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

Abstract

Purpose: 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.

Patients and methods: 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.

Results: 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.

Conclusion: Intralesional nivolumab was safe and well-tolerated in this population of men with limited cutaneous KS.