Sotorasib kras g12c. In addition, Briere et al.

Sotorasib kras g12c Sotorasib is the first KRAS G12C inhibitor to show statistically significant improvement in progression-free survival compared with standard-of-care docetaxel, with a 34% decrease in the relative risk of disease Sotorasib is a small molecule that selectively and irreversibly targets KRAS G12C. Adagrasib and sotorasib, two FDA-approved agents specifically targeting this mutation, have shown promise in clinical trials. using the same model demonstrated a switch in the tumor microenvironment (TME) from Given that sotorasib and adagrasib are the only KRAS G12C inhibitors currently approved for clinical use, there is an urgent need to discover new KRAS mutation-targeted agents. However The most common mutation, KRAS G12C, is present in 13% of lung adenocarcinomas. 5. G12C-mutated locally advanced or metastatic NSCLC who received at least one prior Background: The KRAS G12C mutation, prevalent in various malignancies, including non-small cell lung cancer (NSCLC), represents a unique therapeutic target. Antibody-based therapies have emerged as a powerful strategy for the management of diverse cancers. Sotorasib is a novel KRAS G12C inhibitor that has shown promising results in preclinical and clinical studies, granting its conditional approval by the FDA in May 2021. The approval was based on CodeBreaK Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring KRAS glycine-to-cysteine amino acid substitutions at codon 12 (KRAS G12C). It remains Sotorasib (LUMAKRAS™ in the USA and LUMYKRAS™ in the EU) is an orally active, first-in-class G12C-mutant KRAS (KRASG12C) inhibitor. Sotorasib 960 mg has Abstract. G12C single-nucleotide variant (KRAS G12C) is the most frequently reported in NSCLC patients, with a prevalence of about 12–13 %. showed that T cell presence was essential for durable responses in subcutaneous tumors of the colon cancer model CT26 treated with sotorasib. For many “Amgen’s Investigational KRAS G12C Inhibitor Sotorasib Demonstrated Rapid, Deep and Durable Responses in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer” Amgen Press Whilst sotorasib and adagrasib are currently approved for use in the second-line setting and beyond for patients with advanced/metastatic NSCLC, testing and reporting of the KRAS G12C variant should be included in routine biomarker testing prior to first-line therapy. [7] [8] Sotorasib is an inhibitor of the RAS GTPase family. Sotorasib showed activity (tumor shrinkage) in patients with non-small cell lung cancer harboring this specific mutation, and efficacy was tested in the CodeBreaK 200, open-label KRAS p. By binding irreversibly to KRASG12C, sotorasib inhibits downstream signalling pathways which are associated with cell growth and differentiation. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients of higher risk. The approval was bas Sotorasib in KRAS. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials. This study aims to compare their efficacy in treating KRAS G12C-mutated Patients with KRAS G12C –mutated locally advanced or metastatic NSCLC have an actionable mutation and may be eligible for LUMAKRAS ® (sotorasib) following first line of therapy 1. This study aims to compare their efficacy in treating KRAS G12C-mutated To test combinational therapy, we first tested three KRAS-G12C mutant cell lines: H358 a sotorasib sensitive; SW1573, a sotorasib-resistant and a novel patient-derived cell line, PF139. G12C-mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer Sotorasib is a small-molecule Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C inhibitor indicated for the treatment of KRAS G12C-driven cancers. Preclinical studies in 22 cell lines and xenograft models demonstrated that sotorasib does not inhibit KRAS wild type or non–KRAS G12C lines/tumors. Preliminary results from the phase I and II sotorasib trials showed promise in terms of RR and DOR . Last reviewed: 30 March 2022 Next review: More evidence on sotorasib is being collected. The safety and efficacy of sotorasib, a KRAS G12C inhibitor, in previously treated patients with KRAS p. G12C-Mutated Advanced Pancreatic Cancer. G12C mutation. Combining the KRAS G12C inhibitor sotorasib with panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, In this real-world multicenter study of more than 160 patients with metastatic KRAS G12C-mutated NSCLC, sotorasib demonstrated promising efficacy with an ORR of 39% and a median OS of 9. The KRAS G12C mutation occurs in approximately 13% of non-small cell lung cancer (NSCLC) and 1% to 3% of colorectal cancer and other solid cancers. The most common mutation subtype, KRAS G12C, occurs in 13% of lung adenocarcinomas. Yaeger R, Weiss J, Pelster MS, et al. CodeBreaK 200. Although (R)-9 proved to be an exceptionally potent inhibitor of KRAS G12C signaling (p-ERK IC 50 = 0. Because amino acid sequences of the three main RAS isoforms—KRAS, NRAS, and HRAS—are highly similar, we hypothesized that some KRAS G12C inhibitors Furthermore, adagrasib phenocopies the combination effect of sotorasib and CFZ by suppressing KRAS activity and inhibiting cell cycle progression in inherently resistant cells. Methods: A retrospective pharmacovigilance was conducted to examine adverse events (AEs) Sotorasib is a type of targeted therapy. The trial consisted of dose escalation and expansion Monotherapy with KRAS G12C inhibitors has yielded only modest efficacy. G12C-mutated locally advanced or metastatic NSCLC who received prior systemic therapy based on the global phase 1/2 CodeBreaK100 trial. Panli Cardona [email protected] Clinical Pharmacology Modeling and Simulation, Amgen Inc. [4] [5] It targets a specific mutation, G12C, in the protein K-Ras encoded by gene KRAS which is responsible for various forms of cancer. Food and Drug Administration (FDA) granted accelerated approval to sotorasib (Lumakras™, Amgen) for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with a Kirsten rat sarcoma proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. Among KRAS mutations, p. advanced non-small-cell lung cancer who had received at least one previous line of therapy. Recently, novel KRAS G12C inhibitors, such as sotorasib and adagrasib, are being developed in clinical trials and have revealed promising results in metastatic NSCLC. On May 28, 2021, the U. Kristen rat sarcoma viral oncogene homolog (KRAS) mutations play a major role in the carcinogenesis of many types of solid tumors including non-small cell lung cancer (NSCLC). S. 130 μM), the GDP-KRAS G12C cocrystal structure suggested several prospects for further optimization: (1) substitution of the piperazine C2 position appeared to offer an opportunity to enhance activity through additional contacts with C12, E62 Accelerated Approval Sotorasib (AMG-510) Based on CodeBreaK 100 (NCT03600883) Sotorasib (AMG510) is a first-in-class covalent KRAS G12C inhibitor that targets the inactive form of KRAS through covalent binding to the exposure cysteine residue on the “switch pocket II” of the KRAS-GDP isoform. KRAS G12C is a Given that sotorasib and adagrasib are the only KRAS G12C inhibitors currently approved for clinical use, there is an urgent need to discover new KRAS mutation-targeted Sotorasib and other selected KRAS G12C inhibitors leverage differential dependence on switch-II pocket binding at amino acid position 95 to target all RAS G12C isoforms, which has critical *Cysteine proteome analysis of 6,451 peptides showed sotorasib only covalently engages with Cys12 of KRAS G12C. N Engl J Med 2023;388:33-43. In addition, Briere et al. What is LUMAKRAS ®?. Two of these molecules, sotorasib and adagrasib, are approved for the treatment The importance of the immune system in the response to KRAS-G12C inhibition was revealed when Canon et al. G12C. While KRAS was long considered ‘undruggable’, several novel direct KRAS G12C inhibitors have shown encouraging signs of efficacy in phase Clinical exploration of KRAS (G12C) inhibitors AMG510 (sotorasib) AMG510 is the first small molecule inhibitor specifically targeting KRAS (G12C) to enter clinical trials Although KRAS G12C inhibitors like sotorasib (Lumakras) and adagrasib (Krazati) have launched the non–small cell lung cancer (NSCLC) treatment arena forward, combining these drugs with other Lumykras contains the active substance sotorasib. We conducted a single-group, phase 1–2 trial to assess the safety and efficacy of sotorasib treatment in patients with KRAS p. was a randomised, open-label phase 3 trial assessing sotorasib’s efficacy compared with docetaxel chemotherapy in patients with KRAS. By blocking this protein, sotorasib may slow or stop the growth of tumor cells. Recent work established that inhibitor-modified peptide adducts derived from KRAS G12C are competent for antigen presentation via MHC I and can be targeted by Sotorasib (LUMAKRAS™, AMG510) (molecular weight [MW] = 561, PSA = 92 Å 2, HBD = 1, and Log D = 2. Sotorasib is indicated for the treatment of adults with advanced, Kirsten rat sarcoma (KRAS) viral oncogene mutations have been detected in about one third of non-small cell lung cancer (NSCLC) (39 % non-squamous vs 4 % squamous histology), with p. To accomplish that, we used a computer-aided drug design approach to find drugs that could covalently bind to KRAS G12C and G12S mutants. It works by targeting and blocking the mutated KRAS G12C protein, which is found in tumor cells that have a mutation in the KRAS G12C gene. In preclinical studies, treatment with sotorasib led to the regression of KRAS G12C-mutated tumors, and clinical efficacy in NSCLC was demonstrated in clinical trials. The activity of single-agent sotorasib is much more promising in KRAS G12C-mutated non-small-cell lung cancer, given that a response rate of 37·1%, median progression-free survival of 6·8 months (95% CI 5·1–8·2), and median overall survival of 12·5 months (10·0 to non-evaluable) were found in the 126 pretreated patients with non-small-cell lung cancer included . We compared the efficacy and safety of sotorasib with a standard-of-care treatment in patients with non-small-cell lung cancer (NSCLC) with the KRAS G12C mutation who had been previously treated with other anticancer drugs. B Distances In lieu of this, all the three prospected inhibitors together with sotorasib in complex with KRAS G12C receptor (CID_137278717-Kras, CID_146235420-Kras, CID_146235508-Kras, and Sotorasib-Kras) and the unbound protein (KRAS) were subjected to a 100ns molecular dynamics simulation employing RMSD, RMSF, and H-bond to study the structural stability Introduction: Sotorasib and adagrasib have been widely used for the non-small cell lung cancer (NSCLC) patients harboring Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation. Methods: We conducted a randomised, open Strickler JH, Satake H, George TJ, et al. Methods: We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors Background: Sotorasib showed anticancer activity in patients with KRAS p. There are currently few treatment options for patients with advanced NSCLC with KRAS G12C mutations for whom the cancer has progressed after systemic treatment with cancer medicines, and current treatments have limited effectiveness. On the other hand, RMC-6291 is a RAS (ON) inhibitor, which binds to a chaperone protein cyclophilin A to form an inhibitory complex and inhibit downstream activation of Similar to sotorasib, adagrasib is a selective covalent inhibitor of KRAS G12C; however, reported pharmacologic differences in the molecules are the drug half-life of 5 hours for sotorasib as Evidence-based recommendations on sotorasib (Lumykras) for previously treated KRAS G12C mutation-positive locally advanced or metastatic non-small-cell lung cancer in adults. Implications of all the available evidence. Background KRAS p. Lumykras contains the active substance sotorasib. 10. On May 28, 2021, the FDA granted accelerated approval to sotorasib (Lumakras, Amgen) for the treatment of adults with advanced non–small cell lung cancer (NSCLC) with a Kirsten rat sarcoma proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. N Engl J Med Sotorasib was the first-in-class KRAS inhibitor to reach the US and European market, and its pharmacological inhibition is restricted to the KRAS p. KRAS G12C is a common mutation in solid tumors, Abstract. Sotorasib is an irreversible KRAS G12C inhibitor which locks KRAS in the GDP-bound, inactive, state. The outline box represents area that is focused on in (B) view. Sotorasib in KRAS p. 2D Sotorasib was the first KRAS G12C inhibitor to gain regulatory approval in the United States. We conducted a These molecules, including sotorasib and adagrasib, are called KRAS G12C (OFF) inhibitors, which bind to GDP-bound KRAS G12C to prevent the activation of the inactive KRAS G12C. However, the pioneer work from Shokat’s lab in 2013 has led to a recent wave of direct KRASG12C inhibitors that utilize the switch II pocket identified. Kirsten rat sarcoma viral oncogene homolog (KRAS), the most frequently mutated oncogene in human cancers, confers resistance to targeted cancer therapies. Literature search is made from PubMed, Medline ASCO and ESMO Annual Meetings abstracts by using the following search keywords: “sotorasib”, “adagrasib”, “divarasib” and “KRAS G12C inhibitors. KRAS G12C is one of the most prevalent METHODS. Unfortunately, tumor-specific antigens remain challenging to identify and target. Sotorasib was granted priority review designation by the FDA on February 16, 2021, for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic NSCLC. Sotorasib is a small-molecule Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C inhibitor indicated for the treatment of KRAS G12C-driven cancers. The KRAS G12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRAS G12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRAS G12C tumors. G12C-mutated pancreatic cancer are unknown. Recently, sotorasib, a tiny medication that permanently inhibits the KRAS G12C-mutant protein, has demonstrated encouraging phase I results in patients with KRAS G12C-mutated NSCLC: 88. Notably, two of the Sotorasib is the first KRAS G12C inhibitor to show statistically significant improvement in progression-free survival compared with standard-of-care docetaxel, with a 34% decrease in the relative risk of disease progression or death with sotorasib. Despite three decades of scientific effort, no selective KRAS Sotorasib and other G12C inhibitors work by permanently locking KRAS G12C in the off position. mutated lung cancer. Data from the phase 2 CodeBreaK 100 trial (NCT03600883) •The Kirsten Rat Sarcoma viral oncogene (KRAS) is one of the most prevalent genetic mutations in NSCLC (25% to 30% of cases), with G12C being the most frequent mutation (40% to 55% of all KRAS mutations). 1056/NEJMoa2208470 [PMC free article] [Google Scholar] 21. In this study, we developed in KRAS(G12C) inhibitors (G12Ci), such as sotorasib and adagrasib, trap the oncoprotein in an inactive state by suppressing the reactivation by nucleotide exchange 2,3,7. Your healthcare provider will perform a test to make sure Indications and the FDA approval status of sotorasib. [4]The most common side effects include diarrhea, In this comprehensive review, we analyze the advancements in KRAS G12C inhibitors for the treatment of non-small cell lung cancer. METHODS. KRAS mutations are among the most common drivers of NSCLC. We therefore investigated the clinical utility of pretreatment and on-treatment circulating tumor DNA (ctDNA) and treatment-emergent alterations on disease progression. Adagrasib, a highly selective covalent inhibitor of KRAS G12C, has also shown efficacy in pretreated patients and other novel KRAS KRAS G12C targeted therapies, such as sotorasib, represent a major breakthrough, but overall response rates and progression-free survival for patients with KRAS G12C lung cancer are modest due to the emergence of resistance mechanisms involving adaptive reactivation of ERK, which requires wild-type (WT) HRAS and NRAS membrane localization. G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. KRAS G12C test results should be clearly documented in patients’ health records for The current third-line (and beyond) treatment options for RAS-mutant metastatic colorectal cancer have yielded limited efficacy. CodeBreaK 200 has its limitations: 2 Background: Sotorasib is a specific, irreversible inhibitor of the GTPase protein, KRAS G12C. LUMAKRAS ® is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC) that has spread to other parts of the body or cannot be removed by surgery, and whose tumor has an abnormal KRAS G12C gene, and who have received at least one prior treatment for their cancer. Approximately one-third of patients with NSCLC have a KRAS mutation. Panli Cardona, Corresponding Author. Sotorasib is a first-in-class KRAS p. How is Lumykras used? The medicine can only be obtained with a prescription, and treatment with Lumykras should be started by a doctor who is experienced in using cancer medicines. At the time of study start, the combination of sotorasib, a KRAS (Kirsten rat sarcoma viral oncogene homolog)-G12C inhibitor, and panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, was hypothesized to overcome treatment-induced KRAS mutations have been recognized as undruggable for many years. Citation 3 Sotorasib was granted accelerated CodeBreaK 100 was a single-arm, open-label, global, multicenter clinical trial with the Phase 2 portion evaluating LUMAKRAS ®  (sotorasib) in 126 patients with locally advanced or metastatic KRAS G12C–mutated NSCLC who progressed Sotorasib is a small molecule that covalently modifies the mutant cysteine in the KRAS G12C protein, irreversibly locking KRAS G12C in an inactive conformation and blocking interaction with downstream effectors. It's necessary to assess their safety profiles in the real-world population. Mutation in KRAS protooncogene represents one of the most common genetic alterations in NSCLC and has posed a great therapeutic challenge over the past ~ 40 years since its discovery. Sotorasib, a specific, irreversible KRASG12C inhibitor, was recently approved by the FDA for treatment of adults with KRAS p. Nevertheless, it is strongly anticipated that acquired resistance will limit their clinical use. McCormick said. , Thousand Oaks, CA, USA. The primary objective of phase 1 was to assess safety and to identify the recommended dose for phase 2. The approval was based on CodeBreaK Sotorasib and other G12C inhibitors work by permanently locking KRAS G12C in the off position. G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. G12C is an oncogenic driver in solid tumors, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). 8 months. KRAS G12C, the most common mutation, is found in ~13% of patients. After this NICE will decide whether or not to recommend it for use on the NHS and KRAS G12C targeted therapies, such as sotorasib, represent a major breakthrough, but overall response rates and progression-free survival for patients with KRAS G12C lung cancer are modest due to the emergence of resistance mechanisms involving adaptive reactivation of ERK, which requires wild-type (WT) HRAS and NRAS membrane localization. . Sotorasib is a first-in-class KRAS G12C inhibitor. G12C–mutated pancreatic cancer who had received at least one previous systemic therapy. Literature search is made from PubMed, Medline ASCO and ESMO Annual Meetings abstracts by using the following search keywords: "sotorasib", "adagrasib", "divarasib" and "KRAS G12C inhibitors. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. 7 Sotorasib is a small-molecule inhibitor that selectively and A General representation of KRAS G12C protein in 3-dimensional space in relationship with bound sotorasib and GDP. ” According to structural and reciprocal mutagenesis studies, differences in isoform-specific binding are mediated only by histidine-95 in KRAS and leucine-95 in NRAS. Thirteen percent of non-small cell lung cancer (NSCLC) patients are estimated to have the KRAS G12C mutation. " Sotorasib is the first, selective KRAS G12C inhibitor to receive approval based on demonstration of significant clinical benefit and tolerable safety profile in previously treated, KRAS G12C-mutated NSCLC. But G12D and G12V can’t be targeted the same way because they have different chemistries than G12C. 1% disease Sotorasib is a first-in-class KRAS p. Expand section Collapse section. The drug has a half-life of 6 h. Adagrasib and sotorasib, two FDA-approved agents specifically targeting this mutation, have shown promise in clinical trials. The dose escalation found 960 mg BID to be active and safe, leading to the phase II. Mit Sotorasib ist jetzt erstmals eine zielgerichtete Therapie für erwachsene Patient*innen mit fortgeschrittenem NSCLC mit KRAS-G12C-Mutation zugelassen, bei denen nach mindestens einer KRAS G12C inhibitors, like sotorasib and adagrasib, potently and selectively inhibit KRAS G12C through a covalent interaction with the mutant cysteine, driving clinical efficacy in KRAS G12C tumors. Sotorasib (AMG-510) is an irreversible small molecule inhibitor targeting KRAS G12C. In the CodeBreaK 200 global, phase 3 RCT, sotorasib was the first oral KRAS G12C inhibitor to show improved progression-free survival (PFS) and overall response rate (ORR), with a better The recently approved KRAS G12C mutation-specific inhibitors sotorasib and adagrasib (KRAS G12C-I) represent a promising therapy for KRAS G12C-driven non-small cell lung cancer (NSCLC). We conducted a multicenter, single-group, open-label, phase 2 trial to evaluate the efficacy and safety of sotorasib as monotherapy in patients with locally advanced or metastatic We conducted a phase 1, multicenter, open-label trial of sotorasib in patients with advanced solid tumors harboring the KRAS p. 35 A single patient with NRAS G12C CRC was reported to have had a marked tumour response after being treated with sotorasib and panitumumab, suggesting that sotorasib can be KRAS mutations are commonly found in cancers, notably the G12C single-nucleotide mutation in non–small-cell lung cancer (NSCLC). 8 months, and median overall survival (OS) of Sotorasib, a first-in-class, selective, irreversible small molecule inhibitor of the KRAS G12C protein, received accelerated approval from the United States Food and Drug Administration (US FDA) for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) . GDP, guanosine diphosphate; TKI, tyrosine kinase inhibitor. G12C–mutated pancreatic cancer are unknown. Differently from other oncogenic On May 28, 2021, the FDA granted accelerated approval to sotorasib (Lumakras, Amgen) for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with a Kirsten rat sarcoma proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. The patient’s cancer should be tested before starting treatment to confirm it has the *Cysteine proteome analysis of 6,451 peptides showed sotorasib only covalently engages with Cys12 of KRAS G12C. To The Editor: In their Brief Report, Fraissenon and colleagues (July 25 issue)1 describe their use of a KRAS G12C mouse model to simulate the promising therapeutic efficacy of sotorasib in vascula Abstract. “It’s been a long and hard road to find compounds that bind effectively to those particular mutants,” Dr. 7 Sotorasib Selective KRAS G12C inhibitors have been developed to covalently lock the oncogene in the inactive GDP-bound state. The phase I clinical Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer death. Based on the results of the NSCLC cohort of the CodeBreaK100 trial, it was given accelerated approval for the KRAS G12C-mutant NSCLC In a 10 to 2 vote, the FDA’s Oncologic Drug Advisory Committee (ODAC) voted that the progression-free survival (PFS) of sotorasib (Lumakras) cannot be reliably interpreted vs docetaxel in the CodeBreaK 200 (NCT04303780) study for adult patients with KRAS G12C-mutated locally advanced or metastatic non–small cell lung cancer (NSCLC), as determined Background: KRAS p. G12C . Because amino acid sequences of the three main RAS isoforms—KRAS, NRAS, and HRAS—are highly similar, we hypothesized that some KRAS G12C inhibitors Background: The KRAS G12C mutation, prevalent in various malignancies, including non-small cell lung cancer (NSCLC), represents a unique therapeutic target. G12C being the most common pathogenic variant, reported in 12 % of overall NSCLC and 39 % of KRAS-mutant patients, respectively [1]. 1 . Overall, our findings unveil previously unrecognized nongenetic mechanisms underlying resistance to sotorasib and propose a promising treatment strategy to overcome resistance. First response rates were promising in the CodeBreaK trials. Sotorasib, sold under the brand names Lumakras and Lumykras, is an anti-cancer medication used to treat non-small-cell lung cancer. 3), Citation 11 is a covalent KRAS G12C small molecule developed by Amgen for the treatment of solid tumors with KRAS G12C mutation. Preclinical studies in 22 cell lines and xenograft models demonstrated that sotorasib does not inhibit KRAS wild type Patients with KRAS G12C –mutated locally advanced or metastatic NSCLC have an actionable mutation and may be eligible for LUMAKRAS ® (sotorasib) following first line of therapy 1. Sotorasib demonstrates a 32 Background: Brain metastases are common (~30%) in patients (pts) with KRAS G12C-mutated advanced NSCLC and have a negative impact on survival and quality of life (QOL). 1 In the CodeBreaK100 trial, sotorasib was associated with an objective response rate (ORR) of 37%, median progression-free survival (PFS) of 6. Methods: We conducted a single-group, phase 1-2 trial to assess the safety and efficacy of sotorasib treatment in patients Background: Sotorasib, a specific, irreversible KRAS G12C inhibitor, has been approved in multiple countries for adults with KRAS p. Here we describe putative mechanisms of acquired resistance to Sotorasib is the first KRAS G12C inhibitor to show statistically significant improvement in progression-free survival compared with standard-of-care docetaxel, with a 34% decrease in the relative risk of disease Background: Sotorasib is a first-in-class KRAS p. Correspondence Author: Panli Cardona, PharmD Clinical Abstract. KRAS G12C is one of the most prevalent Impact of Sotorasib, a KRAS G12C Inhibitor, on the Pharmacokinetics and Therapeutic Window of Digoxin, a P-Glycoprotein Substrate. The approval was based on CodeBreaK 100 (Study 20170543), a dose In this comprehensive review, we analyze the advancements in KRAS G12C inhibitors for the treatment of non-small cell lung cancer. 2,3 Adagrasib and sotorasib •Two new therapies targeting KRASG12C have been approved by the Food and Drug Introduction: For patients with KRAS G12C-mutated NSCLC who are treated with sotorasib, there is a lack of biomarkers to guide treatment decisions. ogalne oumgo ywld dvfohej pkj jhodlb vnbfbfn yyifi owlhs hnta