{"id":26817,"date":"2021-03-01T17:30:00","date_gmt":"2021-03-01T17:30:00","guid":{"rendered":"http:\/\/4255441a52d25ee9713d9ccb1fd22d42"},"modified":"2024-11-03T15:15:45","modified_gmt":"2024-11-03T15:15:45","slug":"encouraging-early-results-seen-with-novel-medi1191-in-advanced-tumours","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/encouraging-early-results-seen-with-novel-medi1191-in-advanced-tumours\/","title":{"rendered":"Encouraging Early Results Seen with Novel MEDI1191 in Advanced Tumours"},"content":{"rendered":"

Early results from a phase I study showed promising safety, tolerability, and efficacy following sequential intratumoural (IT) administration of MEDI1191, an IL-12 mRNA agent, followed by durvalumab (anti-PD-L1) in patients with advanced solid tumours who progressed on one or more lines of standard systemic treatment. These findings were reported at the ESMO Targeted Anticancer Therapies (TAT) Virtual Congress 2021<\/a> held on 1-2 March.<\/strong><\/p>\n

Dr. Omid Hamid, head of Translational Research and ImmunoOncology at The Angeles Clinical and Research Institute, a Cedars-Sinai Affiliate in Los Angeles, USA explained that IL-12 is a strong driver of the TH1 immune response. Systemically delivered recombinant IL-12 is poorly tolerated.  <\/p>\n

MEDI1191 is a lipid nanoparticle-formulated therapy that was developed to be administered by IT injection in order to drive local IL-12 production and induce anti-tumour activity.<\/p>\n

Data from preclinical models showed that IT IL-12 mRNA induced a potent TH1-mediated anti-tumour response, which could be further enhanced by PD-L1 blockade.<\/p>\n

Dr. Hamid and co-investigators evaluated the safety and efficacy of MEDI1191 (IL-12 mRNA) in a phase I, multicentre, open-label, dose-escalation and expansion study (NCT03946800).<\/p>\n

The dose escalation part 1 of this study aimed to determine the dose of MEDI1191 in combination with durvalumab at 1500 mg intravenously that was delivered every 4 weeks either sequentially or concurrently in patients with advanced solid tumours that included both superficial and deep-seated lesions. The study included patients who were immunotherapy-na\u00efve or pre-treated, including anti-PD-1(L) and CTLA-4 pretreated solid tumours.<\/p>\n

The primary endpoints for part 1 included safety and the determination of the maximum tolerated dose (MTD) as well as a pharmacodynamic active dose, and the secondary endpoints were efficacy according to the disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS), overall survival (OS), pharmacokinetics, and immunogenicity. The study also includes an expansion part 2.<\/p>\n

From May 2019 to December 2020, the study enrolled 10 patients with superficial lesions who were relegated to one of three dose escalation cohorts. Of these, 6 patients had received prior immunotherapy.<\/p>\n

Preliminary analysis indicates MEDI1191 is safe<\/h4>\n

Regarding the co-primary endpoint of safety, no dose limiting toxicities, adverse events of special interest, treatment related adverse events \u2265 Grade 3, or treatment-related serious adverse events were reported.<\/p>\n

In the efficacy analysis, two partial responses (PRs) were demonstrated in patients that had received prior immunotherapy and also had PD-L1 negative tumours. Of these PRs, one occurred in a patient with mucosal melanoma who displayed tumour shrinkage of both injected and non-injected lesions following 2 doses of MEDI1191 that occurred prior to administration of sequential durvalumab. This patient was PD-1 and CTLA-4 pretreated with progression on those regimens. Another patient with PD-1 pretreated HNSCC showed response to therapy.<\/p>\n

Preliminary findings from the pharmacodynamic analysis indicated that MEDI1191 induced transient elevation of serum levels of IL-12, as well as concordant changes in IFN-gamma and CXCL10.<\/p>\n

Conclusions<\/h4>\n

Based on these data the authors concluded that the IT MEDI1191 sequentially delivered with durvalumab was well-tolerated and showed encouraging efficacy.<\/p>\n

The treatment also demonstrated preliminary anti-tumour and pharmacodynamic activity in immunotherapy pre-treated patients that was consistent with the expected mechanism of action. However, they advised that these preliminary data require further validation.<\/p>\n

They noted that this study is active and recruiting. Current regimes will evaluate concurrent administration of MEDI1191 and durvalamab in cutaneous\/subcutaneous lesions and in virsceral metastases.<\/p>\n

This study was funded by AstraZeneca.<\/p>\n

Reference<\/h4>\n

19O \u2013 Hamid O, Hellman M, Carneiro B, et al.<\/em> Preliminary safety, antitumor activity and pharmacodynamics results of HIT-IT MEDI1191 (mRNA IL-12) in patients with advanced solid tumors and superficial lesions. ESMO Targeted Anticancer Therapies (TAT) Virtual Congress (1-2 March 2021)<\/a>.<\/p>\n

Source<\/a><\/p>","protected":false},"excerpt":{"rendered":"

Early results from a phase I study showed promising safety, tolerability, and efficacy following sequential intratumoural (IT) administration of MEDI1191, an IL-12 mRNA agent, followed by durvalumab (anti-PD-L1) in patients with advanced solid tumours who progressed on one or more lines of standard systemic treatment. These findings were reported at the ESMO Targeted Anticancer Therapies […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-26817","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26817","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=26817"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26817\/revisions"}],"predecessor-version":[{"id":45395,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26817\/revisions\/45395"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=26817"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=26817"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=26817"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}