{"id":26912,"date":"2021-03-25T13:35:00","date_gmt":"2021-03-25T13:35:00","guid":{"rendered":"http:\/\/991560130f7b675f6b8a43b61d3f13c1"},"modified":"2024-11-03T15:15:00","modified_gmt":"2024-11-03T15:15:00","slug":"second-drug-targeting-kras-g12c-shows-benefit-in-mutated-non-small-cell-lung-cancer-elcc-2021-virtual-press-release","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/second-drug-targeting-kras-g12c-shows-benefit-in-mutated-non-small-cell-lung-cancer-elcc-2021-virtual-press-release\/","title":{"rendered":"Second Drug Targeting KRAS G12C Shows Benefit in Mutated Non-Small-Cell Lung Cancer [ELCC 2021 Virtual Press Release]"},"content":{"rendered":"<p>99O_PR &#8211; KRYSTAL-1: Activity and Preliminary Pharmacodynamic (PD) Analysis of Adagrasib (MRTX849) in Patients (Pts) With Advanced Non\u2013Small- Cell Lung Cancer (NSCLC) Harboring KRASG12C Mutation<\/p>\n<div id=\"question-idm45812098650640\" readability=\"166\">\n<p>G.J. Riely<sup>1<\/sup>, S-H.I. Ou<sup>2<\/sup>, I. Rybkin<sup>3<\/sup>, A. Spira<sup>4<\/sup>, K. Papadopoulos<sup>5<\/sup>, J.K. Sabari<sup>6<\/sup>, M. Johnson<sup>7<\/sup>, R.S. Heist<sup>8<\/sup>, L. Bazhenova<sup>9<\/sup>, M. Barve<sup>10<\/sup>, J.M. Pacheco<sup>11<\/sup>, K. Velastegui<sup>12<\/sup>, C. Cilliers<sup>12<\/sup>, P. Olson<sup>12<\/sup>, J.G. Christensen<sup>12<\/sup>, T. Kheoh<sup>12<\/sup>, R.C. Chao<sup>12<\/sup>, P.A. J\u00e4nne<sup>13<\/sup><br \/><sup>1<\/sup>Thoracic Oncology Service, Division of Solid Tumor, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA, <sup>2<\/sup>University of California Irvine, Orange, AL, USA, <sup>3<\/sup>Henry Ford Cancer Institute, Henry Ford Hospital, Detroit, USA, <sup>4<\/sup>Research Institute, Virginia Cancer Specialist, Fairfax, USA, <sup>5<\/sup>Clinical Research department, South Texas Accelerated Research Therapeutics (START), San Antonio, TX, USA, <sup>6<\/sup>Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA, <sup>7<\/sup>Lung Cancer Research, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, USA, <sup>8<\/sup>Massachusetts General Hospital, Boston, MA, USA, <sup>9<\/sup>Medicine, Moores Cancer Center &#8211; UC San Diego Health, La Jolla, CA, USA, <sup>10<\/sup>Mary Crowley Cancer Research, Dallas, TX, USA, <sup>11<\/sup>Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA, <sup>12<\/sup>Mirati Therapeutics, Inc., San Diego, CA, USA, <sup>13<\/sup>Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA, USA<\/p>\n<p><strong>Background:<\/strong> KRAS, the most frequently mutated oncogene in cancer, is a key mediator of the RAS\/MAPK signaling cascade that promotes cellular growth and proliferation. KRAS<sup>G12C<\/sup> mutations occur in approximately 14% of NSCLC (adenocarcinoma). Adagrasib, an investigational agent, is a potent, covalent inhibitor of KRAS<sup>G12C<\/sup> that irreversibly and selectively binds to KRAS<sup>G12C<\/sup>, locking it in its inactive state and was optimized for favorable PK properties, including oral bioavailability, long half-life (~24 h), and extensive tissue distribution.<\/p>\n<p><strong>Methods:<\/strong> KRYSTAL-1 (NCT03785249) is a multi-cohort phase I\/II study evaluating adagrasib in pts with advanced or metastatic solid tumors, including NSCLC, harboring a KRAS<sup>G12C<\/sup> mutation previously treated with chemotherapy and an anti-PD-(L)1. Exploratory endpoints include correlative analysis of co-occurring genetic alterations in tumor tissue at baseline and evaluation of the modulation of PD markers, including transcriptomics, in pretreatment and on-study biopsies.<\/p>\n<p><strong>Results:<\/strong> As of 30 August 2020, 79 pts with pretreated NSCLC were treated with adagrasib 600 mg BID (phase I\/Ib and phase II). Most commonly reported (&gt;20%) TRAEs included: nausea (54%), diarrhea (48%), vomiting (34%), fatigue (28%), and increased ALT (23%). Among the 51 pts evaluable for clinical activity, 45% (23\/51) had a partial response (PR) and 26 pts had stable disease (SD). In a subpopulation of pts with STK11-comutations, ORR was 64% (9\/14). Preliminary PD and mechanistic biomarker analyses on pre- and post-treatment tumor NSCLC biopsies (n=3) demonstrate downregulation of KRAS\/MAPK pathway genes including DUSP6 and SPRY4. In pts with tumors harboring STK11-comutations, there was minimal expression of immune transcripts (eg, CD4 and CD8) at baseline and these transcripts were increased after treatment with adagrasib suggesting a potential immune response to therapy.<\/p>\n<p><strong>Conclusions:<\/strong> Adagrasib is tolerable and has demonstrated clinical activity in pts with previously treated KRAS<sup>G12C<\/sup>-mutant NSCLC. Additional PD and mechanistic data will be presented.<\/p>\n<p><strong>Clinical trial identification:<\/strong> NCT03785249<br \/><strong>Editorial acknowledgement:<\/strong> Editorial support was provided by Robin Serody of Axiom Healthcare Strategies.<br \/><strong>Legal entity responsible for the study:<\/strong> Mirati Therapeutics, Inc.<br \/><strong>F<\/strong>unding: Mirati Therapeutics, Inc.<\/p>\n<p><strong>Discolsure:&nbsp;<\/strong>G.J. Riely: Advisory\/Consultancy: Pfizer; Advisory\/Consultancy: Roche; Advisory\/Consultancy: Takeda ; Advisory\/Consultancy: Mirati Therapeutics. S-H.I. Ou: Advisory\/Consultancy: Pfizer; Advisory\/Consultancy: Roche; Advisory\/Consultancy: AstraZeneca; Advisory\/Consultancy: Takeda; Advisory\/Consultancy: TP Therapeutics; Speaker Bureau\/Expert testimony: Genentech; Speaker Bureau\/Expert testimony: AstraZeneca; Speaker Bureau\/Expert testimony: Takeda; Shareholder\/Stockholder\/Stock options: Turning Point Therapeutics.<br \/>I. Rybkin: Advisory\/Consultancy: AstraZeneca. A. Spira: Shareholder\/Stockholder\/Stock options: Lilly; Advisory\/Consultancy: Incyte; Advisory\/Consultancy: Amgen; Advisory\/Consultancy: Novartis; Advisory\/Consultancy: Mirati Therapeutics, Inc; Advisory\/Consultancy: Gritstone ; Advisory\/Consultancy: Jazz Pharmaceuticals; Honoraria (self): CytomX Therapeutics; Honoraria (self): AstraZeneca\/MedImmune; Honoraria (self): Merck; Honoraria (self): Takeda; Honoraria (self): Amgen; Honoraria (self): Janssen Oncology; Honoraria (self): Novartis; Honoraria (self): Bristol Myers Squibb; Honoraria (self): Bayer. K. Papadopoulos: Advisory\/Consultancy: Bayer; Advisory\/Consultancy: ArQule; Advisory\/Consultancy: Basilea. M. Johnson: Spouse\/Financial dependant: Otsuka; Travel\/Accommodation\/Expenses: Abbvie; Travel\/Accommodation\/Expenses: AstraZeneca; Travel\/Accommodation\/Expenses: Genentech; Travel\/Accommodation\/Expenses: Incyte; Travel\/Accommodation\/Expenses: Merck; Travel\/Accommodation\/Expenses: Pfizer; Travel\/Accommodation\/Expenses: Sanofi. R.S. Heist: Advisory\/Consultancy: Boehringer Ingelheim; Advisory\/Consultancy: Novartis; Advisory\/Consultancy: Tarveda; Advisory\/Consultancy: Apollonia; Honoraria (self): Chugai\/Roche. L. Bazhenova: Shareholder\/Stockholder\/Stock options: Epic Sciences; Advisory\/Consultancy, Research grant\/Funding (self): Beyond Spring Pharmaceuticals; Advisory\/Consultancy: AstraZeneca; Advisory\/Consultancy: Takeda; Advisory\/Consultancy: Roche; Advisory\/Consultancy: Blueprint Medicines; Advisory\/Consultancy: G1; Advisory\/Consultancy: Bayer; Advisory\/Consultancy: Boehringer Ingelheim; Advisory\/Consultancy: Novartis; Advisory\/Consultancy: Regeneron; Advisory\/Consultancy: Merck; Advisory\/Consultancy: Johnson &amp; Johnson; Advisory\/Consultancy: BMSi; Advisory\/Consultancy: Daichi Sankyo; Advisory\/Consultancy: Neuvogen. J.M. Pacheco: Advisory\/Consultancy, Travel\/Accommodation\/Expenses: AstraZeneca; Advisory\/Consultancy, Travel\/Accommodation\/Expenses: Novartis; Advisory\/Consultancy: Hengrui; Advisory\/Consultancy: Gerson Lehrman; Advisory\/Consultancy, Travel\/Accommodation\/Expenses: Pfizer; Honoraria (self), Travel\/Accommodation\/Expenses: Takeda. K. Velastegui: Full\/Part-time employment: Mirati Therapeutics, Inc. C. Cilliers: Full\/Part-time employment: Mirati Therapeutics, Inc. P. Olson: Full\/Part-time employment: Mirati Therapeutics, Inc. J.G. Christensen: Leadership role, Shareholder\/Stockholder\/Stock options, Officer\/Board of Directors: Mirati Therapeutics, Inc; Advisory\/Consultancy: BridgeBio; Leadership role, Shareholder\/Stockholder\/Stock options: BCTG Acquisition; Shareholder\/Stockholder\/Stock options: Bluebird Bio. T. Kheoh: Shareholder\/Stockholder\/Stock options, Full\/Part-time employment: Mirati Therapeutics, Inc; Shareholder\/Stockholder\/Stock options: Tocagen. R.C. Chao: Shareholder\/Stockholder\/Stock options, Full\/Part-time employment: Mirati Therapeutics, Inc. P.A. J\u00e4nne: Shareholder\/Stockholder\/Stock options: Gatekeeper Pharmaceuticals; Advisory\/Consultancy, Shareholder\/Stockholder\/Stock options: Loxo; Research grant\/Funding (self): Revolution Medicines; Advisory\/Consultancy, Research grant\/Funding (self): Takeda; Research grant\/Funding (self): Puma Biotechnology; Advisory\/Consultancy, Research grant\/Funding (self): Boehringer Ingelheim; Advisory\/Consultancy, Research grant\/Funding (self): Lilly; Advisory\/Consultancy, Research grant\/Funding (self): Daichi Sankyo; Research grant\/Funding (self): Astellas; Advisory\/Consultancy, Research grant\/Funding (self): AstraZeneca; Advisory\/Consultancy: Pfizer; Advisory\/Consultancy: Merrimack; Advisory\/Consultancy: Roche\/Genentech; Advisory\/Consultancy: Chugai; Advisory\/Consultancy: Mirati Therapeutics, Inc; Advisory\/Consultancy: Araxes; Advisory\/Consultancy: Ignyta; Advisory\/Consultancy: Novartis; Advisory\/Consultancy: Biocartis; Advisory\/Consultancy: Voronoi; Advisory\/Consultancy: SFJ Pharmaceuticals; Advisory\/Consultancy: Silicon Therapeutics. All other authors have declared no conflicts of interest.<\/p>\n<\/div>\n<p><a href=\"http:\/\/www.esmo.org\/newsroom\/press-office\/second-drug-targeting-kras-g12c-shows-benefit-in-mutated-non-small-cell-lung-cancer\">Source<\/a><\/p>","protected":false},"excerpt":{"rendered":"<p>99O_PR &#8211; KRYSTAL-1: Activity and Preliminary Pharmacodynamic (PD) Analysis of Adagrasib (MRTX849) in Patients (Pts) With Advanced Non\u2013Small- Cell Lung Cancer (NSCLC) Harboring KRASG12C Mutation G.J. Riely1, S-H.I. Ou2, I. Rybkin3, A. Spira4, K. Papadopoulos5, J.K. Sabari6, M. Johnson7, R.S. Heist8, L. Bazhenova9, M. Barve10, J.M. Pacheco11, K. Velastegui12, C. Cilliers12, P. Olson12, J.G. Christensen12, [&hellip;]<\/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-26912","post","type-post","status-publish","format-standard","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26912","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=26912"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26912\/revisions"}],"predecessor-version":[{"id":43890,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/26912\/revisions\/43890"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=26912"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=26912"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=26912"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}