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

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.

Editorial acknowledgement

Legal entity responsible for the study

Department of Medical Oncology, Universitair Ziekenhuis Brussel.

Funding

Kom op Tegen Kanker (Stand up to Cancer), the Flemish cancer society.

Disclosure

J.K. Schwarze: Non-Financial Interests, Personal, Other: Amgen; Financial Interests, Personal, Invited Speaker: Novartis; Non-Financial Interests, Personal, Other: MSD Oncology. G. Awada: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Non-Financial Interests, Personal, Other: MSD Oncology; Non-Financial Interests, Personal, Other: Astellas Pharma; Non-Financial Interests, Personal, Other: Novartis; Non-Financial Interests, Personal, Other: Pfizer. B. Neyns: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Bristol-Myers Sqibb; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Roche; Financial Interests, Institutional, Funding: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.