Adagrasib (Krazati) as monotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) ENGLISH | DEUTSCH ATOM RSS 1.0 RSS 2.0SIMPLE SEARCHADVANCED SEARCHHELPSERVICESLOGINBrowseTypeSubjectAuthor / EditorInstitutionYear AIHTA - Publications - Search - Adagrasib (Krazati®) as monotherapy for the treatment of advanced non-small cell lung cancer (NSCLC)Rothschedl, E. and Grössmann, N . (2023): Adagrasib (Krazati®) as monotherapy for the treatment of advanced non-small cell lung cancer (NSCLC). Fact Sheet Nr. 159. PDF - Sie müssen einen PDF-Viewer auf Ihrem PC installiert haben wie z. B. GSview, Xpdf oder Adobe Acrobat Reader121kBItem Type: Horizon Scanning of MedicinesSubjects: QV Pharmacology, toxicology, pharmacy > QV 60-370 PharmacologyQZ Pathology > QZ 200-380 Neoplasms.CystsWB
Adagrasib (Krazati) - To treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer Skip to main contentSkip to FDA SearchSkip to footer links An official website of the United States government Here's how you know U.S. Food and Drug Administration Search MenuSearch FDASubmit search Home Drugs Drug Approvals and Databases Drugs@FDADrug Approval Package
Impact of co-mutations and transcriptional signatures in non-small cell lung cancer patients treated with adagrasib in the KRYSTAL-1 trial. KRAS inhibitors are revolutionizing the treatment of NSCLC, but clinico-genomic determinants of treatment efficacy warrant continued exploration. Patients with advanced KRASG12C-mutant NSCLC treated with adagrasib (KRYSTAL-1-NCT03785249) were included to adagrasib (KEAP1: PFS 4.1m vs 9.9m, HR 2.7, p<0.01; OS 5.4m vs 19.0m, HR 3.6, p<0.01; STK11: PFS 4.2m vs 11.0m, HR 2.2, p<0.01; OS 9.8m vs NR, HR 2.6, p<0.01). KEAP1WT/STK11WT status identified adagrasib-treated patients with significantly longer PFS (16.9m) and OS (NR). Pre-clinical analyses further validate the association between KEAP1 loss-of-function and adagrasib resistance. Adagrasib and mTOR
The next-generation KRAS inhibitors…What comes after sotorasib and adagrasib? The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the first driver oncogenes identified in human cancer in the early 1980s. However, it has been deemed 'undruggable' for nearly four decades until the discovery of KRAS G12C covalent inhibitors, which marked a pivotal breakthrough. Currently, sotorasib and adagrasib have been approved by the US FDA to treat patients with non-small cell lung cancer (NSCLC) harboring KRAS G12C mutation. However, their efficacy is somewhat limited compared to that of other targeted therapies owing to intrinsic resistance or early acquisition of resistance. While G12C is the predominant subtype of KRAS mutations in NSCLC, G12D/V is prevalent in colorectal and pancreatic cancers
Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. Adagrasib, an oral small-molecule inhibitor of mutant KRAS G12C protein, has shown clinical activity in pretreated patients with several tumor types, including colorectal cancer. Preclinical studies suggest that combining a KRAS G12C inhibitor with an epidermal growth factor receptor antibody could be an effective clinical strategy. In this phase 1-2, open-label, nonrandomized clinical trial, we assigned heavily pretreated patients with metastatic colorectal cancer with mutant KRAS G12C to receive adagrasib monotherapy (600 mg orally twice daily) or adagrasib (at the same dose) in combination with intravenous cetuximab once a week (with an initial loading dose of 400 mg per square meter of body-surface area
Adagrasib in Non-Small-Cell Lung Cancer Harboring a KRAS(G12C) Mutation. Adagrasib, a KRAS inhibitor, irreversibly and selectively binds KRAS, locking it in its inactive state. Adagrasib showed clinical activity and had an acceptable adverse-event profile in the phase 1-1b part of the KRYSTAL-1 phase 1-2 study. In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily in 52.6% and grade 3 or higher in 44.8% (including two grade 5 events) - and resulted in drug discontinuation in 6.9% of patients. In patients with previously treated -mutated NSCLC, adagrasib showed clinical efficacy without new safety signals. (Funded by Mirati Therapeutics; ClinicalTrials.gov number, NCT03785249.).
Practical Guidance for the Management of Adverse Events in Patients with KRASG12C-Mutated Non-Small Cell Lung Cancer Receiving Adagrasib. Adagrasib (MRTX849) is a KRASG12C inhibitor with favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration. As of September 1, 2022, a total of 853 patients with KRASG12C-mutated solid tumors, including patients with CNS metastases, had received adagrasib (monotherapy or in combination). Adagrasib-related treatment-related adverse events (TRAEs) are generally mild to moderate in severity, start early in treatment, resolve quickly with appropriate intervention, and result in a low rate of treatment discontinuation. Common TRAEs seen in clinical trials included gastrointestinal-related
Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRAS(G12C)-Mutated Non-Small-Cell Lung Cancer Who Have Untreated CNS Metastases. JCO Patients with Kirsten rat sarcoma viral oncogene homolog ()-mutated non-small-cell lung cancer (NSCLC) and untreated CNS metastases have a worse prognosis than similar patients without mutations. Adagrasib has previously demonstrated CNS penetration preclinically and cerebral spinal fluid penetration clinically. We evaluated adagrasib in patients with -mutated NSCLC and untreated CNS metastases from the KRYSTAL-1 trial (ClinicalTrials.gov identifier: NCT03785249; phase Ib cohort), in which adagrasib 600 mg was administered orally, twice daily. Study outcomes included the safety and clinical activity (intracranial [IC
Adagrasib in Advanced Solid Tumors Harboring a KRAS(G12C) Mutation. Adagrasib, a KRAS inhibitor, has demonstrated clinical activity in patients with KRAS-mutated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). KRAS mutations occur rarely in other solid tumor types. We report evaluation of the clinical activity and safety of adagrasib in patients with other solid tumors harboring a KRAS mutation. In this phase II cohort of the KRYSTAL-1 study (NCT03785249; https://www.clinicaltrials.gov/ct2/show/NCT03785249; phase Ib cohort), we evaluated adagrasib (600 mg orally twice daily) in patients with KRAS-mutated advanced solid tumors (excluding NSCLC and CRC). The primary endpoint was objective response rate. Secondary endpoints included duration of response, progression-free survival
Early changes in circulating cell free KRAS G12C predicts response to adagrasib in KRAS mutant non-small cell lung cancer patients. Non-invasive monitoring of circulating tumor DNA (ctDNA) has the potential to be a readily available measure for early prediction of clinical response. Here we report on early ctDNA changes of KRAS G12C in a Phase 2 trial of adagrasib in patients with advanced, KRAS
Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data from Patients with KRASG12C-Mutant Non-Small Cell Lung Cancer. Patients with KRAS-mutant non-small cell lung cancer (NSCLC) with brain metastases (BM) have a poor prognosis. Adagrasib (MRTX849), a potent oral small-molecule KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib has been optimized for favorable pharmacokinetic properties, including long half-life (∼24 hours), extensive tissue distribution, dose-dependent pharmacokinetics, and central nervous system penetration; however, BM-specific antitumor activity of KRASG12C inhibitors remains to be fully characterized. A retrospective database query identified patients with KRAS-mutant NSCLC
First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRAS(G12C) Solid Tumors (KRYSTAL-1). Adagrasib (MRTX849) is an oral, highly selective, small-molecule, covalent inhibitor of KRAS. We report results from a phase I/IB study of adagrasib in non-small-cell lung cancer, colorectal cancer, and other solid tumors harboring the mutation. Patients with advanced -mutant solid tumors were treated with adagrasib 150 mg orally once daily, 300 mg once daily, 600 mg once daily, 1,200 mg once daily, or 600 mg orally twice a day using an accelerated titration design, which transitioned to a modified toxicity probability interval design when a predefined degree of toxicity was observed or target adagrasib exposure was achieved. Safety, pharmacokinetics
KRAS Secondary Mutations That Confer Acquired Resistance to KRAS G12C Inhibitors, Sotorasib and Adagrasib, and Overcoming Strategies: Insights From In Vitro Experiments. KRAS mutations have been recognized as undruggable for many years. Recently, novel KRAS G12C inhibitors, such as sotorasib and adagrasib, are being developed in clinical trials and have revealed promising results in metastatic NSCLC. Nevertheless, it is strongly anticipated that acquired resistance will limit their clinical use. In this study, we developed in vitro models of the KRAS G12C cancer, derived from resistant clones against sotorasib and adagrasib, and searched for secondary KRAS mutations as on-target resistance mechanisms to develop possible strategies to overcome such resistance. We chronically exposed Ba/F3
A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4) This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus
Bioequivalence Study Between Adagrasib Reference Tablets and High Drug Load Tablets This is a study to evaluate bioequivalence between adagrasib reference tablets and high drug load tablets in healthy adult participants.
A Study Evaluating the Efficacy and Safety of Divarasib Versus Sotorasib or Adagrasib in Participants With Previously Treated KRAS G12C-positive Advanced or Metastatic Non-Small Cell Lung Cancer The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C
A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations To learn if the drug combination of adagrasib, cetuximab, and cemiplimab can help to control metastatic CRC with KRAS G12C mutations. Primary Objective • To determine the objective response rate of the adagrasib, cetuximab, and cemiplimab combination for treatment of advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy. Secondary Objectives * To estimate duration of response (DOR), progression free survival (PFS), and overall survival (OS) for the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy
Adagrasib + SRS for Patients With Metastatic KRAS G12C-mutated NSCLC With Untreated Brain Metastases This is a single arm phase 2 trial is to evaluate the efficacy of SRS plus adagrasib for the treatment of brain metastases for patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC). A total of 30 patients will be enrolled on this study. undefined
Phase Ib Trial of the KRAS G12C Inhibitor Adagrasib (MRTX849) in Combination With the PARP Inhibitor Olaparib in Patients With KRAS G12C Mutated Advanced Solid Tumors, With a Focus on Gynecological, Breast, Pancreatic and KEAP1 Mutated Non-small Cell Lun Find the recommended dose of the investigational drug combination of adagrasib and olaparib that can be given to participants with advanced solid tumor(s) with a KRAS G12C and/or KEAP1 mutation. Primary ObjectivesTo evaluate the safety and tolerability of adagrasib in combination with olaparib in participants with KRAS G12C mutant advanced solid tumors.To establish the maximum tolerated dose and/or recommended phase 2 dose (MTD/RP2D) of the combination in participants with KRAS G12C mutant advanced solid tumors.Secondary ObjectivesTo
A PK Study to Assess the Drug-drug Interaction of a BCRP Inhibitor on Adagrasib A Phase 1, Open-label, One-sequence Crossover Study to Investigate the Effect of a Breast Cancer Resistance Protein Inhibitor on the Single-dose Pharmacokinetics of Adagrasib in Healthy Adult Subjects undefined