vididencel (DCP-001)

P1, N=17, Active, not recruiting, University Medical Center Groningen | Recruiting --> Active, not recruiting

P2, N=140, Not yet recruiting, Australian Leukaemia and Lymphoma Group (ALLG)

The locally skin induced immune response leading to influx of a plethora of immune cells, confirmed the mode of action of immune priming through intradermal administration of the cancer vaccine. These results warrant further studies combining vididencel with SOC such as hypomethylating agents in AML maintenance.

Patients who remain in CR after vididencel treatment had highest baseline levels of HLA-DR+ CD45RA+ cells, which could be myeloid cells able to differentiate into dendritic cell subsets, as in general CD45RA+ is lost during maturation from precursor to matured dendritic cells. Vaccination might improve and induce maturation of dendritic cell subsets, such as cDC1, cDC2 and pDC, which enhance antigen capturing, processing and presentation to tumor-reactive T cells, ultimately leading to improved survival.

The observed co-localization of the different immune subsets following vaccination supports the hypothesis of local antigen capturing by blood derived and local antigen presenting cells (Zuo et al, 2021). The local immune response may ultimately leads to a systemic immune response and disease control.

In conclusion, immunotherapy with vididencel is able to induce immune responses in AML patients in CR1 after chemotherapy induction/consolidation, with the number of responses correlating positively with clinicalresponses. Additionally, the vaccine induces a broader immune activation, in both the innate and adaptive immune system, and reduces the number of inhibiting CD8Lag3+ T-cells. This leads to reduction of residual disease in a proportion of patients and promising relapse-free and overall survival.

Taken together, initial data from the phase I trial demonstrate that DCP-001 is safe and well-tolerated and induces durable T-cell responses to tumor associated antigens in OC patients. The study will continue to enroll new patients, follow-up for progression and overall survival and will further analyze the immune responses induced by DCP-001.

Relapse on study was limited, with an estimated RFS at 6 months of 83.7%, which is higher than expected for this MRD+ AML patient population, which would be around 45% as shown for placebo-treated patients from a recent phase III study in a similar patient population (Quazar AML001). Immunotherapy with DCP-001 as AML maintenance therapy is safe and effective in triggering immune responses and converting patients from MRD positive to MRD negative, leading to promising relapse-free survival.

In this phase II study (ADVANCE-II, Clintrials.gov: NCT03697707) AML patients in first complete remission (CR1), with measurable residual disease (MRD), ineligible for HSCT, were treated with an intradermal allogenic leukemia-derived dendritic cell vaccine (DCP-001)...Higher numbers of circulating autologous DC in combination with CD8 effector T-cells, instead of high CD8 CM T-cells might be a prerequisite for successful vaccination to prevent relapse or MRD conversion. Improvement in DC frequencies were observed in patients with stable MRD, which might suggest the potential for more booster vaccinations using this vaccine.

P2, N=20, Active, not recruiting, Mendus | Trial completion date: Dec 2022 --> Dec 2025 | Trial primary completion date: Mar 2022 --> Mar 2023

The data of mean tumor volume (± SEM) 6 weeks after therapy initiation was significantly reduced in the combination group (181.8 ± 29 mm3) as compared to control (522 ± 97.5 mm3), but also vaccination (326.9 ± 54.6 mm3) or drug treatment alone (293.8 ± 29 mm3). Taken together, these preclinical results support the use of DCP-001 as a potential combination therapy with 5-AZA-VEN in AML and related hematological malignancies.

These data suggest that, following intradermal DCP-001 vaccination, local and recruited host APCs capture tumor-associated antigens from the vaccine, become activated and migrate to the draining lymph nodes to subsequently (re)activate tumor-reactive T-cells. The improved uptake of DCP-001 by blocking CD47 rationalizes the possible combination of DCP-001 vaccination with CD47 blocking therapies.

P1, N=17, Recruiting, University Medical Center Groningen | Not yet recruiting --> Recruiting | Trial completion date: Mar 2026 --> Jun 2026 | Initiation date: Mar 2021 --> Jun 2021 | Trial primary completion date: Mar 2025 --> Jun 2025

P2, N=20, Active, not recruiting, DCPrime BV | Recruiting --> Active, not recruiting

Off target effects of drug treatment reduced circulating human immune cells, suggesting optimization of treatment and vaccination scheduling may further enhance the anti-leukemic effect of the combination therapy. These preclinical results support use of DCP-001 as add-on to treatment with AZA-VEN in clinical trials in AML patients.

In both patients multiple antigenic responses after DCP-001 vaccination and high levels of immune cells infiltrates at the injection site were observed. Conclusion DCP-001 used as a relapse vaccine in AML patients, showed recruitment of immune cells to the skin, increased cellular responses to a broad range of tumor associated antigens, and resulted in reversion of the MRD status in some patients.

P1, N=17, Not yet recruiting, University Medical Center Groningen

P2, N=20, Recruiting, DCPrime BV | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2020 --> Mar 2022

The allogeneic leukemia-derived dendritic cell vaccine, DCP-001, has shown in a phase I study to generate both humoral and cellular immune responses and is safe for clinical practice (van de Loosdrecht et al., Cancer Immunol...These patients continue to be in complete remission for at least a year after vaccination. This study continues to enroll patients at a higher vaccine dose of 50.106cells per vaccination and additional data on induced immune responses and MRD status will be shown.