KEY TAKEAWAYS
- The phase 1 (myDAvIpNi) first-in-human clinical trial assessed the response of intratumoral injection of CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC in combination with repeated IT administration of ipilimumab and AS01B and systemic low dose nivolumab in pts with refractory advanced melanoma.
- Out of the eight enrolled patients, six were evaluable for response, with two achieving durable CRs, and one obtaining a PR.
- The treatment showed promising clinical results with no safety issues, meriting further investigation.
The study enrolled patients (pts) with metastatic melanoma refractory to ICB and BRAF/MEK inhibitors. Researchers collected patients’ white blood cells through leukapheresis to isolate CD1c (BDCA-1)+ and 23 (BDCA-3)+ myDC. Pts were given a low dose of intravenous nivolumab (10mg, q2w) and IT administration of ipilimumab (10mg, q2w) and AS01B (50μg, q2w) for up to one year. In addition, isolated myDC was administered (clinical or ultrasound-guided) as a single injection into a metastatic lesion on day 2. To ensure the safety and feasibility of the treatment, baseline, and on-treatment core-needle biopsies were taken for analysis of immune cell markers using multiplex immunohistochemistry (mIHC).
The study enrolled eight pts who all received treatment without experiencing any unexpected adverse events. Out of the six pts who were evaluated for response, two of them achieved a durable CR that has been ongoing for 12 and 9 months after the initiation of study therapy. Additionally, another patient obtained a PR, which has also been ongoing for 9 months. One patient had an SD as their best objective response, and the treatment is continuing for two pts. Preliminary mIHC analyses comparing baseline with on-treatment biopsies demonstrated a rise in tumor-infiltrating lymphocytes and a decrease in the mean distance between SOX10+ tumor cells and CD8+ T cells in a responding patient.
The study found that the intratumoral injection of CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC, along with repeated IT administration of ipilimumab and AS01B, as well as systemic low-dose nivolumab, produced promising clinical results. The researchers did not observe any unexpected safety issues, which suggests that this treatment combination warrants further investigation.
Source: https://eado2023.com/wp-content/uploads/2023/04/Abstract-Band_EADO2023_Stand-21-04-2023-kl.pdf
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03707808
Dr Jens Tijtgat1, Anais Boisson2, Dr Manon Vounckx1, Dr Iris Dirven1, Prof Dr Steven Raeymaeckers3, Prof Ivan Van Riet4, Latoya Stevens1, Xenia Geeraerts1, Prof Sandra Tuyaerts1, Prof Karen Willard-Gallo2, Prof Dr Bart Neyns1 1 Department of Medical Oncology/Laboratory of Medical and Molecular Oncology (LMMO), Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium / 2 Laboratoire d’oncologie et de chirurgie expérimentale(LOCE) and Molecular Immunology Unit (MIU) – Université Libre de Bruxelles, Brussels, Belgium / 3 Department of Radiology, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium / 4 Department of Hematology, Stem cell laboratory, Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium
