Background and Rationale

Malignant tumors driven by viral infection exhibit low response rates to standard therapies, creating an urgent need for novel treatment options. Various viruses, including Epstein‑Barr virus (EBV) and human papillomavirus (HPV), contribute to lymphomas, hepatocellular carcinoma, cervical cancer, and other malignancies. These cancers are challenging to treat due to a combination of immune suppression and alterations in the tumor microenvironment.

Study Objectives and Design

This Phase 1 trial explores the safe dosage of pomalidomide in combination with nivolumab. Pomalidomide is an immunomodulatory agent, and nivolumab is an immune‑checkpoint inhibitor. Patients receive pomalidomide orally for 21 days of a 28‑day cycle and a single intravenous infusion of nivolumab, with up to 24 cycles permitted. The study enrolls patients with virus‑associated cancers as well as individuals living with HIV to assess broad applicability.

Expected Benefits and Differentiation

Pomalidomide modulates signaling between tumor cells and immune cells to enhance antitumor activity, while nivolumab blocks the PD‑1 pathway to restore T‑cell function. The combination is expected to produce synergistic effects beyond those of either agent alone. Notably, the regimen may offer a lower toxicity profile compared with conventional chemotherapy, potentially providing a safer option for immunocompromised patients such as those with HIV.

Potential Risks and Limitations

As a Phase 1 study, the primary focus is safety rather than efficacy, and conclusions regarding long‑term survival cannot yet be drawn. The heterogeneity of viral etiologies and cancer types adds complexity to data interpretation. Additionally, the high cost of pomalidomide and nivolumab presents a challenge for achieving price competitiveness upon commercialization.