1078MO - MIND-DC: A randomized phase III trial to assess the efficacy of adjuvant dendritic cell vaccination in comparison to placebo in stage IIIB and IIIC melanoma patients

Background

Dendritic cells (DCs) are highly specialized antigen-presenting cells which are essential for the activation of immune responses. Autologous DCs, directly isolated from peripheral blood, loaded with tumor antigens and matured in vitro, can induce tumor-specific immune responses and clinical responses in cancer patients.

Methods

In this phase III clinical trial, patients with resected stage IIIB or IIIC cutaneous melanoma (AJCC 7^th edition) were randomized in a 2:1 ratio to adjuvant treatment with DC vaccination or placebo. The active treatment arm consisted of intranodal injections with autologous CD1c+ myeloid DCs and plasmacytoid DCs loaded with tumor antigens (gp100, tyrosinase, MAGE-C2, MAGE-A3 and NY-ESO-1). When adjuvant treatment with anti-PD1 antibodies became available in the Netherlands in November 2018, accrual was stopped prematurely after inclusion of 151 patients. The primary endpoint is the 2-year recurrence-free survival (RFS) rate. Secondary endpoints include overall survival, immunological response and safety.

Results

In January 2020, we performed a preplanned interim analysis. At that time, 102 patients reached mature data for primary endpoint analysis (recurrence of disease within 2 years of randomisation or at least 2-year follow-up). Thirty-eight percent of patients were female and the median age at start was 55.7 years (range 27-78). At inclusion, 51% of patients had stage IIIB disease and 49% stage IIIC disease. Two-year RFS rate was 21.4% in the treatment arm and 25% in the control arm (HR 1.05; 95% CI: 0.47-3.23), providing no statistically significant evidence of a treatment effect (p=0.67).

Conclusions

Our phase III clinical trial with adjuvant DC vaccination in stage IIIB and IIIC melanoma patients showed no benefit over placebo in terms of 2-year RFS. Correlative analysis of skin-test infiltrating lymphocytes for markers of immunological and clinical response are ongoing.

Clinical trial identification

NCT02993315.

Editorial acknowledgement

Legal entity responsible for the study

Radboud University Medical Centre Nijmegen.

Funding

ZonMw, Ministry of Health, Welfare and Sport (VWS), Miltenyi Biotec (in-kind).

Disclosure

A.A.M. Van der Veldt: Advisory/Consultancy: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Eisai; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Sanofi. J.W.B. de Groot: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Servier. W.R. Gerritsen: Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy: BMS; Advisory/Consultancy: IMS Health; Advisory/Consultancy: IQVIA; Advisory/Consultancy, Research grant/Funding (institution): Janssen-Cilag; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Bayer. All other authors have declared no conflicts of interest.