What does this research mean for the field?

Weekly intratumoral ipilimumab and AS01B combined with bi-weekly low-dose intravenous nivolumab, with or without a single intratumoral injection of myeloid dendritic cells, is safe and produces durable tumor responses in a subset of advanced pretreated melanoma patients. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This trial aims to evaluate the effectiveness of intratumoral autologous myeloid dendritic cells combined with immune checkpoint inhibitors in advanced melanoma patients.

May 30, 2026

A randomized phase II clinical trial on intratumoral autologous CD1c (BDCA-1) + /CD141 (BDCA-3) + myeloid dendritic cells (myDC) plus ipilimumab (IPI) and synthetic adjuvant AS01B combined with low-dose intravenous (IV) nivolumab (NIVO) in advanced pretreated melanoma patients.

Key Points

This trial aims to evaluate the effectiveness of intratumoral autologous myeloid dendritic cells combined with immune checkpoint inhibitors in advanced melanoma patients.
Single-center, prospective, two-stage phase II clinical trial enrolled advanced melanoma patients with injectable metastases.
Patients were randomized 1:1 to receive either myeloid dendritic cells or no myeloid dendritic cells with standard treatment including ipilimumab and nivolumab.
Primary endpoint was the 1-year progression-free survival rate, with secondary endpoints including safety and overall response rate.
In arm A, the overall response rate was 28%, including 2 complete responses; arm B had a 17% overall response rate with 1 complete response.
Median progression-free survival was 14 weeks in arm A and 17 weeks in arm B during a follow-up of 38 weeks.
All patients experienced treatment-related adverse events, with the most common being low-grade fatigue and injection site reactions.

Abstract

e21514 Background: Many advanced melanoma patients (pts) will not obtain a durable response on immune checkpoint- (ICI) and BRAF/MEK-inhibitors (in case of a BRAFV600 mutation). Dendritic cells are crucial for ICI effectiveness and are often excluded from the tumor microenvironment in refractory melanoma. In a previous phase I clinical trial (NCT03707808), low-dose IV NIVO (10 mg) combined with intratumoral (IT) injections of autologous CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC, IPI and synthetic adjuvant AS01B was proven feasible with a promising efficacy signal (DCR 50%) (Tijtgat et al, JITC 2024). We aimed to evaluate the added value of the myDC in a randomized trial. Methods: In this single-center, prospective, two-stage phase II clinical trial, advanced melanoma pts with injectable metastases progressive on standard-of-care life prolonging treatments were randomized 1:1 to receive weekly IT IPI and AS01B with (arm A) or without (arm B) a single IT injection of autologous myDC, and bi-weekly low-dose NIVO IV. At progression (PD), pts in arm B could cross-over to receive the single IT autologous myDC injection with continued study treatment. A sample size of 9 pts in each arm was determined according to a Simon’s two-stage study design. The 1-year PFS rate (1y PFS) served as primary endpoint. Key secondary endpoints were safety, ORR (per RECIST v1.1), PFS and OS. Results: At this interim analysis, 16 pts (8 in each arm) were enrolled (10 male, median (med) age 69, AJCC stage IIIB: 1, IIIC: 5; M1a: 6, M1c: 3, M1d: 1) between Jan ‘24 and DBL (20 Jan '26). There were no significant differences in treatment disposition between both study arms (med 6.5x IT (range 1-22) and 4x IV NIVO (range 1-12)). 13 pts were evaluable for response. The ORR was 28% in arm A (2 CR: 30 wks and 73+ wks), and 17% in arm B (1 CR: 48+ wks). 4 out of 5 pts crossed over at PD to receive myDC. After cross-over, there was one stable disease. After a median follow-up of 38 wks (range 2-101), 11 pts progressed (6 in arm A, 5 in arm B), and 6 had died (4 in arm A, 2 in arm B). Estimation of the 1y PFS is immature, requiring additional follow-up. Med PFS was 14 wks (95% CI 11-16) in arm A and 17 wks (95% CI 11-22) in arm B. All pts experienced at least one treatment-related adverse event (TRAE); most commonly low-grade fatigue (44%) and injection site reaction (56%) with equal frequency in both arms. 5 pts interrupted treatment temporary (4) or definitive (1) due to TRAE. No grade ≥4 TRAE occurred. Conclusions: Weekly IT IPI+AS01B and bi-weekly low-dose NIVO IV, with or without a single IT injection of myDC, is safe and results in durable tumor responses in a meaningful subset of advanced pretreated melanoma pts. Additional follow-up is needed to estimate the added value of IT myDC in this investigational IT immunotherapy regimen. Clinical trial information: EUDRACT 2017-003280-35.

Mark Helpful

Bookmark

Relay