Abstract
A phase Ib clinical trial on intratumoral administration of autologous CD1c (BDCA-1)+ myeloid dendritic cells (myDC) in combination with ipilimumab (IPI) and avelumab (AVE) plus intravenous low-dose nivolumab (NIVO) in patients with advanced solid tumors.
Author
person
Julia Katharina Schwarze
Universitair Ziekenhuis Brussel, Brussels, Belgium
info_outline
Julia Katharina Schwarze, Gil Awada, Louise Cras, Ramses Forsyth, Ivan Van Riet, Bart Neyns
Full text
Authors
person
Julia Katharina Schwarze
Universitair Ziekenhuis Brussel, Brussels, Belgium
info_outline
Julia Katharina Schwarze, Gil Awada, Louise Cras, Ramses Forsyth, Ivan Van Riet, Bart Neyns
Organizations
Universitair Ziekenhuis Brussel, Brussels, Belgium
Abstract Disclosures
Research Funding
Other Foundation
Background:
Intratumoral (IT) myDC play a pivotal role in initiating antitumor immune responses and "re-licensing” of antitumor cytotoxic T-lymphocytes within the tumor microenvironment. IT injection of anti-PD-L1 IgG
1
mAb AVE and anti-CTLA-4 IgG
1
mAb IPI may reduce the number of regulatory T cells and lyse PD-L1
+
tumor cells, thereby releasing tumor antigens that can be captured and processed by IT co-administered CD1c (BDCA-1)
+
myDC, reinvigorating the cancer immunity cycle.
Methods:
Patients (pts) with advanced solid tumors who failed standard therapy were eligible for 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-substantially 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. Repetitive FNA cytology/IHC of treated lesions was performed.
Results:
In this ongoing trial, 6 pts (3x melanoma, 1x epithelial ovarian carcinoma, 2x triple
negative breast carcinoma) were treated with IT injection of a median of 27,2x10
6
(range 10-43x10
6
) CD1c (BDCA-1)
+
myDC and a median of 5 (range 2-10) study drug administrations. At time of this analysis 3 pts are evaluable for response: an ongoing PR ( > 8 months) was documented in a melanoma pt who previously progressed on PD-1 and CTLA-4 inhibitors. In 2 other melanoma pts regression of the injected metastases coincided with progression of non-injected metastases. Adverse events consisted of transient grade(G)2 local pain at injection site in 2 pts, G1 pruritus in 2 pts, G2 pneumonitis in 1 pt, G1 rash in 1 pt, and pruritus and redness of the skin overlaying the injected lesion in 1 pt. Analysis of cytology/IHC results is ongoing.
Conclusions:
IT injection of autologous 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. Clinical trial information:
NCT03707808