Pilot Trial of Nivolumab plus Cabozantinib for Advanced Solid Tumors in Patients with HIV infection

Albert Einstein College Of Medicine, Bronx NY

Investigators

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Abstract

PROJECT SUMMARY/ABSTRACT The tolerability and efficacy of immunotherapy (either alone or in combination treatment) remains largely unknown in patients living with HIV on antiretrovirals (ART), who had generally been excluded from previous trials. We recently compiled one of the largest experiences among patients with HIV infection and lung cancer. Our data showed a remarkably low expression of PD- L1 in this patient population. We also found that alternative immune checkpoints were widely expressed in solid tumors. Intriguingly, the majority of PD-L1 negative lung cancers expressed alternative immune checkpoints, implicating their potential roles in mediating immune escape mechanisms within the tumor microenvironment, apart from the PD-1/PD-L1 axis. As an anti-angiogenic agent, Cabozantinib is also associated with an immune permissive tumor environment with immune-stimulatory activities. Its antitumor activity has been observed in thyroid cancer, renal cell and hepatocellular carcinomas, as well as Kaposi sarcoma (KS) and other solid tumors. The combination of Cabozantinib with Nivolumab may modify the tumor microenvironment and reverse the resistance to immunotherapy. In the proposed study, we will determine the safety profile and clinical benefits of the combined treatment with Nivolumab and Cabozantinib in HIV infected patients with advanced solid tumors (especially KS). The Primary objectives are to determine the safety of combined Nivolumab and Cabozantinib in HIV patients with advanced solid tumors and to determine the feasibility to deliver the combined Nivolumab and Cabozantinib (40mg daily) for a minimum of 4 cycles in at least 75% of the subjects or to achieve a confirmed objective response. Six patients will be enrolled in the safety run-in cohort. At the expansion cohort, 12 additional subjects with KS would be enrolled to gather more data on safety and correlative studies. We will also conduct correlative analyses to expand our understanding of the underlying biology, predictive biomarkers and treatment resistance in this group of patients. We expect that the combined treatment of Nivolumab and Cabozantinib is safe and feasible in HIV patients with solid tumors. Moreover, we anticipate that the combination has clinical activity in this unique and understudied patient population.