Nivolumab and Cabozantinib in People with HIV and Advanced Solid Tumors: A Pilot Trial and Systematic Review

Abstract Background People living with HIV (PWH) are underrepresented in immune checkpoint inhibitor (ICI) and targeted therapy trials, despite a growing burden of malignancies. Cabozantinib may remodel the tumor microenvironment by reducing immunosuppressive myeloid populations and enhancing cytotoxic T-cell infiltration, thereby augmenting antitumor immunity and providing a biologic rationale for combination with PD-1 blockade. However, prospective data on combined ICI and antiangiogenic strategies in PWH are limited. Methods We conducted a multicenter pilot trial of cabozantinib plus nivolumab in PWH with advanced solid tumors receiving stable antiretroviral therapy. The primary endpoints were safety and feasibility. Secondary endpoints included disease control and longitudinal HIV parameters. To place the trial findings in context, we also conducted a focused systematic review of prospective studies evaluating ICIs and relevant targeted therapies in PWH with cancer. Results Between November 2021 and January 2024, 8 participants were enrolled and 7 initiated treatment (Kaposi sarcoma, n = 5; chondrosarcoma, n = 1; prostate cancer, n = 1). No dose-limiting toxicities occurred. Grade 3 treatment-related adverse events were infrequent; no grade 4 or 5 treatment-related adverse events occurred. Among 6 response-evaluable participants, best overall response was stable disease in 5, including disease stabilization lasting >12 months in 3 heavily pretreated participants. HIV viral load and CD4 counts remained stable during treatment. The literature review supported the feasibility of immune checkpoint inhibition in selected PWH receiving antiretroviral therapy, with the strongest prospective activity signal in Kaposi sarcoma. Conclusion Nivolumab plus cabozantinib had a manageable safety profile without an apparent loss of HIV virologic control in available measurements. Durable disease stabilization occurred in some participants, but antitumor efficacy cannot be determined from this small, heterogeneous cohort. These findings support larger dedicated studies in PWH, particularly in Kaposi sarcoma. Clinical trial registration ClinicalTrials.gov identifier NCT04514484.