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    Home > Active Ingredient News > Antitumor Therapy > Oncolysis + immunity! Targovax oncos-102 combined with keytruda in the treatment of PD-1 refractory melanoma shows strong efficacy data

    Oncolysis + immunity! Targovax oncos-102 combined with keytruda in the treatment of PD-1 refractory melanoma shows strong efficacy data

    • Last Update: 2019-07-09
    • Source: Internet
    • Author: User
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    July 9, 2019 / BIOON / - targovax ASA is a clinical stage biotechnology company focusing on the development of oncolytic virus for the treatment of refractory solid tumors Recently, the company announced that the evaluation of oncolytic virus oncos-102 (Ad5 / 3-d24-gm-csf) combined with mosadon tumor immunotherapy keytruda (coreda, pabolizumab) for the treatment of PD-1 checkpoint inhibitor (CPI) refractory advanced melanoma has obtained encouraging data The patients included in this study are advanced, unresectable melanoma patients who have progressed after receiving anti-PD-1 CPI treatment, which is a particularly challenging group of patients, with few other treatment options In the first part of the study, nine patients received three intracoronary oncos-102 injections in the first week, followed by keytruda treatment The primary and secondary endpoints of the study were to assess the safety, immune activation, and clinical remission of oncos-102 in combination with keytruda The main scientific purpose is to test the hypothesis that oncos-102 can activate anti-PD-1 resistant patients and react to the re treatment of PD-1 CPI The safety data from Part 1 of the study showed that the continuous oncos-102 and keytruda treatment were well tolerated and the efficacy was very encouraging Of the 9 patients who received the combination therapy of oncos-102 and keytruda, 3 showed clinical remission, including 1 complete remission (CR) and 2 partial remission (PR) The overall remission rate (ORR) was 33% Although the number of patients is small, these results have obvious advantages in this refractory population compared with other exploratory immunotherapy test reports Importantly, these data also confirm the hypothesis that oncos-102 is capable of immunoactivation of drug-resistant tumors in response to an anti-PD-1 CPI re-treatment Oncos-102 was also observed to induce strong innate and adaptive immune activation By the third week, systemic increase of proinflammatory cytokines (IL-6, TNF α and / or IFN γ) was observed in all 9 patients before keytruda treatment, which showed strong systemic immune activation for oncos-102 injection At the tumor level, the infiltration of CD8 + T cells increased in 8 of 9 patients, and the relative level of activated CD8 + T cells (grzb +) increased in 9 patients An increase in T cell infiltration was also observed in lesions without oncos-102 In addition, specific tumor antigens (MAGE-A1 and / or NY-ESO-1) recognized by T cells were found in the blood circulation of 4 patients These data indicate that the initial innate immune activation has successfully transformed into a systemic anti-tumor immune response The second part of the study (Part 2), which is currently recruiting patients, will assess the safety and efficacy of a more intensive treatment regimen (12 intratumoral oncos-102 injections) Oncos-102 is a genetically modified oncolytic adenovirus, which can selectively infect and replicate in cancer cells It has been proved that oncos-102 can activate the immune system to produce tumor specific immune response The mechanism of action is divided into three steps: (1) activating the immune system: oncolytic virus is injected directly into the tumor and cancer cells are infected to release cancer specific antigen; (2) training T cells: APC presents specific antigen in lymph nodes to generate tumor specific T cells; (3) attacking cancer: tumor Specific T cells circulate in the body to identify the lesion and kill cancer cells In phase I clinical studies, oncos-102 can induce both local and systemic innate and adaptive immune activation, which is related to clinical benefits At present, oncos-102 is being developed for the treatment of melanoma, mesothelioma and other refractory tumors "The clinical remission observed in this difficult group of patients with advanced melanoma is very encouraging," said lead researcher Dr Alexander shoushtari of the Sloan Kettering cancer Memorial Center in New York Earlier this year, we decided to expand the scope of the trial to test an enhanced oncos-102 protocol, in order to see if it can produce a deeper and deeper clinical response " Dr Magnus J ü derberg, chief medical officer of targovax, said: "we are pleased that the first part of this study confirms our hypothesis that oncos-102 has the potential to respond to keytruda blocking PD-1 in patients with immune activation checkpoint inhibitor resistance After only three injections of oncos-102, promising clinical remission, including complete remission, was observed, which is rare in this serious patient population Based on our current experience, we speculate that patients will benefit from more oncos-102 injections over a longer period of time, and we will pay close attention to the effect of the second part of the enhanced drug delivery program " Original source: targovax announcements encouragingresults from Part 1 of the oncos-102 and keytruda combination trial in anti-pd1 refinery melanoma
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