Background:
* There is an unmet need for less toxic and more effective treatments for virus-associated malignancies.
* Pomalidomide induces polyfunctional T cell, NK cell, and dendritic cell activation.
* Pomalidomide has shown promising activity in Kaposi sarcoma, likely due in part to immune modulation.
* Downregulation and/or deregulation of immune surface markers by viruses can thwart immunologic therapy, which may be prevented or reversed by pomalidomide.
* PD-L1 is expressed in virus-associated malignancies and modulation of PD-1 signaling is a promising approach to treatment of virus-associated malignancies.
* Checkpoint inhibitors used alone have been shown to have some activity in certain virus-induced tumors (e.g. Hodgkin and non-Hodgkin lymphomas, Merkel cell carcinoma, and HPV-associated nasopharyngeal cancer). It is thus rational to explore combination strategies that overcome viral-mediated immune evasion and provide potentially better immunologic anti-tumor activity.
Objectives:
-Assess the safety and tolerability of pomalidomide plus nivolumab (Pom/Nivo) in participants with virus-associated malignancies
Eligibility:
* Age \>=18 years
* Histologically or cytologically proven selected virus-associated tumors that are systemic, metastatic or locally advanced and not amenable to curative treatment options or relapsed/refractory to first-line therapy
* For solid tumors or hematologic malignancies at least one measurable disease
* At least five measurable cutaneous KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy to these measurable lesions.
* ECOG Performance Status (PS) \<= 2
* Participants must be willing to give informed consent.
* Participants can be HIV positive or negative.
* Antiretroviral therapy (ART) for HIV+ patients
* Participants receiving other investigational agents will not be eligible.
Design:
* This is a Phase I study assessing the safety and efficacy of a fixed dose of nivolumab combined with pomalidomide.
* In the escalation phase of the study, up to 12 evaluable participants with virus-associated malignancies will be treated with pomalidomide in a 3+3 dose escalation schema to identify a maximum tolerated dose (MTD).
* In the expansion phase of the study, up to 30 evaluable participants will be treated with pomalidomide at the MTD. Of these, 6 participants must have a virus-associated malignancy, 12 must have a KS diagnosis and 12 must have EBV and/or KSHV-associated
lymphomas.
* Nivolumab will be administered IV at a dose of 480 mg at day one of each cycle, except for cycle one when it will be administered on day 8. One cycle equals 28 days.
* Pomalidomide will be administered as an oral planned starting dose of 3 mg daily (dose escalation) or at an MTD of 4 mg (dose expansion). Pomalidomide will be given from day 1 to day 21 of each cycle.
* Participants will receive therapy up to 24 cycles or until unacceptable toxicity, clinical progression, the participant s request to discontinue therapy, or PI decision.
