Phase I Trial to Evaluate the Safety of Intralesional Nivolumab Therapy for Limited Cutaneous Kaposi Sarcoma.

Abstract

Intralesional vinblastine can induce regression of Kaposi sarcoma (KS), but it is often painful. We conducted a phase I trial to evaluate the safety and tolerability of intralesional injections of nivolumab to treat cutaneous KS. We enrolled participants with limited cutaneous KS and injected 1 mL (10 mg) of nivolumab into target KS lesions once every 2 weeks for four doses, with optional extension to total of eight doses. Skin biopsy of a target KS lesion was performed at screening and at week 26. The primary end point was safety; the secondary end point was KS response by AIDS Clinical Trials Group criteria. Between May 2018 and December 2020, 12 cis-gender men (six living with HIV and six without HIV) were enrolled. Baseline median CD4⁺ T-cell count was 550 and 706 cells/uL for those with and without HIV, respectively. No grade 3 or higher treatment-related adverse events (including autoimmune events) were reported. Three participants without HIV had complete resolution of the injected lesion(s). All participants had a reduction of HHV-8-positive cells in their skin biopsies at week 26. Four participants had a relative increase in the infiltrating CD8⁺ T cells in skin biopsies after treatment. PD-1 and PD-L1 by immunohistochemistry did not change between the pre- and post-treatment skin biopsies. The percentage of circulating CD4⁺ and CD8⁺ T cells expressing PD-1 decreased from 23.8% to 19.2% before treatment to 10.9% and 9.4% before the third intralesional nivolumab injection, respectively. The frequency of PD-1 expressing lymphocytes returned to baseline level at 26 weeks after the last injection. Intralesional nivolumab was safe and well-tolerated in this population of men with limited cutaneous KS.