Safety and Tolerability of OncoRob © in Patients with Advanced Malignant Solid Tumors under Compassionate Use.

Relevance: OncoRob is a fourth generation bacteriophage-based, highly selective oncolytic Bio-Robot for intravenous systemic administration in cancer patients. It can target, destroy cancer cells and avoid innate and adaptive immune response. In addition, it can distinguish between early and late stage cancer. Purpose: Firstly, to provide treatment to terminally ill patients. Secondly, to test the tolerability, safety, and to find a therapeutic dose of OncoRob after systemic administration in patients with advanced stage III-IV solid tumor malignancies. Thirdly, to evaluate any therapeutic benefit. Material and Methods: All patients received voluntary informed consent to be treated in accordance with the World Medical Association Declaration of Helsinki (WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects, 2013) and the processing of personal data. This treatment protocol was approved by the ethics committee of NZ Proclaimed Hapu “Te Hapu Hoani Haora Hoani O Nu Tireni”. OncoRob was administered to 17 patients in a dose and frequency escalating regimen for an initial period of 6 weeks or 24 doses. Under compassionate use, treatment was continued up to 11 months. The patients were suffering from head & neck, esophageal, skin squamous cell carcinoma (SCC), colorectal, prostate, gastric, melanoma, breast, serous ovarian and clear cell renal carcinoma. OncoRob was administered in escalating doses twice a week, and after reaching the maximum tolerated dose, the patients were treated at that dose four times a week. Clinical lab parameters, vital signs, electrocardiogram and patients own-reported adverse events were used for evaluation of safety. The maximum dose was based on the first sign of any minor toxic side effect likely related to OncoRob. No further concomitant anti-tumor treatment was administered during the study period. All patients were informed about the experimental treatment and signed consent forms. The patients were continuously treated until remission or stable disease was reached. The treatment was stopped after disease progression, non-compliance or upon patient decision. Consequently, the therapeutic effects were evaluated. Results: 17 patients range 48-87 years old received OncoRob starting at a dose of 5x10 ⁹ particles and increasing to the final dose of 5x10 ¹⁰ four times weekly. Total doses of 687 were used. The median treatment period was 4 months and the longest 11 months. During the study period 4 patients contracted COVID-19 and therefore, the treatment needed to be interrupted for two weeks. This interruption caused a worsening of cancer conditions. Treatment-related adverse events were fatigue (26/687), increase or decrease in blood pressure (113/687), increase of body temperature (maximum 38.5C, 8/687), pain on the tumor sites (107/687), shivering (130/687), nausea/vomiting (46/687). These side effects were minor and lasted between 20min and 3 hours. The increase of body temperature occurred 5 hours after the treatments and was observed randomly during the treatment. No patient died during the treatment period and no other events were reported. All clinical lab and vital functions remained unaffected. An increase or stable body weight (16/17) and an improvement of general condition (15/17) could be observed in patients. Reductions of tumor size and tumor markers were observed in 15 out of 17 patients. At the end of the 6 week-treatment period, 2 patients were in total remission, 4 with stable disease, 9 with partial response. The survival rate is 10 out of 17 patients after one-year surveillance. Two patients died within one month after termination of the treatment due to progressive diseases. Conclusions: OncoRob is tolerated without any side effects and dose-limiting toxicities were not observed. Despite extensive prior treatments in some patients, and final stage of disease in 15 out of 17 patients, a positive response or stable disease has been reached during the treatment period. Patients with advanced cancer and large tumor loads should receive more frequent and higher doses under intensive care conditions. Patients in early stage and smaller tumor loads may be treated less intensively.