1086P - Intratumoral (IT) administration of autologous CD1c(BDCA-1)+/CD141(BDCA-3)+myeloid dendritic cells (myDC) with the immunologic adjuvant AS01B plus ipilimumab (IPI) and IV nivolumab (NIVO) in patients with refractory advanced melanoma: A phase Ib clinical trial

Background

Advanced melanoma patients (pts), who progress on immune checkpoint blockade (ICB) or targeted therapy (for BRAF ^mut) have a poor outcome. Conventional CD1c (BDCA-1)⁺ and CD141 (BDCA-3)⁺ myDC in the tumor microenvironment are crucial for eliciting antitumor immune responses and the effectiveness of PD-1/CTLA-4 ICB. Following a single IT injection of autologous myDC with (repeated Q2w thereafter) the synthetic saponin-based immune adjuvant AS01_B and IPI plus IV NIVO, 3 responses were obtained in 8 refractory melanoma pts (ClinicalTrials.gov Identifier: NCT03707808 ; J. Tijtgat et al. JITC 2024).

Methods

In a second cohort of this phase Ib trial the safety of a weekly dose-intensified regimen of IT 10 mg IPI and 50 μg AS01_B, plus 10 mg NIVO IV Q2w was investigated. As previously, autologous blood myDC isolated by leukapheresis, were injected into the same lesion (day 2). Baseline and on-treatment biopsies were collected.

Results

Six pts (3 M, med age 55y [35-60]) with unresectable stage IIIC (n=2), stage IV-M1a (n=3), and -M1c (n=1) received the planned study treatment with a median of 5 IT and 6 IV injections. Two pts obtained a complete response (CR), and 1 pt a stable disease (disease control rate 50%). A pathological CR was documented in 3 out of 10 injected lesions (in 2 pts with “overall” 1 CR, and 1 SD). mPFS was 35w, mOS was not reached. Treatment related adverse events (TRAE) included transient grade 1/2 injection site reactions and constitutional symptoms. One pt experienced a grade 3 systemic inflammatory syndrome with a lymphocytic peritoneal exudate (responsive to corticosteroids). There were no grade 4-5 TRAE. Multiplex IHC analysis of tumor biopsies is ongoing.

Conclusions

The combination of IT CD1c (BDCA-1)⁺/CD141 (BDCA-3)⁺ DC-injection, with weekly IT IPI and AS01_B, plus low-dose IV NIVO is tolerable and demonstrated clinically meaningful anti-tumor activity in refractory advanced melanoma. The weekly administration regimen is considered the maximum tolerated treatment intensity. The trial continues as a randomized phase II trial.

Clinical trial identification

NCT03707808; April 2023.

Editorial acknowledgement

Legal entity responsible for the study

B. Neyns.

Funding

Kom op tegen Kanker.

Disclosure

All authors have declared no conflicts of interest.