Adenovirus-interferon γ (TG1042) demonstrates good tolerance and efficacy in relapsing primary cutaneous lymphoma (PCL): Final results of a phase I/II multicentric trial

Abstract

7539 Background: Interferons (IFNs), which can offset the Th2 dominance associated with PCL have been successfully used to treat these PCL. Intratumoral (i.t.) injection of TG1042 (a non-replicating recombinant adenovirus with a human IFNγ cDNA insert) induces high local production of IFNγ without severe toxicity associated with systemic delivery. Methods: We undertook a phase I/II multicentric trial of repeated, i.t. injections of TG1042 in patients with advanced primary T cell (CTCL) or B cell (CBCL) CL. One to 3 lesions were injected on day 1, 8, and 15 (a 4-week cycle) and thereafter up to 12 cycles. Immunohistochemistry and quantitative PCR were performed on injected lesions biopsied at baseline and after the 1st cycle. In the phase I, 18 patients were enrolled in 3 successive cohorts at the doses of 3 × 109 viral particles (vp) (n = 3), 3 × 1010 vp (n = 3) and 3 × 1011 vp (n = 12). In the phase II, 18 evaluable patients were planned to be treated at 3 × 1011 vp. Results: To date, enrollment is complete, 39 patients (32 CTCL and 7 CBCL) have been included, 9 of them are still on treatment. Patients received a median of 4 lines of prior therapy. 11 patients were at stage Ib and 16 patients at higher stage. Altogether, 245 injections of TG1042 have been administered. Treatment was well tolerated with 8 grade 3 related adverse events. Injection site reaction and flu like syndrome are the most common adverse events. Histology demonstrates pronounced changes in infiltrate patterns with signs of vasculitis, increased numbers of eosinophils, neutrophils, CD8 and TIA-1+ve cells. CD4/CD8 ratio decreased in most tumors. Transgene-IFNγ mRNA was detected in injected lesions. Gene expression analysis of biopsies and PBMC shows up-regulation of IFNγ genes. Local clinical response has been observed in 17 (including 9 complete responses [CR]) out of 31 evaluable patients. 13 global responses (7 CR) out of 30 evaluable patients have been observed. All 5 evaluable CBCL responded (3 CR). Conclusions: These results demonstrate that TG1042 is well tolerated and presents a potential significant benefit for the treatment of both CTCL and CBCL. A phase II is planned in patients with CBCL to confirm those encouraging results. [Table: see text]