Testing the Addition of Cemiplimab to Palbociclib for the Treatment of Advanced Dedifferentiated Liposarcoma

Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8 Clinical Trial

Official title:

Official Title A Randomized Phase 2 Trial With a Safety Lead-In to Evaluate Palbociclib Versus Palbociclib and Cemiplimab for the Treatment of Advanced Dedifferentiated Liposarcoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05694871
• Other study ID #: A092107
• Secondary ID: NCI-2022-08568
• Status: Recruiting
• Phase: Phase 2
• Start date: May 30, 2023
• Est. completion date: May 31, 2027

Study information

• Verified date: May 2024
• Source: Alliance for Clinical Trials in Oncology
• Contact: Matthew Ingham, MD
• Phone: 646-317-7141
• Email: mi2337[@]cumc.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial compares the effect of treatment with palbociclib alone to treatment with palbociclib plus cemiplimab for treating patients with dedifferentiated liposarcoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Palbociclib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Cemiplimab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. The combination of these two drugs may be more effective in shrinking or stabilizing advanced dedifferentiated liposarcoma compared to palbociclib alone.

Description:

PRIMARY OBJECTIVES:

I. To perform a safety lead-in among 6 patients to confirm that the combination of palbociclib and cemiplimab is safe and tolerable.

II. To evaluate whether palbociclib in combination with cemiplimab (Arm 2) demonstrates a superior progression-free survival (PFS) compared to palbociclib monotherapy (Arm 1) for patients with advanced dedifferentiated liposarcoma (DDLPS).

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile in and across each treatment arm as determined by both Common Terminology Criteria for Adverse Events (CTCAE) and Patient Reported Outcomes (PRO)-CTCAE criteria.

II. To evaluate and compare the objective response rate (ORR) and duration of response (DOR) in and across each treatment arm.

III. To evaluate and compare the overall survival (OS) in and across each treatment arm.

IV. To evaluate and compare progression-free rate at 8 weeks (PFR8) in and across each treatment arm.

EXPLORATORY OBJECTIVES:

I. To collect genomic sequencing data previously collected as standard of care, including data on CDK4 copy number (as determined by fluorescence in situ hybridization [FISH] or other molecular testing).

II. To conduct multiplex immunohistochemistry using archival tumor tissue (where available) to define densities of infiltrating immune cell subsets and tumor and immune cell major histocompatibility complex (MHC) and PD-L1 expression.

III. To perform an exploratory analysis to evaluate for any relationship between CDK4 copy number and (a) the tumor immune microenvironment as defined by multiplex immunohistochemistry and (b) clinical outcomes from study treatment.

IV. To explore efficacy and toxicity endpoints, including PFS and ORR, for patients who progress on palbociclib monotherapy and crossover to the palbociclib plus cemiplimab combination.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive palbociclib orally (PO) on study. Patients will be allowed to cross over to Arm II following documentation of disease progression. Patients undergo magnetic resonance imaging (MRI) or computed tomography (CT) scans throughout the trial. Patients may also undergo blood sample collection on study.

ARM II: Patients receive palbociclib PO and cemiplimab intravenously (IV) on study. Patients undergo MRI or CT scans throughout the trial. Patients may also undergo blood sample collection on study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ELIGIBILITY CRITERIA (STEP 1): Patients must have histologically documented dedifferentiated liposarcoma (DDLPS). Patients with mixed well-differentiated/dedifferentiated liposarcoma (WD/DD LPS) tumors are eligible provided there is a histologically confirmed DDLPS component at some point during the treatment course

• Disease must be metastatic or locally advanced and surgically unresectable, in the opinion of the treating investigator

• Note: Intact retinoblastoma protein (RB) can be assumed in DDLPS. In a query of project Genomics Evidence Neoplasia Information Exchange (GENIE) (American Association for Cancer Research [AACR]), including 286 DDLPS tumors, the rate of RB1 mutation in DDLPS was 1.37%. Therefore, molecular testing to determine intact Rb is not required

• ELIGIBILITY CRITERIA (STEP 1): Patients must have at least one lesion that is measurable per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria to be eligible for this study. Previously radiated lesions should not be used as target lesions unless there is documented evidence of disease progression of that lesion after radiation

• ELIGIBILITY CRITERIA (STEP 1): Patients may have received any number of prior systemic treatment lines for DDLPS, including none

• ELIGIBILITY CRITERIA (STEP 1): Patients must have recovered to baseline or =< grade 1 per CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy, and with the exceptions of fatigue (which must be =< grade 2), alopecia and/or endocrinopathies related to prior immunotherapy which are controlled with hormone replacement

• ELIGIBILITY CRITERIA (STEP 1): Patients must have completed all prior anti-cancer treatment, including radiation, >= 14 days prior to registration

• ELIGIBILITY CRITERIA (STEP 1): Age >= 18 years

• ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

• ELIGIBILITY CRITERIA (STEP 1): Absolute neutrophil count (ANC) >= 1000/mm^3

• ELIGIBILITY CRITERIA (STEP 1): Platelet count >= 100,000/mm^3

• ELIGIBILITY CRITERIA (STEP 1): Hemoglobin >= 9 g/dL

• ELIGIBILITY CRITERIA (STEP 1): Creatinine clearance (CrCl) >= 30 mL/min

• ELIGIBILITY CRITERIA (STEP 1): Total bilirubin =< 1.5 x upper limit of normal (ULN)

• ELIGIBILITY CRITERIA (STEP 1): Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x ULN

• ELIGIBILITY CRITERIA (STEP 1): Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible, patients should be class IIB or better. Furthermore, patients may not have an uncontrolled ventricular arrhythmia or recent (within 3 months) myocardial infarction

• ELIGIBILITY CRITERIA (STEP 1): For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• ELIGIBILITY CRITERIA (STEP 1): Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently receiving treatment, they are eligible if they have an undetectable HCV viral load

• ELIGIBILITY CRITERIA (STEP 1): Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• ELIGIBILITY CRITERIA (STEP 1): Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Patients participating on this trial may not be receiving other anti-neoplastic therapies and there should be no anticipated need for such therapy

• ELIGIBILITY CRITERIA (STEP 1): Patients with treated brain metastases that are non-progressing are eligible if follow-up brain imaging performed at least 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are not eligible

• ELIGIBILITY CRITERIA (STEP 1): Patients must be able to swallow oral medications

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): In order to cross over to Arm 2, patients must meet the same eligibility criteria as described above

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2):

Patients must have demonstrated progression of disease on palbociclib monotherapy (Arm 1) per RECIST version 1.1 criteria

Exclusion Criteria:

• ELIGIBILITY CRITERIA (STEP 1): Patients may not have received prior treatment with CDK4/6 inhibitors (including, but not limited to: palbociclib, ribociclib or abemaciclib) or anti-PD-1/anti-PD-L1 antibodies

• ELIGIBILITY CRITERIA (STEP 1): Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects

• Therefore, for women of childbearing potential only, a negative serum pregnancy test done =< 7 days prior to registration is required

• ELIGIBILITY CRITERIA (STEP 1): Patients must not have an active autoimmune disease with the exception of vitiligo, well-controlled asthma or allergic rhinitis, type 1 diabetes, psoriasis or hypothyroidism. Patients with a history of adrenal insufficiency are eligible if on a stable dose of prednisone =< 10 mg or equivalent

• ELIGIBILITY CRITERIA (STEP 1): Patients must not have an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any other condition that would limit compliance with study requirements

• ELIGIBILITY CRITERIA (STEP 1): Patients may not require the use of chronic steroids in excess of 10 mg prednisone daily or equivalent

• ELIGIBILITY CRITERIA (STEP 1): Patients may not require concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir). The required washout period prior to re-registration 2 weeks

• ELIGIBILITY CRITERIA (STEP 1): Patients may not require concomitant use of known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort). The required washout period prior to re-registration is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2):

Patients may not have experienced a grade 3 or higher non-hematologic adverse event deemed clinically significant in the opinion of the treating investigator, or have discontinued palbociclib due to toxicity, while participating on Arm 1

• Patients must also have recovered to baseline or =< grade 1 per CTCAE version 5.0 from toxicity related to Arm 1 treatment, unless adverse events are clinically nonsignificant and/or stable on supportive therapy, and with the exceptions of fatigue (which must be =< grade 2), alopecia and/or endocrinopathies related to prior immunotherapy which are controlled with hormone replacement

• Note: Patients who underwent dose reduction of palbociclib during treatment on Arm 1 will begin treatment on Arm 2 at the same dose (i.e. dose re-escalation is not allowed)

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2):

Patients may not have received prior treatment with anti-PD-1/anti-PD-L1 antibodies

• RE-REGISTRATION ELIGIBILITY CRITERIA (FOR STEP 2 CROSSOVER FROM ARM 1 TO ARM 2): Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects * Therefore, for women of childbearing potential only, a negative serum pregnancy test done =< 7 days prior to re-registration is required

Related Conditions & MeSH terms

• Liposarcoma
• Metastatic Dedifferentiated Liposarcoma
• Sarcoma
• Stage III Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8
• Stage IV Soft Tissue Sarcoma of the Trunk and Extremities AJCC v8

Intervention

Drug:
• Palbociclib
Given PO

Biological:
• Cemiplimab
Given IV

Procedure:
• Magnetic Resonance Imaging
undergo MRI
• Computed Tomography
Undergo a CT Scan
• Biospecimen collection
Undergo blood sample collection

Other:
• Questionnaire Administration
Ancillary Studies

Locations

Country	Name	City	State
United States	Kaiser Permanente-Deer Valley Medical Center	Antioch	California
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Mission Hope Medical Oncology - Arroyo Grande	Arroyo Grande	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	UH Seidman Cancer Center at UH Avon Health Center	Avon	Ohio
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Nebraska Medicine-Bellevue	Bellevue	Nebraska
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Mercy Cancer Center - Carmichael	Carmichael	California
United States	Mercy San Juan Medical Center	Carmichael	California
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Geauga Hospital	Chardon	Ohio
United States	Northwestern University	Chicago	Illinois
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	Saint Francis Cancer Center	Colorado Springs	Colorado
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Heartland Oncology and Hematology LLP	Council Bluffs	Iowa
United States	Methodist Jennie Edmundson Hospital	Council Bluffs	Iowa
United States	Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ	Council Bluffs	Iowa
United States	Carle at The Riverfront	Danville	Illinois
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Northwestern Medicine Cancer Center Kishwaukee	DeKalb	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Illinois CancerCare-Dixon	Dixon	Illinois
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Kaiser Permanente Dublin	Dublin	California
United States	Mercy Medical Center	Durango	Colorado
United States	Southwest Oncology PC	Durango	Colorado
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Mercy Cancer Center - Elk Grove	Elk Grove	California
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Hunterdon Medical Center	Flemington	New Jersey
United States	Kaiser Permanente-Fremont	Fremont	California
United States	Fresno Cancer Center	Fresno	California
United States	Kaiser Permanente-Fresno	Fresno	California
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Northwestern Medicine Cancer Center Delnor	Geneva	Illinois
United States	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois
United States	Northwestern Medicine Glenview Outpatient Center	Glenview	Illinois
United States	Northwestern Medicine Grayslake Outpatient Center	Grayslake	Illinois
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois
United States	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii
United States	M D Anderson Cancer Center	Houston	Texas
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Mercyhealth Hospital and Cancer Center - Janesville	Janesville	Wisconsin
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Marshfield Medical Center - Ladysmith	Ladysmith	Wisconsin
United States	Northwestern Medicine Lake Forest Hospital	Lake Forest	Illinois
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Saint Joseph Hospital	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Saint Joseph London	London	Kentucky
United States	Longmont United Hospital	Longmont	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Mercy Cancer Center	Merced	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Kaiser Permanente-Modesto	Modesto	California
United States	Saint Joseph Mount Sterling	Mount Sterling	Kentucky
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	Marshfield Medical Center - Neillsville	Neillsville	Wisconsin
United States	Jersey Shore Medical Center	Neptune	New Jersey
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	HSHS Saint Elizabeth's Hospital	O'Fallon	Illinois
United States	Kaiser Permanente Oakland-Broadway	Oakland	California
United States	Kaiser Permanente-Oakland	Oakland	California
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Nebraska Cancer Specialists/Oncology Hematology West PC - MECC	Omaha	Nebraska
United States	Nebraska Medicine-Village Pointe	Omaha	Nebraska
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Oncology Associates PC	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Northwestern Medicine Orland Park	Orland Park	Illinois
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Parker Adventist Hospital	Parker	Colorado
United States	University Hospitals Parma Medical Center	Parma	Ohio
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California
United States	Kaiser Permanente- Marshall Medical Offices	Redwood City	California
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	Kaiser Permanente-Richmond	Richmond	California
United States	VCU Massey Cancer Center at Stony Point	Richmond	Virginia
United States	Virginia Cancer Institute	Richmond	Virginia
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Mercy Cancer Center - Rocklin	Rocklin	California
United States	Rohnert Park Cancer Center	Rohnert Park	California
United States	Kaiser Permanente-Roseville	Roseville	California
United States	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California
United States	Kaiser Permanente Downtown Commons	Sacramento	California
United States	Mercy Cancer Center - Sacramento	Sacramento	California
United States	South Sacramento Cancer Center	Sacramento	California
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Siteman Cancer Center-South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente-San Francisco	San Francisco	California
United States	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California
United States	Kaiser Permanente San Leandro	San Leandro	California
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Kaiser San Rafael-Gallinas	San Rafael	California
United States	UH Seidman Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Kaiser Permanente-Santa Rosa	Santa Rosa	California
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	Kaiser Permanente Cancer Treatment Center	South San Francisco	California
United States	Kaiser Permanente-South San Francisco	South San Francisco	California
United States	Memorial Medical Center	Springfield	Illinois
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Kaiser Permanente-Stockton	Stockton	California
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Carle Cancer Center	Urbana	Illinois
United States	Kaiser Permanente Medical Center-Vacaville	Vacaville	California
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Northwestern Medicine Cancer Center Warrenville	Warrenville	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	ThedaCare Cancer Care - Waupaca	Waupaca	Wisconsin
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	UH Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Northwestern Medicine Central DuPage Hospital	Winfield	Illinois
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin
United States	Woodland Memorial Hospital	Woodland	California
United States	Rush-Copley Healthcare Center	Yorkville	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	CDK4 copy number	Explore data on CDK4 copy number (by fluorescence in situ hybridization [FISH] or other molecular testing) through plots and summary statistics.	Up to 2 years
Other	Infiltrating immune cell subsets and tumor and immune cell major histocompatibility complex (MHC) and PD-L1 expression	Conduct multiplex immunohistochemistry using archival tumor tissue (where available) to summarize densities of infiltrating immune cell subsets and tumor and immune cell MHC and PD-L1 expression.	Up to 2 years
Other	Relationship between CDK4 copy number and the tumor immune microenvironment and clinical outcomes	Explore the relationship between CDK4 copy number and (a) the tumor immune microenvironment as defined by multiplex immunohistochemistry and (b) clinical outcomes from study treatment Clinical endpoints include PFS, objective response rate, OS, PFR8, and DoR. Cox regression will be used on time-to-event outcomes and T-test on binary outcomes	up to 2 years
Other	Efficacy and toxicity endpoints	Explore the efficacy and toxicity endpoints for patients who progress on palbociclib monotherapy and crossover to the palbociclib plus cemiplimab combination A sensitivity analysis will be conducted to see how crossover effects overall survival. Rate and severity of adverse events will be used to assess differences between crossover and non-crossover patients.	Up to 2 years
Primary	Progression-free survival (PFS)	Efficacy analyses will be based on intention to treat principles. PFS will be compared between the two treatment arms using Kaplan-Meier methods. The hazard ratio, median PFS, and estimated PFS rates at 12, 24, 36, and 48 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. Cox proportional hazards models will also be used to assess the impact of treatment arm on PFS when stratifying on the stratification factors.	The time from randomization to the first documentation of disease progression or death, assessed up to 48 months.
Secondary	Incidence of adverse events	Patients will be evaluated for adverse events using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 5.0. Summary statistics (e.g., mean, median, standard deviation) and frequency tables will be used to describe the distributions of adverse events. Rates of adverse events occurring in the treatment arm will be compared to the control arm with chi-squared tests (or suitable alternative) used for comparisons where applicable. Tolerability will also be evaluated, summarizing rates of dose delays or modifications, reasons patients end treatment, and time to end of active treatment.	Up to 2 years
Secondary	Duration of response (DoR)	Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a complete response or partial response 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.	up to 2 years
Secondary	Overall survival (OS)	Defined as the time from randomization to death due to any cause. Patients who are alive will be censored at last follow-up for OS. The distribution of survival time will be estimated using the method of Kaplan-Meier. OS will be compared between treatment arms using the log-rank test. OS medians, survival rates and hazard ratio will be estimated along with 95% confidence intervals.	up to 2 years
Secondary	Progression free rate at 8 weeks (PFR8)	Defined as the proportion of evaluable patients who are alive and without evidence of disease progression 8 weeks after initiation of study therapy. The final PFR8 point estimate and corresponding 95% confidence interval calculated using Clopper-Pearson method.	At 8 weeks