Phase II Multicenter Study of Talimogene Laherparepvec in Classic or Endemic Kaposi Sarcoma
Status:
Not yet recruiting
Trial end date:
2022-03-01
Target enrollment:
Participant gender:
Summary
Kaposi Sarcoma (KS) is a lymphangioproliferation associated with human herpes virus 8 (HHV8)
promoted by immunosuppression. HIV-related KS and iatrogenic posttransplantation KS are
treated by immune restoration, in association with local or systemic therapies as
chemotherapies if required. Conversely in classic and endemic KS, the underlying relative
immunosuppression cannot be directly targeted. Treatment is poorly codified, mostly based on
surgery or radiotherapy for localized KS. Most aggressive forms with visceral involvement are
treated with chemotherapies or interferon, which give at best 30-60% of transient responses
and may not be well tolerated in elderly patients.
Talimogene laherparepvec is the first oncolytic immunotherapy approved by the FDA, in
metastatic or unresectable melanoma with injectable nodal or cutaneous lesions. It is
designed to induce tumor regression of injected lesions through direct lytic effects, and of
uninjected lesions through induction of systemic antitumor immunity.
In Merkel cell carcinoma (MCC), another virus-induced tumor, treatment with PD-1/PD-L1 axis
inhibitors have proven efficacy, thus providing a proof of principle that immunotherapy could
be effective in virus-induced tumors. Two cases of metastatic MCC successfully treated with
talimogene laherparepvec were recently reported, suggesting that talimogene laherparepvec may
also be an effective therapeutic option. Considering the high immunogenicity of viral
epitopes in KS tumors, the role of the immune evasion in the development of KS, and the
cutaneous manifestations (>90% of patients) that can be easily injected, classic and endemic
KS is a good tumor model to be targeted with talimogene laherparepvec. The main objective is
to assess whether talimogene laherparepvec is clinically inactive (partial+complete response
probability π0<10%) or truly active (partial+complete response probability π1>40%) in classic
and endemic Kaposi sarcoma.