Cbl-b-Targeted Cell Therapy Controls Disease in 2 Patients With Solid Tumors
Overall, 6 patients were treated in a feasibility study for a disease control rate of 33.3%.
APN401, an autologous cell therapy that silences Casitas B-lineage lymphoma-b (Cbl-b) in peripheral mononuclear cells (PBMCs), induced stable disease (SD) in 2 patients with advanced, metastatic solid tumors.1
“From a clinical perspective, the therapy of heavily pre-treated recurrent/metastatic HNSCC patients remains a challenge, since the majority of patients show progressive disease and can expect progression-free survival of approximately just 2 months. In this context, disease stabilization for almost 5.5 months in a recurrent/metastatic HNSCC patient treated with APN401 is an encouraging signal and clinically relevant,” investigator professor Thorsten Füreder, MD, program director, respiratory tract cancers and cancer of unknown primary, and chair, immune-oncology tumor board, Medical University of Vienna, said in a statement.2 “Larger trials beyond the case series are now needed to derive a definitive conclusion regarding the clinical activity of this novel approach.”
Data from the case report were reported at the American Associated for Cancer Research (AACR) Annual Meeting 2023, held April 14-19 in Orlando, Florida, by Mario Kuttke, PhD, head, cell therapy, invIOs.
“Taken together, these initial results indicate that APN401, a novel personalized immune cell therapy based on targeted silencing of Cbl-bin PBMCs, may be a safe and effective immunotherapy for solid tumors,” Kuttke and colleagues wrote in their poster.1 "This celltherapy will be further evaluated as a monotherapy along with potential combinations in clinical trials in various solid tumors.”
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Six patients total were treated in a multicenter, open-label, phase 1b feasibility trial (NCT03087591) evaluating 2 increasing dose levels of APN401. The 2 responders in the case study were male, had appendix carcinoma and head and neck squamous cell carcinoma, and were aged 59 and 73 years, and had 11 and 5 prior lines of therapy, respectively. The first responder received 6 cycles of dose level 1 (5x106 PBMCs/kg) followed by 6 cycles of dose level 2 (1.5x107 PBMCs/kg) and the second received 6 cycles of dose level 2.
The 2 responders had SD after treatment with the lowest or intermediate doses of APN401 for a disease control rate of 33.3%. Safety and tolerability data were not presented.
“We believe that our approach based on silencing the master immune system checkpoint Cbl-b could have a significant impact on the development of effective cell therapy treatments for solid tumors and make these cancers vulnerable to anti‑tumor immune responses. These 2 case studies from our successfully completed clinical trial demonstrate APN401’s potential in patients with advanced metastatic disease whose cancer had progressed despite numerous previous treatments,” Romana Gugenberger, PhD, chief medical and scientific officer, inVIOs, added to the statement.2 “In addition, the study confirmed that invIOs’s cell therapy platform represents a feasible approach for rapid local manufacturing of aCbl-b silenced cell therapy, enabling out‑patient treatment with vein-to-vein times of less than 24 hours. The promising results of this study open the door to continuing further development of the APN401 program in earlier lines of treatment, including as a combination therapy.”
