{"id":46727,"date":"2024-08-05T07:00:00","date_gmt":"2024-08-05T07:00:00","guid":{"rendered":"http:\/\/39b68d72b2f814340eb1670d86c6cfe4"},"modified":"2024-11-03T15:11:48","modified_gmt":"2024-11-03T15:11:48","slug":"telisotuzumab-vedotin-associated-with-durable-responses-in-c-met-protein-overexpressing-non-squamous-egfr-wild-type-nsclc-and-enriched-orrs-in-patients-with-high-c-met-expression","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/telisotuzumab-vedotin-associated-with-durable-responses-in-c-met-protein-overexpressing-non-squamous-egfr-wild-type-nsclc-and-enriched-orrs-in-patients-with-high-c-met-expression\/","title":{"rendered":"Telisotuzumab Vedotin Associated with Durable Responses in c-Met Protein\u2013Overexpressing Non-Squamous EGFR-wild-type NSCLC and Enriched ORRs in Patients with High c-Met Expression"},"content":{"rendered":"

A phase II LUMINOSITY study aimed to determine which patients with c-Met protein\u2013overexpressing non-small cell lung cancer (NSCLC) would most benefit from treatment with telisotuzumab vedotin. The non-squamous EGFR<\/em>-wild-type NSCLC cohort met criteria for expansion, while the squamous and non-squamous EGFR<\/em>-mutated cohorts met protocol-specified criteria for futility. The highest overall response rate (ORR) was observed among patients with c-Met protein\u2013overexpressing, non-squamous EGFR<\/em>-wild-type NSCLC, and ORR was enriched among patients with c-Met high overexpressing tumours.<\/p>\n

Although ORR was increased in the c-Met\u2013high population, disease control rate, progression-free survival (PFS), and overall survival (OS) were comparable between c-Met high, c-Met intermediate, and c-Met total overexpression, indicating telisotuzumab vedotin was efficacious in patients with c-Met\u2013overexpressing tumours regardless of the level of expression. The findings are reported by Dr. D Ross Camidge of the University of Colorado Cancer Center in Aurora, Colorado, US and colleagues on 6 June 2024 in the JCO<\/em>.<\/p>\n

Aside from any role in acquired resistance to targeted therapies, primary MET <\/em>gene dysregulation can occur through amplification or mutation in approximately 5% and around 2-4% of patients with NSCLC. c-Met tyrosine kinase inhibitors have been successfully developed for patients with MET <\/em>exon 14 skipping mutations and are in development for MET <\/em>amplification.<\/p>\n

Approximately 25-39% of patients with NSCLC have tumours that overexpress the c-Met protein, which may co-exist with MET <\/em>genomic alterations. Overexpression prevalence is around 25% in patients with non-squamous EGFR<\/em>-wild-type NSCLC. c-Met protein overexpression is a negative prognostic factor for survival in early and advanced NSCLC.<\/p>\n

The authors wrote in the background that although numerous clinical trials are evaluating targeted therapies against cancers with MET <\/em>genomic alterations, there are currently no therapies available to specifically target c-Met protein overexpression. Telisotuzumab vedotin is a first-in-class c-Met\u2013directed antibody-drug conjugate using c-Met protein overexpression as a biomarker to target the cytotoxic payload to tumour cells. It has shown promising activity and an acceptable safety profile in patients with c-Met protein\u2013overexpressing NSCLC in a phase I study.<\/p>\n

The phase II LUMINOSITY study evaluated efficacy and safety of telisotuzumab vedotin in patients with c-Met protein\u2013overexpressing locally advanced\/metastatic NSCLC with aim to identify the population best suited for treatment with telisotuzumab vedotin in the second- or third-line (stage 1), and further assess efficacy and safety in the selected population (stage 2). The c-Met protein\u2013overexpressing, non-squamous EGFR<\/em>-wild-type NSCLC population was selected for further evaluation in stage 2. The study team reports findings from primary efficacy and safety analyses.<\/p>\n

Eligible patients had locally advanced\/metastatic c-Met protein\u2013overexpressing NSCLC and at least two prior lines of therapy, including at least one line of systemic chemotherapy. c-Met protein overexpression in non-squamous EGFR<\/em>-wild-type NSCLC was defined as \u226525% tumour cells with 3+ staining, defined as high in case \u226550% 3+, intermediate \u226525%\u2013<50%. Primary endpoint was ORR by independent central review.<\/p>\n

In total, 172 patients with non-squamous EGFR<\/em>-wild-type NSCLC received telisotuzumab vedotin in stages 1 and 2; ORR was 28.6% (95% confidence interval [CI] 21.7\u201336.2); in c-Met high 34.6% (95% CI 24.2\u201346.2); in c-Met intermediate 22.9% (95% CI 14.4\u201333.4). Median duration of response was 8.3 months (95% CI 5.6\u201311.3); in c-Met high 9.0 (95% CI 4.2\u201313.0); in c-Met intermediate 7.2 (95% CI 5.3\u201311.5). Median OS was 14.5 months (95% CI 9.9\u201316.6); in c-Met high 14.6 (95% CI 9.2\u201325.6); in c-Met intermediate 14.2 (95% CI 9.6\u201316.6). Median PFS was 5.7 months (95% CI 4.6\u20136.9); in c-Met high 5.5 (95% CI 4.1\u20138.3); in c-Met intermediate 6.0 (95% CI 4.5\u20138.1).<\/p>\n

Most common any-grade treatment-related adverse events were peripheral sensory neuropathy (30%), peripheral oedema (16%), and fatigue (14%); the most common grade \u22653 was peripheral sensory neuropathy (7%).<\/p>\n

The authors commented that this phase II study is limited by the lack of a comparator arm. The ongoing global, randomised phase III TeliMET NSCLC-01 study compares telisotuzumab vedotin monotherapy with docetaxel in patients with previously treated locally advanced\/metastatic, c-Met protein\u2013overexpressing, non-squamous EGFR<\/em>-wild-type NSCLC. Given the potential overlap of some genomic markers of MET <\/em>activation with c-Met protein overexpression, retrospective analyses of the current study data on available tissue or blood for these markers will be of interest.<\/p>\n

The study was funded by AbbVie.<\/p>\n

Reference<\/h3>\n

Camidge DR, Bar J, Horinouchi H, et al.<\/em> Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein\u2013 overexpressing advanced non-squamous EGFR-wildtype NSCLC in the Phase 2 LUMINOSITY trial<\/a>. JCO<\/em>; Published online 6 June 2024. DOI: 10.1200\/JCO.24.00720<\/p>\n

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

A phase II LUMINOSITY study aimed to determine which patients with c-Met protein\u2013overexpressing non-small cell lung cancer (NSCLC) would most benefit from treatment with telisotuzumab vedotin. The non-squamous EGFR-wild-type NSCLC cohort met criteria for expansion, while the squamous and non-squamous EGFR-mutated cohorts met protocol-specified criteria for futility. The highest overall response rate (ORR) was observed […]<\/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-46727","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46727","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=46727"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46727\/revisions"}],"predecessor-version":[{"id":46952,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/46727\/revisions\/46952"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=46727"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=46727"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=46727"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}