FDA approves sotorasib with panitumumab for KRAS G12C …
On January 16, 2025, the Food and Drug Administration approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for adult patients with KRAS G12C-mutated metastatic...
KRAS mutation: from undruggable to druggable in cancer
Nov 15, 2021 · Recently, there has been light on the horizon for one specific mutation, KRAS (G12C). With the discovery of a new allosteric site of KRAS (G12C), several irreversible covalently binding...
The KRAS-G12C inhibitor: activity and resistance
Sep 1, 2021 · Although it has long been deemed “undruggable”, with the development of drugs specifically binding the KRAS-G12C mutant protein, clinical trials that directly inhibit oncogenic RAS have recently...
KRAS G12C inhibitor combination therapies: current evidence and ...
Multiple combinations of KRAS G12C inhibitors with other targeted therapies, such as RTK, SHP2, and MEK inhibitors, have been investigated in clinical trials to overcome the resistance. They have demonstrated promising efficacy especially by combining KRAS G12C and EGFR inhibitors for KRAS G12C-mutated colorectal cancer.
Treatment for KRAS G12C-mutated metastatic CRC approved by …
Jan 17, 2025 · The KRAS G12C mutation is present in approximately 3-5% of colorectal cancers, emphasizing the important role of comprehensive biomarker testing in mCRC. By detecting an actionable mutation, eligible patients are now able to receive a corresponding targeted therapy that may lead to improved responses.
KRAS G12C mutation: from undruggable target to potentially …
With the expansion of these inhibitors to other solid malignancies and the reported promising outcomes (20,21), KRAS G12C mutation has the potential to become the next agnostic cancer biomarker in the era of precision oncology.
The prevalence and prognostic significance of KRAS G12C …
2 days ago · The mOS in KRAS G12C mutation, RAS non-G12C mutations, BRAF V600E mutation, and RAS/BRAF V600E WT was 65 months (m), 55m, 19m and 105m respectively. Compared to RAS non-G12C, the mOS of CRC patients with KRAS G12C was (65m vs …
Targeting KRAS G12C in Non-Small-Cell Lung Cancer: Current
Despite efforts to develop drugs aimed at inhibiting KRAS or its signaling pathways, KRAS had remained undruggable for decades. The discovery of a small pocket in the binding switch II region of KRAS G12C has revolutionized the treatment of KRAS G12C-mutated NSCLC patients.
KRAS G12C Inhibitors: New Drugs, A New Hope - Journal of …
The ongoing research into new KRAS G12C inhibitors and their mechanisms offers hope for overcoming these barriers and achieving more durable responses.
KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and …
Oct 1, 2023 · KRAS G12C is the most common KRAS variant at ∼13% of NSCLC cases overall. Approved RAS GTPase inhibitors transform KRASG12C into a predictive biomarker. Real-world studies show significant geographic variation in KRAS G12C prevalence.
Sotorasib is First KRAS Inhibitor Approved by FDA - NCI
Jun 25, 2021 · The discovery and approval of sotorasib “opens up opportunities for developing compounds that bind to other mutant [KRAS] proteins,” Dr. McCormick said. G12C is one of several KRAS mutations found in cancer cells. The two most common KRAS mutations are called G12D and G12V.
Lumakras Plus Vectibix Approved for KRAS G12C-Mutated …
Jan 21, 2025 · The recommended dose of Lumakras for KRAS G12C-mutated mCRC is 960mg orally once daily in combination with panitumumab until disease progression or unacceptable toxicity. The first dose of ...
Sotorasib for Lung Cancers with KRAS p.G12C Mutation
Jun 4, 2021 · Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors in a phase 1 study, and particularly promising anticancer activity was observed in a subgroup of...
The path to the clinic: a comprehensive review on direct KRAS G12C ...
Analyzing amino acid-specific KRAS mutations in the three cancer types responsible for most KRAS mutations, the most common KRAS mutation in NSCLC adenocarcinoma subtype is KRAS G12C (glycine to cysteine) (33.4%), while the most common KRAS mutation in colon and rectal adenocarcinoma and pancreatic ductal adenocarcinoma is KRAS G12D (glycine to ...
Targeting KRAS(G12C): From Inhibitory Mechanism to Modulation of ...
Nov 12, 2020 · Recent advances in medicinal chemistry have established inhibitors targeting KRAS (G12C), a mutation found in ∼13% of lung adenocarcinomas and, at a lower frequency, in other cancers.
An updated overview of K-RAS G12C inhibitors in advanced stage …
Oct 3, 2024 · These mutations are associated with aggressive tumor behavior and resistance to conventional therapies, highlighting the urgent need for targeted interventions. In this comprehensive review, we analyze the advancements in KRAS G12C inhibitors for the treatment of non-small cell lung cancer.
Targeting KRAS in cancer - Nature Medicine
Apr 18, 2024 · The first successes occurred with allele-specific targeting of KRAS p.Gly12Cys (G12C) in non-small cell lung cancer, resulting in regulatory approval of two agents—sotorasib and adagrasib.
KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors
Sep 20, 2020 · We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation. Patients received sotorasib orally once daily. The primary end point was...
Adagrasib/Cetuximab Maintains Efficacy in KRAS G12C–Mutated …
2 days ago · The open-label, nonrandomized, multiple-expansion cohort phase 1/2 trial evaluated the safety and efficacy of adagrasib/cetuximab in patients with unresectable or metastatic KRAS G12C–mutated ...
Targeted therapy meets immunotherapy: a clinical trial for persons …
2 days ago · The primary goal of this trial is to answer this question: Does adding immunotherapy (cemiplimab (Libtayo®), an anti-PD-1 therapy) to standard of care (adagrasib (Krazati®), a KRAS G12C inhibitor, and cetuximab (Erbitux®), an anti-EGFR therapy) for patients with KRAS G12C mutated metastatic CRC (mCRC) significantly improve response rate?The secondary …
FDA Approves Sotorasib with Panitumumab For KRAS G12C …
The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur: On January 16, 2025, the Food and Drug Administration approved sotorasib (Lumakras, Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for adult patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, …
Landscape of KRASG12C, Associated Genomic Alterations, and ...
KRAS G12C was most prevalent in patients with non–small-cell lung cancer, appendiceal, colorectal, tumor of unknown origin, small bowel, and pancreatic cancers. KRAS G12C tumors were genomically distinct from KRAS non-G12C tumors, including variations in STK11, KEAP1, and other gene frequencies.
Acquired Resistance to KRAS G12C Inhibition in Cancer - The New …
Jun 23, 2021 · 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)....
What is KRAS G12C? | LUMAKRAS® (sotorasib)
Learn why understanding the KRAS G12C mutation is an important part of your non-small cell lung cancer (NSCLC) treatment plan. See full Prescribing & Safety Info.
Hepatobiliary Adverse Events Associated With the KRAS p.G12C …
Jan 22, 2025 · The p.G12C mutation in KRAS is commonly found in many cancers and was previously untreatable until drugs like sotorasib were developed. However, up to 15% of patients treated with sotorasib have experienced hepatobiliary adverse events. To investigate whether these side effects are more common among sotorasib users, a pharmacovigilance study is ...
FDA Greenlights Amgen's New Cancer Drug Combo, Boosting …
Jan 17, 2025 · The decision, announced Thursday, applies to adults whose tumors carry the KRAS G12C mutation. Amgen's treatment pairs Lumakras (sotorasib) with Vectibix (panitumumab), an epidermal growth factor ...
FDA Approves Breakthrough for KRAS-Mutated Colorectal Cancer
Jan 19, 2025 · THE U.S. Food and Drug Administration (FDA) approved a novel combination therapy for adults with KRAS G12C-mutated metastatic colorectal cancer (mCRC). This approval, based on results from the CodeBreaK 300 clinical trial, offers a new treatment option for patients who have progressed after prior chemotherapy regimens involving fluoropyrimidine ...
FDA Approves Lumakras With Vectibix for KRAS G12C–Mutated …
6 days ago · Originally published by our sister publication Clinical Oncology News. By Clinical Oncology News Staff. The FDA has approved sotorasib (Lumakras, Amgen) with panitumumab (Vectibix, Amgen) for adult patients with KRAS G12C–mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, who have received prior fluoropyrimidine-, …