up to 3 years
Determinants of response (Cohorts 3 and4)
Will evaluate change in deoxyribonucleic acid (DNA), RNA, and ctDNA. Concordance of diagnostic tumor mutation profile generated by the designated laboratory, the pre-treatment biopsy mutation profile, and the pre-treatment ctDNA mutation profile will be assessed.
Time frame: Up to 3 years
Signatures of intrinsic resistance or response (Cohorts 3 and 4)
Will evaluate change in DNA, RNA, and ctDNA. Concordance of diagnostic tumor mutation profile generated by the designated laboratory, the pre-treatment biopsy mutation profile, and the pre-treatment ctDNA mutation profile will be assessed.
Time frame: Up to 3 years
Plasma RAS allelic burden in in relation to response (Cohorts 3 and 4)
Will evaluate change in DNA, RNA, and ctDNA. Concordance of diagnostic tumor mutation profile generated by the designated laboratory, the pre-treatment biopsy mutation profile, and the pre-treatment ctDNA mutation profile will be assessed.
Time frame: Up to 3 years

Study locations

265 sites

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233, United States
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama 36688, United States
Providence Alaska Medical Center
Anchorage, Alaska 99508, United States
UC San Diego Health System - Encinitas
Encinitas, California 92024, United States
UC San Diego Moores Cancer Center
La Jolla, California 92093, United States
VA Palo Alto Health Care System
Palo Alto, California 94304, United States
UC San Diego Medical Center - Hillcrest
San Diego, California 92103, United States
UCHealth University of Colorado Hospital
Aurora, Colorado 80045, United States
Poudre Valley Hospital
Fort Collins, Colorado 80524, United States
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado 80528, United States
UCHealth Greeley Hospital
Greeley, Colorado 80631, United States
Medical Center of the Rockies
Loveland, Colorado 80538, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida 33442, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida 32610, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida 33324, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho 83706, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho 83712, United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho 83605, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho 83814, United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho 83619, United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho 83642, United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho 83687, United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho 83687, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho 83854, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho 83864, United States
Advocate Good Shepherd Hospital
Barrington, Illinois 60010, United States
Illinois CancerCare-Bloomington
Bloomington, Illinois 61704, United States
Illinois CancerCare-Canton
Canton, Illinois 61520, United States
Illinois CancerCare-Carthage
Carthage, Illinois 62321, United States
Northwestern University
Chicago, Illinois 60611, United States
John H Stroger Jr Hospital of Cook County
Chicago, Illinois 60612, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois 60637, United States
Advocate Illinois Masonic Medical Center
Chicago, Illinois 60657, United States
AMG Crystal Lake - Oncology
Crystal Lake, Illinois 60014, United States
Carle at The Riverfront
Danville, Illinois 61832, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois 62526, United States
Decatur Memorial Hospital
Decatur, Illinois 62526, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois 60115, United States
Illinois CancerCare-Dixon
Dixon, Illinois 61021, United States
Advocate Good Samaritan Hospital
Downers Grove, Illinois 60515, United States
Carle Physician Group-Effingham
Effingham, Illinois 62401, United States
Crossroads Cancer Center
Effingham, Illinois 62401, United States
Advocate Sherman Hospital
Elgin, Illinois 60123, United States
Illinois CancerCare-Eureka
Eureka, Illinois 61530, United States
Illinois CancerCare-Galesburg
Galesburg, Illinois 61401, United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois 60134, United States
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois 60026, United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois 60030, United States
Advocate South Suburban Hospital
Hazel Crest, Illinois 60429, United States
Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois 61443, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois 60045, United States
AMG Libertyville - Oncology
Libertyville, Illinois 60048, United States
Condell Memorial Hospital
Libertyville, Illinois 60048, United States
Illinois CancerCare-Macomb
Macomb, Illinois 61455, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois 61938, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois 60451, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois 62269, United States
Advocate Christ Medical Center
Oak Lawn, Illinois 60453-2699, United States
Advocate Outpatient Center - Oak Lawn
Oak Lawn, Illinois 60453, United States
Northwestern Medicine Orland Park
Orland Park, Illinois 60462, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois 60462, United States
Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois 61350, United States
Advocate High Tech Medical Park
Palos Heights, Illinois 60463, United States
Advocate Lutheran General Hospital
Park Ridge, Illinois 60068, United States
Illinois CancerCare-Pekin
Pekin, Illinois 61554, United States
Illinois CancerCare-Peoria
Peoria, Illinois 61615, United States
Illinois CancerCare-Peru
Peru, Illinois 61354, United States
Illinois CancerCare-Princeton
Princeton, Illinois 61356, United States
Mercyhealth Cancer Institute - Rockford
Rockford, Illinois 61114, United States
Southern Illinois University School of Medicine
Springfield, Illinois 62702, United States
Springfield Clinic
Springfield, Illinois 62702, United States
Springfield Memorial Hospital
Springfield, Illinois 62781, United States
Carle Cancer Center
Urbana, Illinois 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois 60555, United States
Illinois CancerCare - Washington
Washington, Illinois 61571, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa 50023, United States
Mercy Hospital
Cedar Rapids, Iowa 52403, United States
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa 52403, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa 50309, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa 50263, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky 40536, United States
Harold Alfond Center for Cancer Care
Augusta, Maine 04330, United States
Lafayette Family Cancer Center-EMMC
Brewer, Maine 04412, United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine 04074, United States
MaineHealth Cancer Care and IV Therapy - South Portland
South Portland, Maine 04106, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201, United States
Walter Reed National Military Medical Center
Bethesda, Maryland 20889-5600, United States
National Institutes of Health Clinical Center
Bethesda, Maryland 20892, United States
UPMC Western Maryland
Cumberland, Maryland 21502, United States
Dana-Farber Cancer Institute
Boston, Massachusetts 02215, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan 48106, United States
Bronson Battle Creek
Battle Creek, Michigan 49017, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan 48114, United States
Trinity Health Medical Center - Brighton
Brighton, Michigan 48114, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan 48188, United States
Trinity Health Medical Center - Canton
Canton, Michigan 48188, United States

Showing the first 100 of 265 sites across 2 countries.

References and documents

Individual participant data

Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 21, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05554367
Lead sponsor: National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Sep 26, 2022
Start date: Dec 13, 2023
Primary completion: Aug 26, 2028 (estimated)
Completion: Aug 26, 2028 (estimated)
Last update: Aug 21, 2026

Study contacts

Geoffrey I Shapiro

principal investigator · Alliance for Clinical Trials in Oncology

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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