KRAS G12C is a predictive biomarker for use of afatinib, dacomitinib, erlotinib, gefitinib, osimertinib, cetuximab, and panitumumab in patients. Non-small cell lung carcinoma and colorectal carcinoma have the most therapies targeted against KRAS G12C or its related pathways [ 5 ].
Non-Small Cell Lung Carcinoma. Colorectal Carcinoma. KRAS G12C serves as an inclusion eligibility criterion in 33 clinical trials, of which 24 are open and 9 are closed. Trials with KRAS G12C in the inclusion eligibility criteria most commonly target colorectal carcinoma, non-small cell lung carcinoma, malignant solid tumor, colorectal adenocarcinoma, and acute myeloid leukemia [ 5 ].
Cetuximab, panitumumab, binimetinib, docetaxel, and fluorouracil are the most frequent therapies in trials with KRAS G12C as an inclusion criteria [ 5 ]. KRAS is altered in KRAS G12C is an inclusion criterion in 14 clinical trials for non-small cell lung carcinoma, of which 10 are open and 4 are closed.
KRAS G12C is an inclusion criterion in 11 clinical trials for malignant solid tumor, of which 10 are open and 1 is closed.
KRAS G12C is an inclusion criterion in 9 clinical trials for colorectal carcinoma, of which 8 are open and 1 is closed. KRAS is altered in 4. KRAS G12C is an inclusion criterion in 3 clinical trials for squamous cell lung carcinoma, of which 1 is open and 2 are closed. KRAS is altered in 3.
KRAS G12C is an inclusion criterion in 3 clinical trials for acute myeloid leukemia, of which 0 are open and 3 are closed. KRAS G12C is an inclusion criterion in 2 clinical trials for pancreatic ductal adenocarcinoma, of which 2 are open and 0 are closed.
KRAS G12C is an inclusion criterion in 1 clinical trial for lung adenocarcinoma, of which 1 is open and 0 are closed. KRAS G12C is an inclusion criterion in 1 clinical trial for malignant colorectal neoplasm, of which 1 is open and 0 are closed.
Of the trial that contains KRAS G12C and malignant colorectal neoplasm as inclusion criteria, 1 is phase 1 1 open [ 5 ]. KRAS G12C is an inclusion criterion in 1 clinical trial for rectal carcinoma, of which 1 is open and 0 are closed.
KRAS G12C is an inclusion criterion in 1 clinical trial for pancreatic carcinoma, of which 1 is open and 0 are closed. KRAS G12C is an inclusion criterion in 1 clinical trial for pancreatic adenocarcinoma, of which 1 is open and 0 are closed. KRAS G12C is an inclusion criterion in 1 clinical trial for esophageal squamous cell carcinoma, of which 1 is open and 0 are closed.A range of clinical trials evaluating sotorasib as monotherapy or in combination with other anticancer agents are currently underway.
KRAS mutations often are associated with therapeutic resistance and poor outcomes. The KRAS p. In preclinical studies, sotorasib produced durable complete tumor regression, providing the basis for a phase I trial to evaluate the drug's safety, pharmacokinetics, and efficacy in patients with advanced solid tumors harboring the KRAS p.
Investigators in the multicenter trial recruited adults with histologically confirmed, locally advanced or metastatic cancers associated with the KRAS p. Patients with untreated brain metastases or recent systemic or radiation therapy were excluded.
Patients received oral sotorasib daily until disease progression or development of unacceptable toxicity. The primary endpoint was safety, and secondary endpoints included various pharmacokinetic parameters, objective response, duration of response, disease control, progression-free survival PFSand duration of stable disease.
No dose-limiting toxicities were reported during the trial. TRAEs occurred in 39 One patient discontinued treatment because of an AE. An additional 33 patients had stable disease for at least 6 weeks. Median duration of response was Among the 34 patients who received the recommended phase II dose, 12 Hong reported that 42 of the 59 patients had some degree of tumor shrinkage.
The subgroup had a median PFS of 6. Three patients had confirmed partial responses persisting for 4. An additional 28 patients had stable disease, resulting in a DCR of The subgroup had a median PFS of 4. Of the 28 patients with other types of tumors, four partial responses were confirmed pancreatic, endometrial, and appendiceal cancers and melanoma and 17 patients had stable disease.
Response duration ranged from 4. The findings from the phase I study are "very encouraging, showing the first step in 'drugging the undruggable,' wrote Patricia M. Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in September 8, The KRASG12C mutation is found in approximately 14 percent of patients with lung adenocarcinoma and 11 percent of patients with non-small cell lung cancer but there are no therapies approved that target this mutation.
KRAS is a guanine-nucleotide-binding protein that acts as a molecular switch inside cells and links to receptor tyrosine kinase activation to intracellular signaling. Louis and colleagues enrolled 76 patients with locally advanced or metastatic malignancies who had received previous standard therapy.
The research group's primary endpoint was toxicity and secondary research endpoints were objective response rate, duration of response, disease control rate, progression free survival and duration of stable disease.
Patients were enrolled in four dose cohorts: mg, mg, mg and mg, taken orally once a day for 21 days and followed up with radiographs and examinations. Initial data from the Phase one study were presented at the 55th Annual Meeting of the American Society of Clinical Oncology earlier this year. The additional follow-up in a larger group of patients being presented at WCLC includes a subset of 34 NSCLC patients enrolled, with 23 of the patients being evaluable for efficacy.
Thirteen of the evaluable patients received the target dose of mg once daily, with seven 54 percent achieving a partial response at one or more timepoints and six 46 percent achieving stable disease, for a disease control rate of percent.
There were no dose-limiting toxicities and no adverse events leading to discontinuation in the 34 NSCLC patients enrolled. Twenty-seven of these patients remain on treatment. Of the 34 patients, only nine Three patients reported grade three treatment-related adverse effects anemia and diarrhea.
There were no grade four or higher TRAEs. I am pleased that we have a promising new oral therapy for this group of patients," Govindan said. Your feedback will go directly to Science X editors.
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Colorectal cancer KRAS — Labs
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Planning for Advanced Cancer. Advanced Cancer and Caregivers. Questions to Ask about Advanced Cancer. Finding Health Care Services. Advance Directives.The principle components of the kit are explained below. Each mutation-specific reaction mix uses a mutation-specific ARMS primer to selectively amplify and enrich the mutated DNA, and then uses a Scorpions primer to detect the mutation during a second amplification reaction see ARMS Scorpions technology.
When the primer is fully matched, the amplification proceeds with full efficiency. When the 3' base is mismatched, only low-level background amplification occurs. Therefore, a mutated sequence is selectively amplified even in samples where the majority of the DNA does not carry the mutation.
Detection of amplification is performed using Scorpions. Scorpions are bi-functional molecules containing a PCR primer covalently linked to a probe. The probes incorporate the fluorophore carboxyfluorescein FAM and a quencher. The latter quenches the fluorescence of the fluorophore. When the probe binds to the ARMS amplicon during PCR, the fluorophore and quencher become separated, leading to a detectable increase in fluorescence.TRACO 2018 - K-RAS and Chaperone proteins
Mutations in the KRAS oncogene are frequently found in human cancers 2—4. The presence of these mutations correlates with a lack of response to certain EGFR inhibitor cancer therapies in patients with metastatic colorectal cancer 6—7, 11— The therascreen KRAS test belongs to an easy and complete workflow with automated reporting.
Public and private payers endorse the value of KRAS testing with strong coverage policies for approved indications. Below is a sample of payers that have published positive coverage policies for KRAS testing. The following payers require that a KRAS test be performed prior to prescribing. Representatives are available from a.
Eastern Time, Monday through Friday. Important: Coverage information provided by QIAGEN is gathered from third-party sources and is presented for informational purposes only. Coverage for KRAS testing varies by patient and is subject to contracting, deductibles, and payment caps.Menu Contact Dictionary Search. What Is Cancer?
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Drug Active in 'Undruggable' KRAS-Mutant NSCLC
Reports, Research, and Literature. Late Effects of Childhood Cancer Treatment. Pediatric Supportive Care. Unusual Cancers of Childhood Treatment. Childhood Cancer Genomics. Study Findings. Metastatic Cancer Research.Mirati Therapeutics, Inc. MRTX is a clinical-stage oncology company developing product candidates to address the genetic, epigenetic and immunological promoters of cancer. The company's precision oncology clinical programs utilize next-generation genomic testing to identify and select cancer patients who are most likely to benefit from targeted drug treatment.
In immuno-oncology, Mirati Therapeutics is advancing clinical programs where the ability of its product candidates to improve the immune environment of tumor cells may enhance and expand the efficacy of existing cancer immunotherapy medicines when given in combination.
The company's preclinical programs include potentially first-in-class and best-in-class product candidates specifically designed to address mutations and tumors where few treatment options exist. The company approach each of its discovery and development programs with a singular focus: to translate its deep understanding of the molecular drivers of cancer into better therapies and better outcomes for patients.
The company's clinical pipeline consists of two clinical-stage product candidates: sitravatinib and mocetinostat. The company also have a KRAS inhibitor program in preclinical development. The company's clinical and preclinical programs are summarized in the chart below:. Blocking the signaling of these RTKs enhances the ability of T-cells a type of white blood cell that is of key importance to the immune system to recognize and eliminate tumor cells and modifies the tumor immune environment to enable a more productive immune response.
The ability of sitravatinib to enhance the activity of immune checkpoint inhibitors was demonstrated in nonclinical cancer models. This clinical trial is designed to assess the potential of sitravatinib to inhibit several important immunosuppressive pathways that may be important in overcoming resistance to checkpoint inhibitor therapy.
As previously reported at the IASLC 18th World Conference on Lung Cancer, as of August 10,three of 11 evaluable patients who had relapsed after previous checkpoint inhibitor treatment experienced a confirmed partial response and seven of the 11 evaluable patients were continuing to receive treatment in the clinical trial, with treatment duration ranging from four months to Early safety data indicated an acceptable profile and manageable adverse events.
Based on the data presented, the pre-defined criteria for expansion were met and the next stage will enroll a cumulative total of 34 patients. The company expect to report further data on checkpoint inhibitor refractory patients from this clinical trial in mid Dysregulation of RTKs through genetic alteration or uncontrolled expression is associated with multiple processes relating to human cancer, including tumor growth and metastatic progression, as well as tumor angiogenesis.
Sitravatinib potently inhibits a subset of these RTKs, including the TAM and split family receptors and RET, which are key regulators of signaling pathways that direct cell growth and survival.
Through the genetic selection of patients with tumors that are driven by one or more of these dysregulated RTKs, there are multiple opportunities to develop sitravatinib as a targeted agent.
These mutations are estimated to be present in a total of 5. The company reported early data from this clinical trial in January showing that as of December 9,of the four evaluable patients with RET genetic alterations at the time, there was one patient with stable disease, one unconfirmed partial response and one confirmed partial response. The confirmed partial response is the first example of clinical activity for sitravatinib in a patient with a CBL mutation.
Inactivating mutations in CBL occur in approximately 1. To date, sitravatinib safety data indicate an acceptable profile and manageable adverse events. The company expect to provide an update on this clinical trial in mid