Intratumoral (IT) myDC play a pivotal role in initiating anti-tumor immune responses and in "re-licensing” of anti-tumor cytotoxic T-lymphocytes within the tumor microenvironment. IT injection of anti-PD-L1 IgG1 mAb AVE and anti-CTLA-4 IgG1 mAb IPI may reduce the number of regulatory T cells and lyse PD-L1+ tumor cells increasing the release of tumor antigens that can be captured and processed by IT co-administered CD1c (BDCA-1)+ myDC, reinvigorating the cancer immunity cycle.
Patients (pts) with advanced solid tumors who failed standard-of-care treatment were eligible for this phase I trial with IT injections of ≥ 1 non-visceral metastasis with IPI (max total dose of 10 mg) and AVE (max total dose of 40 mg) plus IV NIVO (10 mg) on day 1 followed by IT injection of autologous, non-manipulated CD1c (BDCA-1)+ myDC on day 2. Administration of AVE, IPI, and NIVO was repeated every 14 days thereafter. Primary endpoints were safety and feasibility. Clinical responses were defined according to iRECIST criteria.
In this ongoing trial, 4 pts (3 primary melanoma, 1 epithelial ovarian carcinoma) were treated with IT injection of a median of 30.5x106 (range 10-43x106) CD1c (BDCA-1)+ myDC. A median of 5.5 (range 4-7) study drug administrations were performed. One confirmed partial response was documented in a melanoma patient who previously progressed on immune checkpoint inhibitors. In 2 additional melanoma pts regression of the injected subcutaneous metastases coincided with progression of non-injected metastases. Overall, study treatment was well tolerated and adverse events consisted of transient grade 2 local pain at the injection site in 2 pts, grade 1 pruritus in 2 pts, grade 2 pneumonitis in 1 patient, and pruritus and redness of the skin overlaying the injected lesion in 1 patient.
IT injection of autologous, non-manipulated CD1c (BDCA-1)+ myDC with IT co-injection of AVE and IPI plus IV low-dose NIVO is feasible and tolerable and resulted in encouraging early signs of anti-tumor activity in injected as well as non-injected lesions.
EudraCT: 2017-003280-35.
Universitair Ziekenhuis Brussel.
Kom op Tegen Kanker.
All authors have declared no conflicts of interest.