TY - JOUR
T1 - Abstract 962MO. A phase I clinical trial on intratumoral injection of autologous CD1C (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells (myDC) in combination with talimogene laherparepvec (T-VEC) in patients with advanced pretreated melanoma
AU - Schwarze, Julia Katharina
AU - Tijtgat, Jens
AU - Awada, Gil
AU - Cras, Louise
AU - Dufait, Inès
AU - Forsyth, Ramses
AU - Van Riet, Ivan
AU - Tuyaerts, Sandra
AU - Neyns, Bart
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Background Intratumoral (IT) myDC play a pivotal role in initiating antitumor immune responses within the tumor microenvironment. IT injection of the oncolytic virus T-VEC may lead to the release of tumor antigens and maturation signals that can be captured and processed by CD1c (BDCA-1)+/CD141 (BDCA-3)+ myDC, thereby reinvigorating the cancer immunity cycle. Methods Patients (pts) with ICI-refractory melanoma received IT injections of ≥1 non-visceral metastases with T-VEC (106 PFU/mL; max 4 mL) on day 1 followed by IT injection of CD1c (BDCA-1)+ (cohort C1) or CD1c (BDCA-1)+/CD141 (BDCA-3)+ myDC (cohort C2) on day 2. Injection of T-VEC (108PFU/mL; max 4 mL) was repeated on day 21, and Q2w thereafter. In C1, the number of CD1c (BDCA-1)+myDCs was escalated from 0.5x106, to 1x106, and 10x106 cells. In C2, pts received all isolated CD1c (BDCA-1)+/CD141 (BDCA-3)+ myDCs. Primary objectives were safety and feasibility. Immunohistochemistry (IHC), gene expression profiling (GEP), and multiplexed immunofluorescence (mIF) of baseline and on-treatment biopsies was performed. Results 13 pts were enrolled (C1: n=7 [respectively 2, 2, and 3 pts per dose-level of myDC]; C2: n=6). Pts received the predefined dose of myDCs and a median of 6 (range 3-8) T-VEC injections. Most frequent AEs were fatigue in 11 pts (85%), injection-site pain in 9 pts (69%), fever in 8 pts (62%), and chills and flu-like symptoms in 6 pts (46%). There were no G4 or G5 AEs. AEs of special interest were a G3 eosinophilia and a G2 purpuric rash at the injection-site; 2 pts (C1, dose level 3) developed a pathological complete remission that is ongoing at 24 months following treatment initiation. One pt in C2 had an unconfirmed partial response (iRECIST); a mixed response was observed in 2 pts. Responses were observed in both injected and non-injected lesions. In responder pts, infiltration of lymphocytes was observed on IHC. GEP and mIF on biopsies are ongoing. Conclusions IT co-injection of CD1c (BDCA-1)+ +/- CD141 (BDCA-3)+ myDC plus T-VEC is feasible, tolerable, and resulted in encouraging early signs of durable antitumor activity in pts with ICI-refractory melanoma. Clinical trial identification NCT03747744
AB - Background Intratumoral (IT) myDC play a pivotal role in initiating antitumor immune responses within the tumor microenvironment. IT injection of the oncolytic virus T-VEC may lead to the release of tumor antigens and maturation signals that can be captured and processed by CD1c (BDCA-1)+/CD141 (BDCA-3)+ myDC, thereby reinvigorating the cancer immunity cycle. Methods Patients (pts) with ICI-refractory melanoma received IT injections of ≥1 non-visceral metastases with T-VEC (106 PFU/mL; max 4 mL) on day 1 followed by IT injection of CD1c (BDCA-1)+ (cohort C1) or CD1c (BDCA-1)+/CD141 (BDCA-3)+ myDC (cohort C2) on day 2. Injection of T-VEC (108PFU/mL; max 4 mL) was repeated on day 21, and Q2w thereafter. In C1, the number of CD1c (BDCA-1)+myDCs was escalated from 0.5x106, to 1x106, and 10x106 cells. In C2, pts received all isolated CD1c (BDCA-1)+/CD141 (BDCA-3)+ myDCs. Primary objectives were safety and feasibility. Immunohistochemistry (IHC), gene expression profiling (GEP), and multiplexed immunofluorescence (mIF) of baseline and on-treatment biopsies was performed. Results 13 pts were enrolled (C1: n=7 [respectively 2, 2, and 3 pts per dose-level of myDC]; C2: n=6). Pts received the predefined dose of myDCs and a median of 6 (range 3-8) T-VEC injections. Most frequent AEs were fatigue in 11 pts (85%), injection-site pain in 9 pts (69%), fever in 8 pts (62%), and chills and flu-like symptoms in 6 pts (46%). There were no G4 or G5 AEs. AEs of special interest were a G3 eosinophilia and a G2 purpuric rash at the injection-site; 2 pts (C1, dose level 3) developed a pathological complete remission that is ongoing at 24 months following treatment initiation. One pt in C2 had an unconfirmed partial response (iRECIST); a mixed response was observed in 2 pts. Responses were observed in both injected and non-injected lesions. In responder pts, infiltration of lymphocytes was observed on IHC. GEP and mIF on biopsies are ongoing. Conclusions IT co-injection of CD1c (BDCA-1)+ +/- CD141 (BDCA-3)+ myDC plus T-VEC is feasible, tolerable, and resulted in encouraging early signs of durable antitumor activity in pts with ICI-refractory melanoma. Clinical trial identification NCT03747744
U2 - 10.1016/j.annonc.2021.08.1347
DO - 10.1016/j.annonc.2021.08.1347
M3 - Meeting abstract (Journal)
VL - 32
SP - S832-S833
JO - Annals of Oncology
JF - Annals of Oncology
SN - 0923-7534
T2 - ESMO CONGRES
Y2 - 16 September 2021 through 21 September 2021
ER -