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

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.

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 courseDisease must be metastatic or locally advanced and surgically unresectable, in the opinion of the treating investigatorNote: 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 requiredELIGIBILITY 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 radiationELIGIBILITY CRITERIA (STEP 1): Patients may have received any number of prior systemic treatment lines for DDLPS, including noneELIGIBILITY 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 replacementELIGIBILITY CRITERIA (STEP 1): Patients must have completed all prior anti-cancer treatment, including radiation, >= 14 days prior to registrationELIGIBILITY CRITERIA (STEP 1): Age >= 18 yearsELIGIBILITY CRITERIA (STEP 1): Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2ELIGIBILITY CRITERIA (STEP 1): Absolute neutrophil count (ANC) >= 1000/mm^3ELIGIBILITY CRITERIA (STEP 1): Platelet count >= 100,000/mm^3ELIGIBILITY CRITERIA (STEP 1): Hemoglobin >= 9 g/dLELIGIBILITY CRITERIA (STEP 1): Creatinine clearance (CrCl) >= 30 mL/minELIGIBILITY 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 ULNELIGIBILITY 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 infarctionELIGIBILITY CRITERIA (STEP 1): For patients with evidence of chronic hepatitis B (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicatedELIGIBILITY 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 loadELIGIBILITY 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 trialELIGIBILITY 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 therapyELIGIBILITY 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 eligibleELIGIBILITY CRITERIA (STEP 1): Patients must be able to swallow oral medicationsRE-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 aboveRE-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 criteriaExclusion 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 antibodiesELIGIBILITY 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 requiredELIGIBILITY 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 equivalentELIGIBILITY 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 requirementsELIGIBILITY CRITERIA (STEP 1): Patients may not require the use of chronic steroids in excess of 10 mg prednisone daily or equivalentELIGIBILITY 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 weeksELIGIBILITY 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 agentsRE-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 1Patients 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 replacementNote: 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 antibodiesRE-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