A phase I clinical trial on intratumoral administration of autologous CD1c (BDCA-1)+ myeloid dendritic cells plus talimogene laherparepvec (T-VEC) in patients with advanced melanoma

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Abstract

Background Intratumoral (IT) myeloid dendritic cells (myDC) play a pivotal role in initiating antitumor immune responses and re-licensing of anti-tumor cytotoxic T-lymphocytes within the tumor microenvironment. IT injection of the oncolytic virus T-VEC leads to the release of maturation signals and tumor antigens that can be captured and processed by IT co-administered CD1c (BDCA-1)+ myDC, reinvigorating the cancer immunity cycle. Methods Patients with advanced melanoma who failed standard therapy were eligible for IT injections of ≥1 non-visceral metastasis with T-VEC (10^6 PFU/mL; max total volume of 4 mL) on day 1 followed by IT injection of autologous, non-substantially manipulated CD1c (BDCA-1)+ myDC on day 2. Injection of T-VEC (10^8 PFU/mL; max total volume of 4 mL) was repeated on day 21 and every 14 days thereafter. Patients were treated with 0.5x10^6, 1x10^6, or 10x10^6 CD1c (BDCA-1)+ myDC in cohort-1, -2, and -3, respectively. Primary objectives were safety and feasibility. Repetitive biopsies of treated lesions were performed. Results In this ongoing trial, 2 patients were treated in cohort-1, 2 patients in cohort-2, and 3 patients in cohort-3. Patients received a median of 6 (range 3-10) injections of T-VEC. All patients are evaluable for response. The best overall tumor response (according to iRECIST) was a CR (pathologic CR) and one PR (confirmation pending; pathologic CR of treated lesions). Both patients were treated in cohort-3 and had previously progressed on anti-PD-1 checkpoint inhibition, and one patient also on anti-CTLA-4 therapy. Adverse events include G1 fever in 4 patients, G1-2 flu-like symptoms in 5 patients, transient G1-2 local pain and redness at the injection-site in 3 patients, and G1 gastrointestinal symptoms in 4 patients. The patient with CR developed an asymptomatic G3 eosinophilia during treatment; the patient with PR developed a transient purpuric rash at the site of skin metastases after the first treatment. Multiplexed immune-profiling (Ultivue) of baseline and on-treatment tumor biopsies is ongoing. Conclusions IT co-injection of autologous CD1c (BDCA-1)+ myDC with T-VEC is feasible and tolerable and resulted in encouraging early signs of anti-tumor activity in patients with immune checkpoint inhibitor refractory melanoma who received high dose CD1c (BDCA-1)+ myDC.
Original languageEnglish
JournalJournal for immunotherapy of cancer
Volume7
Publication statusPublished - 6 Nov 2019
EventSociety of Immunotherapy for Cancer - Annual Meeting 2019 - National Harbour, United States
Duration: 6 Nov 201910 Nov 2019

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