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

Inclusion Criteria:

• ELIGIBILITY CRITERIA (STEP 1): Patients must have histologically documenteddedifferentiated liposarcoma (DDLPS). Patients with mixedwell-differentiated/dedifferentiated liposarcoma (WD/DD LPS) tumors are eligibleprovided there is a histologically confirmed DDLPS component at some point duringthe treatment course

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

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

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

• ELIGIBILITY CRITERIA (STEP 1): Patients may have received any number of priorsystemic 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 adverseevents are clinically nonsignificant and/or stable on supportive therapy, and withthe exceptions of fatigue (which must be =< grade 2), alopecia and/orendocrinopathies related to prior immunotherapy which are controlled with hormonereplacement

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

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

• ELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) PerformanceStatus 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)/alanineaminotransferase (ALT) =< 3.0 x ULN

• ELIGIBILITY CRITERIA (STEP 1): Patients with known history or current symptoms ofcardiac disease, or history of treatment with cardiotoxic agents, should have aclinical assessment of cardiac function using the New York Heart AssociationFunctional 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, ifindicated

• 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 arecurrently receiving treatment, they are eligible if they have an undetectable HCVviral load

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

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

• ELIGIBILITY CRITERIA (STEP 1): Patients with treated brain metastases that arenon-progressing are eligible if follow-up brain imaging performed at least 4 weeksafter central nervous system (CNS)-directed therapy shows no evidence ofprogression. Patients with new or progressive brain metastases (active brainmetastases) 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): Inorder to cross over to Arm 2, patients must meet the same eligibility criteria asdescribed 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 withCDK4/6 inhibitors (including, but not limited to: palbociclib, ribociclib orabemaciclib) or anti-PD-1/anti-PD-L1 antibodies

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

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

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

• ELIGIBILITY CRITERIA (STEP 1): Patients must not have an uncontrolled intercurrentillness including, but not limited to, ongoing or active infection, uncontrolledmajor seizure disorder, unstable spinal cord compression, superior vena cavasyndrome, extensive interstitial bilateral lung disease on high resolution computedtomography (HRCT) scan or any other condition that would limit compliance with studyrequirements

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

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

• ELIGIBILITY CRITERIA (STEP 1): Patients may not require concomitant use of knownstrong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin,rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort). The requiredwashout period prior to re-registration is 5 weeks for enzalutamide or phenobarbitaland 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 eventdeemed clinically significant in the opinion of the treating investigator, or havediscontinued 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 areclinically nonsignificant and/or stable on supportive therapy, and with theexceptions of fatigue (which must be =< grade 2), alopecia and/orendocrinopathies related to prior immunotherapy which are controlled withhormone replacement

• Note: Patients who underwent dose reduction of palbociclib during treatment onArm 1 will begin treatment on Arm 2 at the same dose (i.e. dose re-escalationis 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): Notpregnant and not nursing, because this study involves an agent that has knowngenotoxic, mutagenic and teratogenic effects * Therefore, for women of childbearingpotential only, a negative serum pregnancy test done =< 7 days prior tore-registration is required