Phase I Trial to Evaluate the Safety of Intralesional Nivolumab Therapy for Limited Cutaneous Kaposi Sarcoma - PubMed (original) (raw)

. 2025 Jul 7;2(1):e2400098.

doi: 10.1200/OA-24-00098. eCollection 2025.

Alexander Bang 2, Sona Chowdhury 1, Kieron S Leslie 1, Ursula E Lang 1, Michiko Shimoda 1, Timothy J Henrich 1, Rebecca Hoh 1, Steve G Deeks 1, Chao Wang 1, Amelia N Deitchman 1, Paul Couey 1, Toby Maurer 3

Affiliations

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

Chia-Ching J Wang et al. JCO Oncol Adv. 2025.

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.

© 2025 by American Society of Clinical Oncology.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to https://ascopubs.org/authors. Chia-ching J. Wang Stock and Other Ownership Interests: Gilead Sciences Michiko Shimoda Patents, Royalties, Other Intellectual Property: I am a co-inventor of patent applications entitled “Transcription Active Complex Targeting Cancer Drug from Viral Protein Sequence” and “vIL-6 for cancer therapy” (Inst) Timothy J. Henrich Consulting or Advisory Role: Roche Research Funding: Merck (Inst) Steve G. Deeks Stock and Other Ownership Interests: Tendel Honoraria: ViiV Healthcare, Pfizer, Hologic, AbbVie, Enanta Research Funding: Gilead Sciences (Inst), Aerium (Inst), Vir (Inst) Amelia N. Deitchman Employment: Denali Therapeutics (I) Stock and Other Ownership Interests: Denali Therapeutics (I), Amgen (I) Patents, Royalties, Other Intellectual Property: Dosage regimen for anti-EGFRVIII agents (I) Paul Couey Employment: Revolution Medicines (I) Stock and Other Ownership Interests: Revolution Medicines (I) Toby Maurer Employment: MDA Leadership: MDA Stock and Other Ownership Interests: Maurer Dermatology Associates Honoraria: Symposia Medicus, L'oreal, ACTHIV, IAS USA Consulting or Advisory Role: Medweb No other potential conflicts of interest were reported. Toby Maurer Employment: MDA Leadership: MDA Stock and Other Ownership Interests: Maurer Dermatology Associates Honoraria: Symposia Medicus, L'oreal, ACTHIV, IAS USA Consulting or Advisory Role: Medweb No other potential conflicts of interest were reported. Toby Maurer Employment: MDA Leadership: MDA Stock and Other Ownership Interests: Maurer Dermatology Associates Honoraria: Symposia Medicus, L'oreal, ACTHIV, IAS USA Consulting or Advisory Role: Medweb No other potential conflicts of interest were reported.

Figures

FIG 1.

FIG 1.

Examples of KS skin lesions before and after intralesional nivolumab treatment. KS, Kaposi sarcoma.

FIG 2.

FIG 2.

Cutaneous intralesional nivolumab leads to significant reduction in the percentage of circulating memory (non-naïve) T cells expressing PD-1. Study treatment led to a transient but significant reduction in the percentage of PD-1-expressing (A) CD4+ T cells and (C) CD8+ T cells as well as detection of (B and D) PD-1+ lymphocyte-bound nivolumab. Post-nivolumab = sampling at 2 weeks following the second dose of nivolumab. Off-nivolumab = sampling at the end of study 26-week time point. Bars and lines represent mean values and 95% CIs, respectively. *P < .05, **P < .01, and ***P < .001 by two-sided nonparametric Friedman tests with Dunn correction for multiple comparisons. One participant did not have sufficient cells available from the off-nivolumab time point flow cytometry analysis.

FIG A1.

FIG A1.

Flow cytometric gating strategy for PD-1 expression and nivolumab binding on non-naïve (memory) CD8+ and CD4+ T cells. PD-1MH4 antibody clone does not interact with nivolumab binding.

FIG A2.

FIG A2.

Examples of PD-1/PD-L1 stains of skin biopsies of KS tumors. KS, Kaposi sarcoma.

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