Patient With Appendix Carcinoma Shows Stable Disease After Treatment With PBMC Therapy

invIOs’ APN401, an investigational autologous peripheral blood mononuclear cell (PBMC) therapy intended to treat solid tumors, induced stable disease in a patient with appendix carcinoma enrolled in the APN401-103 phase 1b clinical trial, according to case study data presented in a poster exhibited at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting, November 8-12, 2022, in Boston, Massachusetts.^1,2

The patient was administered 6 cycles of APN401 at a dose of 5x10⁶ PBMCs/kg and then 6 cycles of APN401 at a dose of 1.5x10⁷ PBMCs/kg after a 9-week interval. The patient, who had earlier shown progressive disease, maintained stable disease from the time of the first cycle at the low dose until the second cycle of the higher dose. Analysis of biomarkers showed that the patient had elevated IL2 levels and an increased CD8+ to CD4+ ratio after treatment, which first author Romana Gugenberger, PhD, chief medical and scientific officer, invIOs, and colleagues concluded implied potency and cytotoxic efficacy, respectively. Furthermore, stimulation assays revealed elevated levels of IFN-γ, which was defined as a surrogate marker for improved immunity and tumor reactivity. Assessment of the patient’s Eastern Cooperative Oncology Group (ECOG) performance status remained at 0 from screening through the rest of his participation in the trial.

“Our findings highlight that APN401, an autologous cell therapy based on selective Casitas B-lineage lymphoma-b (Cbl-b) silencing, may be a safe, potent, and effective immunotherapy for patients with solid tumors,” Gugenberger and colleagues wrote.¹

The patient is a 59-year-old Caucasian male with high grade mucinous adenocarcinoma of the appendix. He was initially diagnosed in May of 2015 and underwent his first tumor resection at that time, a right hemicolectomy, terminal ileostomy and partial omentectomy, and peritoneal lavage. He underwent a second tumor resection in March of 2019, a subtotal colectomy, lavage, and drainage. He was treated with a total of 11 prior systemic therapy lines before enrollment in the clinical trial, including FLOFOX/bevacizumab, FOLFIRI/panitumumab, FOLFIRI/aflibercept, regorafenib, lonsurf, capecitabine/ bevacizumab, and capecitabine monotherapy. The patient’s concomitant diseases included arterial hypertension and type 2 diabetes.

APN401 consists of a suspension of PBMCs that have been transfected with small interfering RNA, which temporarily reduces expression of Cbl-b without permanent genetic change to the cells, with the intention of restoring immune effector functions against tumor cells.^1,3 This modification is carried out ex vivo with the use of invIOs’ Enhancement Platform for immune Cells (EPiC) technology. The manufacturing process for APN401 can be completed in 3 steps in less than 6 hours.

The open-label APN401-103 trial is evaluating patients with advanced solid tumors at 3 dose levels. It is taking place at multiple trial sites in Austria and is expected to enroll 60 patients. APN401 was previously investigated in 2 earlier phase 1 clinical trials.

“The immune system is the most effective weapon against tumor disease and offers many advantages over conventional therapies such as chemotherapy,” Gugenberger said in a July 2021 statement regarding the launch of the clinical trial.³ “Cbl-b is a master checkpoint in the immune system that controls important processes of the immune response, especially in cancer. APN401, by blocking Cbl-b using RNA interference (RNAi), is designed to reactivate the patient's immune system, allowing it to fight solid tumors. The flexibility of RNAi technology could expand the applicability of cell therapy to additional immune checkpoints and holds enormous potential for new therapeutic approaches.”

REFERENCES

1. Gugenberger R, Dohnal A, Tanzmann A, et al. APN401, a novel EPiC-based anti-cancer cell therapy, case report: Cbl-b silenced, autologous PBMCs induced stable disease in an appendix carcinoma patient. Presented at: Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting November 8-12, 2022; Boston, Massachusetts. Poster 653

2. invIOs presents positive patient data from ongoing Phase 1b trial of APN401 cell therapy in advanced solid tumors at SITC 20223. News release. invIOs GmbH. November 10, 2022. https://www.invios.com/press-release-invios-presents-positive-patient-data-from-ongoing-phase-1b-trial-of-apn401-cell-therapy-in-advanced-solid-tumors-at-sitc-2022/

3. APEIRON Biologics launches next clinical trial with innovative cancer therapy APN401. News release. APEIRON Biologics. July 6, 2021. https://www.apeiron-biologics.com/wp-content/uploads/20210706_APEIRON-Biologics_APN401-study-start_ENG.pdf