Kras g12d clinical trials. Apr 4, 2023 · Abstract.

Kras g12d clinical trials Now Roche is getting in on the act with GDC-7035 in a phase 1 study in KRAS G12D-mutated solid tumours. Clinical features including age, sex and disease stage were not associated with the KRAS grouping in PC and CRC. KRAS is the most frequently mutated oncogene in cancer. Clinical Trials for KRAS G12D. Clinical trials look at new KRAS G12D mutation is one of the most prevalent subtypes in RAS mutant cancers. The study is expected to last approximately 5 years. Open to people ages 18 years and up. KRAS G12D (G12D) is one of the most frequent oncogenic driver mutations, and is especially common in pancreatic (PDAC) and colorectal (CRC) cancers. INCB161734 demonstrates strong antitumor activity when orally administered to immunocompromised mice Jan 19, 2022 · Previously published pre-clinical data demonstrate effective delivery of exosomes loaded with siRNA targeting KRAS G12D leading to tumor control in various murine models of PDAC. Clinical trials are also called clinical research studies. ELI-002 2P is a vaccine comprised of lymph-node targeted Amphiphile (Amph)-modified G12D and G12R mutant KRAS peptides with an Amph-modified CpG oligonucleotide adjuvant designed to expand polyfunctional mutant KRAS-specific T cells. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated by Jul 8, 2024 · KRAS G12D is the most frequently mutated oncogenic KRAS subtype in solid tumors and remains undruggable in clinical settings. Jun 27, 2024 · The first patient has been dosed in the monotherapy portion of a Phase 1 clinical trial evaluating QTX3046, a KRAS G12D-selective inhibitor, and patient dosing has begun in the combination portion Jan 4, 2024 · About QTX3034 and the Phase 1 Clinical Trial. Jun 1, 2022 · Prospective clinical trials are warranted to determine the therapeutic potential of this therapy in pancreatic cancer and other cancers that express KRAS G12D. As potentially viable regimens are identified, Phase 1b expansion cohorts may be. Here, we report preliminary results of the dose escalation part of a first-in-human phase 1 A Phase 1/2 Multiple Expansion Cohort Trial of MRTX1133 in Patients with Advanced Solid Tumors Harboring a KRAS G12D Mutation NOT ENROLLING 877-DF-TRIAL (877-338-7425) Inclusion Criteria. 6 Among the various KRAS mutations, G12D is the most prevalent, occurring in 37. In Phase 2, Dec 9, 2024 · Finally, nanoparticle-formulated mRNA cancer vaccine, V941, is under development, targeting prevalent KRAS mutations (G12A, G12D, G12V, G13D, and G12C). report the potent preclinical and clinical anti-tumor efficacy of a KRAS G12D-specific inhibitor, HRS-4642, and its sensitizing combinational strategy with carfilzomib. The so-called G12D mutation in the KRAS gene is common in people with some solid tumors. bioavailable KRAS G12D inhibitor, strongly efficacious against . View Clinical Trials for KRAS G12R KRAS G12R serves as an inclusion eligibility criterion in 4 clinical trials, of which 3 are open and 1 is closed. The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. 2 and 32. We investigated the effects of inhibiting the KRAS G12D mutant protein with MRTX1133, a non-covalent small molecule inhibitor of KRAS G12D, on early and advanced PDAC and its influence on the tumor microenvironment. These trials are in early dose-escalation stages, and no clinical combinations have been proposed yet. 5% of all KRAS mutations, respectively. The clinical trials on this list are studying kras g12d inhibitor rmc-9805. KRAS G12D was also most common among many other tumor types including PDAC Jan 22, 2024 · Background: KRAS mutations occur in 25% of human tumors, frequently in pancreatic where over 85% relapse after locoregional treatment. Apr 18, 2024 · The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. Additionally, other mutant-specific inhibitors (e. Activating mutations in codon 12, especially G12D, have the highest prevalence across a range of carcinomas and adenocarcinomas. Nov 28, 2022 · Further studies and clinical trials are needed to investigate this therapy on a larger scale, and to identify other KRAS-G12D-reactive TCRs which could be utilized for similar therapies (58, 59). Jun 24, 2024 · Cell Research - Combination therapy of KRAS G12V mRNA vaccine and pembrolizumab: clinical benefit in patients with advanced solid tumors loaded with KRAS G12V but not with KRAS WT or G12D Dec 27, 2024 · Numerous combinatorial therapies involving KRAS inhibitors are in clinical trials aiming to overcome therapy resistance. Most recently, pan-KRAS inhibitor RMC The main purpose of this study is to assess safety & tolerability and antitumor activity of LY3962673 as monotherapy and in combination with other chemotherapy agents in participants with KRAS G12D-mutant advanced solid tumor types. ELI-002-2P covers the KRAS G12D and G12R variants. Colorectal Carcinoma | Solid Tumor, Adult | KRAS G12D United States Immuneering Corporation The KRAS G12D mutation refers to the presence of an aspartic acid residue (glycine at position 12 is mutated to aspartic acid). et al. May 10, 2023 · Recent studies reveal that nearly one in seven human cancers exhibit KRAS alterations, contributing to an estimated 19. More information on the trials can be obtained by calling PanCAN. One trial is aimed at decreasing the activation of KRAS using son of Multiple Approaches to Targeting KRASG12D Mutant Cancers - a Large Unmet Medical Need Revolution Medicines Clinical Approaches to G12D KRASG12D Frequency by Tumor Type RMC -6236 RAS(ON) Multi-Selective* RMC 9805 RAS(ON) G12D-Selective • Noncovalent, selective inhibitor of mutant and wild-type RAS(ON) proteins • Targeted agent for SOC Feb 16, 2024 · MRTX1133 has demonstrated potent in vitro and in vivo antitumor efficacy against KRAS G12D-mutant cancer cells, especially in PDAC, leading to its recent initiation of a phase I/II clinical trial. KRAS is one of the most frequently mutated oncogenes in various cancers. Astra’s other work in KRAS includes AZD4625 and AZD4747 (both G12C), but these are at the preclinical stage, and Astra is some way behind the KRAS leaders. Targeting KRAS mutations beyond G12D Sep 6, 2023 · MRTX1133 is a highly selective inhibitor of KRAS G12D mutation, being studied in a phase I/II clinical trial (NCT05737706) for safety, tolerability, and anti-tumor activity in patients with advanced solid tumor malignancy with this mutation. All ages Under 18 Over 18. Clinical trials look at new However, in a small phase II clinical trial of 16 NSCLC patients with KRAS G12D mutation, bortezomib showed only a modest disease control rate of 40%, only 1 objective response (ORR 6%), and a PFS of 1 month . ASP3082 is a potential new treatment for solid The purpose of this study is to find out if ASP3082 is effective and safe as a treatment in advanced cancers with KRAS G12D mutation. Jul 11, 2023 · The G12D variant is also a major target for drug discovery efforts, such as Mirati’s lead compound MRTX1133, which is in clinical trials for patients with advanced solid tumors harboring a KRAS G12D mutation. Apr 1, 2024 · Although multiple different KRAS mutant isoforms occur in PDAC, the G12D mutation is the most common, occurring in ∼40% of cases . The recent approval of sotorasib (AMG510), a small-molecule … Sep 5, 2022 · The study is being conducted to evaluate the safety and tolerability of HRS-4642 in patients with advanced solid tumors harboring KRAS G12D mutation. The Jan 24, 2023 · In preclinical studies, ASP3082 selectively degraded the KRAS G12D-mutated protein and showed growth inhibitory activity in KRAS G12D-mutated cancer cells but not in KRAS-wildtype cancer cells. As mentioned, the G12R mutation also occurs at high frequency in PDAC (17% of all KRAS mutations). At MD Anderson, we have a number of clinical trials targeting KRAS. 272. Jan 22, 2024 · We compared the survival outcomes between patients with KRAS G12D mutation (G12D group) and those with non- KRAS G12D mutations (non-G12D group) in terms of progression-free survival (PFS) and overall survival (OS), using the Kaplan–Meier method and the log-rank test. However, the KRAS grouping was May 13, 2024 · As a therapeutic class, TCRs have been developed targeting KRAS G12V 16,17 and KRAS G12D. The analysis of cell lines overexpressing classic KRAS substitutions Jan 9, 2024 · ICH GCP; US Clinical Trials Registry; Clinical Trial NCT06218914; A Study of NT-112 in HLA-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/ or Metastatic Solid Tumors Positive for the KRAS G12D Mutation Jan 3, 2024 · Still, the first clinical data with a G12D inhibitor, Jiangsu Hengrui’s HRS-4642, disappointed at last year’s ESMO meeting, so the remaining players here still have questions to answer. This study will consist of a phase 1 dose escalation part and phase 2 dose expansion part. The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. 3 million new cancer cases worldwide in 2020. Additional RAS(ON) Inhibitors in the company’s pipeline include RMC-0708 (KRAS Q61H) which is currently in IND-enabling development, RMC-8839 (KRAS G13C), and additional compounds targeting other RAS Dec 9, 2022 · Clinical trials of mutant-specific KRAS G12C inhibitors have shown promising activity 7,8,9,10,11,12. ASP3082 is a potential new treatment for solid tumors in people who have the G12D mutation in their KRAS gene. They review the progress of these combinations, discuss the challenges, and propose future research directions. Here, we report preliminary results of the dose escalation part of a first-in-human phase 1 study of HRS-4642 in patients (pts) with advanced KRAS G12D mutant solid tumors. Clinical trials, shows promise as monotherapy or in combination with pembrolizumab for NSCLC, CRC and PDAC patients (NCT03948763) [7]. 0% of pancreatic cancer cases, 12. regimen. Patients were divided into three groups according to the KRAS mutation status: the G12D (mutated in KRAS G12D), non-G12D (mutated in KRAS, but not G12D), and wild-type (WT; no KRAS mutation) groups. Regulations. 5% of colorectal cancer cases, and 4. Study drug QTX3034 for patients with KRAS G12D solid tumors (QTX3034-001) What is the Purpose of this Study? We are doing this study to see if the study drug, QTX3034, either with or without cetuximab, is safe and effective for treating KRAS G12D mutated cancer. It's worth noting that the cyclic peptide molecule in this study has very potent inhibitory activity against cells with a KRAS G12D mutation. 4 and 4. Mar 11, 2024 · Currently, five KRAS-G12D inhibitors are undergoing clinical trials, including the non-covalent inhibitor MRTX1133, the active-state inhibitor RMC-9805, and the KRAS-G12D degrader ASP3082. We have Jan 19, 2022 · The RAS oncogene is both the most frequently mutated oncogene in human cancer and the first confirmed human oncogene to be discovered in 1982. With inhibitors to KRAS-G12D now entering clinical trials, understanding the biology of KRAS-G12D cancers, and identifying biomarkers that predict therapeutic response is crucial. The potential benefit of INCB161734 for patients with . The vaccine contains synthesized peptides (short chains of amino acids) that can launch immune cells to target cancer cells with these mutations. After decades of research, in 2013, the Shokat lab achieved a seminal breakthrough by showing that the activated KRAS isozyme caused by the G12C mutation in the KRAS gene can be directly inhibited via a newly unearthed switch II pocket. Patients with G12D-mutated disease experience poor treatment outcomes, representing a significant unmet medical need. Showing trials for . To learn more about what to expect when taking part in a clinical trial, visit our Clinical Trial Information page. To estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups Mar 21, 2022 · KRAS G12D inhibitors are currently have promising efficacy in preclinical studies 6 and are expected to soon enter clinical trials. mutant tumors. Jan 1, 2022 · range of carcinomas and adenocarcinomas. Trial ID CA246-0005 | NCT05737706. Targeting KRAS mutations beyond G12D Dec 8, 2016 · A conversion of the amino acid glycine (G) to aspartic acid (D) at this site, hereafter referred to as KRAS G12D, is the most frequent KRAS mutant in human gastrointestinal cancers and has been May 31, 2023 · The surprising synergy in KRAS G12V samples with combination therapy and the important synergistic change in cytokine patterns suggests potential strong immune stimulatory anti-cancer effects of MRTX1133 & 5FU against mCRC and pancreatic cancer cells regardless of KRAS G12D mutation which should be considered when including patients with We would like to show you a description here but the site won’t allow us. iExosomes may work Genes contain genetic code which tell the body which proteins to make. , now a wholly owned subsidiary of Bristol Myers Squibb, the company that makes the drug. 2. Dec 23, 2024 · NT-112 in HLA-C*08:02-Positive Adult Subjects With Unresectable, Advanced, and/ or Metastatic Solid Tumors Positive for the KRAS G12D Mutation open to all eligible people Phase I Study of NT-112, an autologous T-cell therapy product genetically engineered to express an HLA-C*08:02-restricted T cell receptor (TCR), targeting KRAS G12D mutant Jun 27, 2024 · QTX3046 is a KRAS G12D-selective inhibitor. Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented Kirsten rat sarcoma viral oncogene homolog [KRAS] G12D mutation and has received prior standard therapy and the investigator does not see any further clinical benefit from continuing such targeted therapy, or is ineligible to receive or has refused standard approved Oct 4, 2024 · KRAS G12D clinical trials at UC Irvine . 5a). 4% [36/220]). KRAS Nov 21, 2022 · Mirati’s research team discovered MRTX1133 through a structure-based drug design strategy, which is a non-covalent inhibitor that can bind to the inactive and activated states of KRAS-G12D Jan 25, 2022 · Cell Discovery - KRAS(G12D) can be targeted by potent inhibitors via formation of salt bridge (G12C) inhibitors have shown promising results in recent clinical trials, Canon, J. ASP3082 may work by directing proteins found in your body to block the growth of cancer cells. Jan 12, 2023 · MRTX1133 is the first KRAS-blocking drug to show promising results in mouse models of pancreatic cancer with KRAS G12D mutations. GFH375/VS-7375 is identified as the lead discovery programme from the Verastem Oncology discovery and development partnership with GenFleet Therapeutics. 083 nM. A separate Phase 1 trial May 13, 2024 · vaccines targeting KRAS G12D and G12V. A Jun 25, 2021 · In fact, several KRAS G12D inhibitors are in development and, according to Dr. Nov 12, 2018 · Rapid clinical improvement and substantial disease regression were achieved in one patient with a confirmed response on this trial, similar to that previously observed in two other patients with advanced KRAS G12D-mutant lung adenocarcinomas who received bortezomib on separate clinical trials. Methods: This is a single arm, single institution, phase I trial evaluating treatment with KRAS G12D-siRNA loaded exosomes. Of the trials that contain KRAS G12V as an inclusion criterion, 3 are phase 1 (3 open) and 3 are phase 1/phase 2 (2 open). Dose expansion cohorts will consist of patients with KRAS G12D-mutant pancreatic, colorectal, lung The KRAS G12D mutation is the most prevalent mutation form that drives the most prevalent type of pancreatic cancer 34. “A KRAS inhibitor was considered the holy grail of oncology, but the Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented Kirsten rat sarcoma viral oncogene homolog [KRAS] G12D mutation and has received prior standard therapy and the investigator does not see any further clinical benefit from continuing such targeted therapy, or is ineligible to receive or has refused standard approved therapies (no limit to the Nov 11, 2024 · KRAS G12D clinical trials at UCLA . Both Phase 1 clinical trials are enrolling patients with KRAS G12D mutations in dose escalation cohorts as monotherapy and in combination with cetuximab. NT-112 in HLA-C*08:02 May 29, 2024 · This clinical trial is now enrolling patients with advanced solid tumors harboring a KRAS G12D mutation. Apr 18, 2024 · Sotorasib and adagrasib, the first clinical KRAS G12C inhibitors, entered trials in non-small cell lung cancer (NSCLC), in which the prevalence of the KRAS G12C allele is approximately 12% PHILADELPHIA – A small molecule inhibitor that attacks the difficult to target, cancer-causing gene mutation KRAS, found in nearly 30 percent of all human tumors, successfully shrunk tumors or stopped cancer growth in preclinical models of pancreatic cancer, researchers from Penn Medicine’s Abramson Cancer Center showed, suggesting the drug is a strong candidate for clinical trials. KRAS G12D . About Mirati Therapeutics, Inc. Methods: We conducted a retrospective, records-based analysis of 2,805 patients with PDAC from across 299 community-based oncology clinics. ELI-002 7P is a lymph node targeted immunotherapy comprised of Amphiphile (Amph)-modified G12D, G12R, G12V, G12C, G12A, G12S and G13D mutant KRAS peptides together with an Amph-modified CpG oligonucleotide adjuvant. 24, 2023 — Researchers have uncovered a functional role for KRAS mutations in pancreatic cancer and rapidly translated these findings into a novel therapeutic approach combining a KRAS G12D Dec 9, 2024 · There are two additional immunotherapy (vaccine) trials sponsored by Elicio Pharmaceutical. May 24, 2024 · The ongoing first-in-human, multi-center clinical trial (NCT06385925) In addition to the KRAS G12D program, the company has several molecules in development, including TSN084, Jul 8, 2024 · Zhou et al. In KRAS G12D, meanwhile, disappointment abounds, with ESMO data on Astellas’s degrader ASP3082 adding to underwhelming results with HengRui’s inhibitor HRS-4642 a year earlier. In this Review, we discuss the Further studies and clinical trials are needed to investigate this therapy on a larger scale, and to identify other KRAS-G12D-reactive TCRs which could be utilized for similar therapies (58, 59). evidence of clinical activity are available to recommend Phase 2 regimens. No data are currently available on in vivo efficacy. Based upon transcriptome data and immunostaining results from KRAS-mutant NSCLC, KRAS-G12D point mutation negatively correlated with PD-L1 level and secretion of chemokines CXCL10/CXCL11 that led to a decrease in CD8 + TILs, which in turn yielded an immunosuppressive TIME. G12D mutation results in constitutively active signaling, including hyperactivation of the ERK and PI3K pathways, which KRAS G12D and KRAS G12V are most prevalent, at 39. gov. Nov 6, 2024 · BOSTON, MA – November 6, 2024 – Affini-T Therapeutics, Inc. 03), TH-Z827 conferred anti-proliferative effects with IC 50 values of 4. In this Review, we discuss the genomics and biology of KRAS-G12D adenocarcinomas, May 31, 2023 · Patients were divided into three groups according to the KRAS mutation status: the G12D (mutated in KRAS G12D), non-G12D (mutated in KRAS, but not G12D), and wild-type (WT; no KRAS mutation) groups. Feb 3, 2024 · Furthermore, preclinical development of a KRAS G12D inhibitor (MRTX 1133) has shown promising results and MRTX 1133 is currently in phase 1 clinical trial 21. Here, we developed a high affinity, selective, long-acting, and non-covalent KRAS G12D inhibitor, HRS-4642, with an affinity constant of 0. Oct 4, 2024 · G12D. 2 KRAS G12D mutations also confer a worse prognosis when compared to KRAS-wildtype tumors. Background: KRAS G12D mutation subtype is present in over 40% of pancreatic ductal adenocarcinoma (PDAC), one of the leading global causes of cancer death. The primary objectives are to Sep 19, 2023 · The company’s RAS(ON) Inhibitors RMC-6236 (RAS MULTI), RMC-6291 (KRAS G12C) and RMC-9805 (KRAS G12D) are currently in clinical development. , a clinical stage biopharmaceutical company focused on the development of precision immunotherapies for treatment of patients with solid tumors, today announced that a Trial-In-Progress poster for the Company’s Phase 1 clinical trial evaluating AFNT-211 targeting KRAS G12V will Jan 19, 2023 · The Phase 1/2 clinical trial will launch in early 2023 with plans for multiple expansion cohorts in pancreatic, colorectal, lung and other KRAS G12D tumor types. Cancer vaccine ELI-002 2P enhances lymph node This first-in-human clinical trial will begin with an exploration of MRTX1133 dose and. Jul 15, 2024 · Verastem Oncology has announced the dosing of the first patient with GFH375/VS-7375, a potent and selective oral KRAS G12D (ON/OFF) inhibitor, as part of a Phase I/II clinical trial in China. In the even more crowded KRAS G12C arena, BridgeBio today said the FDA had cleared the IND for BBO-8520; the trial is not yet listed on clinicaltrials. These compounds possess a Oct 23, 2008 · Of the tumors evaluated for K-ras mutations, 42. Here, we provide a summary of the recent advancements related to the use of MRTX1133 for treating KRAS G12D -mutant PDAC, focusing on its efficacy We would like to show you a description here but the site won’t allow us. Moreover, multiple pan-KRAS and pan-RAS inhibitors are in clinical trials with promising efficacy. The QTX3034 Phase 1 clinical trial will initially enroll patients with KRAS G12D mutations in dose Background: KRAS G12D mutation is one of the most prevalent subtypes in RAS mutant cancers. Study of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation Dec 13, 2024 · QTX3544 will become privately held Quanta’s third project to hit the clinic, following its “G12D-preferring” pan-KRAS project QTX3034, and G12D-selective inhibitor QTX3046. ≥18 years old; Locally-advanced or metastatic solid tumor with KRAS G12D mutation; For Part 1 and Part 2 Combination Groups 1 and 2: Disease progression on prior standard treatment, intolerance to or ineligibility for standard treatment, or no available standard treatment to improve the disease outcome We would like to show you a description here but the site won’t allow us. Aug 10, 2023 · Currently, 45 (LUNA18) is undergoing Phase 1 clinical trials in Japan/USA. , a clinical stage biopharmaceutical company focused on the development of precision immunotherapies for treatment of patients with solid tumors, today announced that the first patient has been dosed in the Company’s Phase 1 clinical trial evaluating AFNT-211 targeting KRAS G12V. Researchers involved in NCI’s RAS Initiative, as well as others, have also made progress designing pan-KRAS inhibitors—drugs that work against several different KRAS mutant proteins. g. Oct 30, 2024 · Furthermore, lentiviral expression of either NRAS G12D or KRAS G12D in CD34 + CD45 + cells from four patient-derived AML-iPS cell lines of different genetic groups 30 induced myeloid maturation in Treatment via mesenchymal stem cell-derived exosomes with KRAS G12D siRNA is intended for patients with metastatic pancreatic cancer or PDA with KRAS G12D mutation, but Phase I trial for this treatment is not yet recruiting. implemented to ensure collection of sufficient safety and PK information, and early. The current Patent Highlight presents compounds that directly bind to KRASG12D, selectively inhibiting its activity. Molina-Arcas and Downward review how oncogenic KRAS creates an immune-suppressive tumor microenvironment, providing a rationale for the combination of KRAS inhibitors with immunotherapies. This article aims to describe the clinicopathologic characteristics of KRAS G12D lung cancer and outcomes within this population by co-mutation status. The purpose of this study is to characterize the safety and tolerability of MRTX1133 as monotherapy or combined with cetuximab in patients with advanced KRAS G12D-mutant solid tumors, and to evaluate the pharmacokinetics (PK) of MRTX1133. The combination therapy led to durable tumor elimination A clinical trial helps us learn if a new potential medicine or treatment works and how it works. Apr 9, 2024 · Consistent with this, case studies from the Phase 1/1b RMC-6236 monotherapy clinical trial are featured, describing two patients with advanced KRAS-G12V NSCLC and KRAS-G12D PDAC, respectively, who Apr 11, 2024 · Other KRAS G12D inhibitors with preclinical updates at the conference included Revolution Medicines’ clinical-stage RMC-9805, which works by inhibiting the KRAS protein in its “on” state Aug 30, 2022 · The first trial of a KRAS G12D-directed cell therapy is recruiting patients, with an estimated completion date of 2028. , KRAS G12D), as well as pan-KRAS inhibitors or RAS(ON) multiselective inhibitors, are entering clinical trials and demonstrating promising results. Meanwhile, results from the ongoing clinical trial for HLA-A*11:01+ patients are eagerly awaited. ASP3082 targets the KRAS G12D mutation, blocking its ability to send signals that turn on cancer cells and cause them to grow and spread. The company has claimed that its assets have favourable preclinical properties; now it must show that these make a difference in the clinic. Clinical features Nov 1, 2023 · With inhibitors to KRAS-G12D now entering clinical trials, understanding the biology of KRAS-G12D cancers, and identifying biomarkers that predict therapeutic response is crucial. org at 877. Hence, further data are imperative to broaden the Dec 23, 2024 · This is a Phase 1/2 study to assess the safety and efficacy of ELI-002 7P immunotherapy (a lipid-conjugated immune-stimulatory oligonucleotide [Amph-CpG-7909] plus a mixture of lipid-conjugated peptide-based antigens [Amph-Peptides 7P]) as adjuvant treatment in subjects with solid tumors with mutated KRAS/NRAS. The drug not only inhibits tumor growth but also enhances the immune system's ability to attack the cancer cells. Although these advancements inspire optimism, we stand on the cusp of a thrilling chapter in KRAS-targeted treatments, with many mysteries yet to be unraveled. Notable antitumor effects of ASP3082 have been demonstrated when intravenously administered weekly in mice xenografted with KRAS G12D-mutated cancer cells. 1. Sep 20, 2024 · Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented Kirsten rat sarcoma viral oncogene homolog [KRAS] G12D mutation and has progressed after receiving all available standard approved therapies (no limit to the number of prior treatment regimens). HRS-4642 demonstrated robus … Mar 27, 2024 · For the epitope cassettes, constructs (SLATE 20×1, KRAS 4×1, KRAS 4×1 + TP53-R213L, KRAS 4×1 + TP53-S127Y, KRAS 1×4 G12D, KRAS 1×4 G12V and KRAS 4×4) were cloned into pLxCMT vector; then Apr 4, 2024 · Kopetz has done extensive work on KRAS mutations in colorectal cancer and will be honored with a the AACR-Waun Ki Hong Award for Outstanding Achievement in Translational and Clinical Cancer Research at the 2024 American Association for Cancer Research (AACR) Annual Meeting. This retrospective cohort study aims to investigate whether detection of the KRAS G12D mutation subtype in PDAC patients is a determinant of prognosis across all stages of disease. This study wil Dec 6, 2022 · Aug. May 28, 2024 · BOSTON, MA – May 28, 2024 – Affini-T Therapeutics, Inc. May 31, 2023 · Background: RAS mutations occur in 25% of solid tumors with G12D being the most frequent variant. Building upon . About 93% of PDACs have KRAS mutations, with G12D (∼42% of cases) and G12V (∼32% of cases) being the most common. Apr 4, 2024 · According to the preclinical therapeutic impact of the KRAS-specific G12D inhibitor, 9 we can expect a significant improvement in the prognosis of cancer with KRAS G12D mutation: the objective response to the first-line KRAS G12D inhibitor might increase the resectability in the conversion surgery in the advanced cancer patients, especially in Feb 16, 2024 · KRAS mutations drive oncogenic alterations in numerous cancers, particularly in human pancreatic ductal adenocarcinoma (PDAC). Astra paid Usynova $24m up front last November for what was then a preclinical project. Revolution Medicines have taken a different approach, developing covalent tri-complex inhibitors that target the active form of RAS, with their multi-RAS and KRAS G12C inhibitor already in clinical trials. RMC-9805’s safety profile also looks cleaner than both ASP3082 and Revolution’s own pan-KRAS inhibitor, RMC-6236. Sep 30, 2024 · That last asset is UA022, a KRAS G12D inhibitor now revealed to carry Astra’s code AZD0022. 7. The company also initiated the combination phase of its ongoing Phase 1 trial evaluating QTX3046, a G12D-selective KRAS inhibitor, with cetuximab, an EGFR inhibitor. KRAS G12D is a predictive biomarker for use of afatinib, dacomitinib, erlotinib, gefitinib, osimertinib, cetuximab, and panitumumab in patients. The effectiveness of cetuximab was significantly associated with K-ras mutation status (P=0. 7 μM, respectively (Fig. ELI-002-7P (AMPLIFY) trial,is a pan-KRAS trial covering G12D, G12R and five other KRAS variants. Jan 18, 2024 · About this study. 1 research study open to eligible people . All Female Male . It’s like a puzzle: You can potentially divide all these mutations into individual cancers, which are targeted with different agents. Notes This article was updated on Aug 15, 2023 · KRAS is the most frequently mutated oncogene in cancer. Nov 20, 2024 · KRAS is one of the most frequently mutated oncogenes. Of the trials that contain KRAS G12R as an inclusion criterion, 2 are phase 1 (2 open), 1 is phase 1/phase 2 (1 open), and 1 is phase 2 (0 open). Apr 19, 2024 · GenFleet Receives IND Approval from China's NMPA for GFH375, an Oral KRAS G12D (ON/OFF) Inhibitor, in a Phase I/II Clinical Trial Treating Advanced Solid Tumor Patients with KRAS G12D Mutation Mar 11, 2024 · New drugs targeting the KRAS oncoprotein provide only short-term clinical benefit. The study follows a multicenter, open-label, dose-escalation, and dose-expansion design. “Over 90% of pancreatic cancers have a KRAS G12D mutation, so if you could develop a drug that inhibited KRAS G12D that would have implications not only for lung cancer, but for other cancers as well,” says Dr Burns. KRAS G12D mutations occur in approximately 15% of patients with NSCLC with KRAS mutations (Xie et al. Multiple targeted therapies have been interrogated that inhibit KRAS-mediated downstream effector pathways in clinical trials, although the therapeutic benefits are limited . All three patients were never smokers with advanced Jan 4, 2024 · Quanta’s KRAS inhibitor pipeline includes three programs: QTX3034, a multi-KRAS inhibitor with G12D-preferring activity (G12D+ multi-KRAS), anticipated to enter clinical trials in 1Q24; QTX3046 Jun 21, 2024 · The colorectal cancer clinical trials for adagrasib were funded by Mirati Therapeutics Inc. To date, no marketed mutant-selective and potent KRASG12D inhibitors are available. 6226, M-F, 7:00am-5:00pm PT. This is the first study where ASP3082 is being tested in humans. In this Review, we discuss the genomics and biology of KRAS-G12D adenocarcinomas, including histological features, transcriptional landscape, the immune Feb 1, 2024 · The new vaccine is able to activate immune cells that target different KRAS mutations called KRAS-G12D and KRAS-G12R, which drive about 90% of pancreatic cancers and 40% of colon cancers. Oct 28, 2024 · If this number holds up, RMC-9805 will look better on a cross-trial basis than Astellas’s G12D degrader ASP3082, which recently produced an ORR of 19% in relapsed pancreatic cancer. This work provides novel therapeutics for solid tumor patients harboring KRAS G12D mutation, for whom effective targeted therapies are lacking. 01 Oct 9, 2024 · Revolution’s RMC-9805 is being tested alone and in combination with the pan-KRAS inhibitor RMC-6236 in a phase 1 trial in KRAS G12D-mutant solid tumours. McCormick, will likely enter clinical trials in the next year or so. 7,8 Sep 11, 2023 · As ongoing clinical trials guide the best strategy for KRAS G12C PC, new inhibitors of KRAS G12D are entering the clinic with much excitement for the potential to extend clinical benefit to patients whose PC harbors this most common mutation. The 2022 Cancer Discovery paper was funded by NIH grants R01 CA233736, U54 OD020355, P30 CA008748, and CTSA UL1TR00457. mutant disease is under investigation in an ongoing clinical trial (NCT06179160). , 2021). Sep 24, 2023 · The oral, covalent, mutant-selective KRAS inhibitor, RMC-9805, has been dosed for the first time in a patient with a KRAS-G12D-mutant solid tumor, marking the beginning of a phase 1/1b clinical trial (NCT06040541). The main purpose of this study is to assess safety & tolerability and antitumor activity of LY3962673 as monotherapy and in combination with other chemotherapy agents in participants with KRAS G12D-mutant advanced solid tumor types. The KRAS G12D mutation is present in nearly half of pancreatic adenocarcinomas (PDAC). HRS-4642 is a highly selective KRAS G12D inhibitor. Researchers are looking for ways to stop the actions of abnormal proteins made from the mutated KRAS gene. 18 In pancreatic cancer, there is a case report of tumor regression after therapy with KRAS G12D–specific TCRs. Of the therapies with KRAS G12D as a predictive biomarker, 2 are FDA-approved and 7 have NCCN guidelines in at least one clinical setting. 3% had at least one mutation in exon 2 of the gene. Sep 19, 2024 · However, there has been recent progress in this direction, with noncovalent KRAS G12D degraders based on KRAS G12D-selective inhibitors currently undergoing early clinical testing . The pharmacological inhibition of cyclin-dependent kinase (CDK) was as well of great clinical interest in the past years, and the Feb 12, 2021 · KRAS is being divided into subsets, such as KRAS G12C, G12D and G12R. 9% of non-small cell lung cancer cases. DCR-MYC Mar 22, 2024 · Abstract. In contrast, G12C was the most common KRAS mutation in NSCLC (35. With inhibitors to KRAS-G12D now entering clinical trials, understanding the biology of KRAS-G12D cancers, and iden … Aug 24, 2023 · Researchers at The University of Texas MD Anderson Cancer Center have uncovered a functional role for KRAS mutations in pancreatic cancer and rapidly translated these findings into a novel therapeutic approach combining a KRAS G12D inhibitor with immune checkpoint inhibitors for early- and late-stage KRAS G12D-mutant pancreatic cancer. Among KRAS mutations, KRAS G12D is the most frequent driver mutation and is found in approximately 34% of patients with pancreatic ductal adenocarcinoma (PDAC), 12% of patients with colorectal cancer (CRC), 4% of patients with lung adenocarcinoma, and in a subset of patients with other solid tumors. We would like to show you a description here but the site won’t allow us. 3 in progress, 2 open to eligible people . 9% [79/220]), followed by G12D (16. In this work, we provide preclinical validation for a single small-molecule degrader, targeting 13 of the 17 most prevalent KRAS mutants, that illuminates a new pan Feb 27, 2024 · Multi-KRAS inhibitor: Ph1 in KRAS G12D+ve cancers: Said to be G12D-preferring; Quanta also developing G12V-preferring multi-KRAS inhibitor QTX3544 (preclinical) Unnamed: Lilly: Pan-KRAS inhibitor: Preclinical: Poster at AACR-NCI-EORTC 2023; clinical trial planned 2024: Unnamed: BeiGene: Pan-KRAS inhibitor: Preclinical View Clinical Trials for KRAS G12V KRAS G12V serves as an inclusion eligibility criterion in 6 clinical trials, of which 5 are open and 1 is closed. All trials on the list are NCI-supported clinical trials, which are sponsored or otherwise financially supported by NCI. 19 Currently, there are multiple ongoing early-phase clinical trials evaluating TCRs in CRC, including NCT0610521 and NCT06043713 for KRAS Dec 15, 2023 · This noncovalent compound targets both the inactive and active form of KRAS G12D, the most common KRAS mutation in PDAC and colorectal cancer. Many types of cancer are caused by changes, or mutations, in a gene called KRAS. The reason for this bias is unclear, although evidence suggests that the KRAS G12R oncoprotein has distinct biochemical properties and is less Mesenchymal Stromal Cells-derived Exosomes with KRAS G12D siRNA Description This phase I trial studies the best dose and side effects of mesenchymal stromal cells-derived exosomes with KrasG12D siRNA (iExosomes) in treating participants with pancreatic cancer with KrasG12D mutation that has spread to other places in the body. Jan 24, 2023 · This study characterizes the real-world clinico-genomic landscape of patients with KRAS G12D-mutated PDAC to inform ongoing therapeutic development and clinical trial design. Abstract. NCI’s basic information about clinical trials explains the types and phases of trials and how they are carried out. Methods: This is a first-in-human, multicenter, open-label phase 1 study in adult patients with advanced solid tumors with KRAS G12D mutations, without prior direct KRAS inhibitor treatment (NCT06227377). The Triple meeting title promises data in PDAC, so there should be a chance for a cross-trial comparison against ASP3082. Expansion cohorts in pancreatic, colorectal, and lung cancer are part of the design of this trial. Apr 4, 2023 · Abstract. QTX3034 is a non-covalent, potent, orally bioavailable, and allosteric multi-KRAS inhibitor with G12D-preferring activity. Jan 9, 2024 · Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. In two pancreatic cancer cell lines bearing the KRAS G12D mutation (PANC-1 and Panc 04. May 11, 2024 · The NCT01833143 phase II single-center clinical trial of bortezomib subcutaneously administered to patients with advanced NSCLC a phase 2 trial of bortezomib in patients with KRAS G12D-mutant Oct 7, 2022 · The usefulness of targeting KRAS G12D will be amplified if MRTX1133 (or other inhibitors) successfully advances to clinical trials and is able to demonstrate substantial anti-cancer efficacy. It is given intravenously (by vein) through a central venous port on a weekly schedule. Nov 15, 2021 · Another study has shown that KRAS (G12D) AMG510 is the first small molecule inhibitor specifically targeting KRAS (G12C) to enter clinical trials (NCT03600883), 3 days ago · Quanta Therapeutics announced advancements in its KRAS-directed drug candidates, including FDA IND clearance for QTX3544, a G12V-preferring multi-KRAS inhibitor, allowing for a Phase 1 clinical trial. Epidemiologically, KRAS G12D mutation is more likely to occur in patients with NSCLC who do not smoke. However, no results of KRAS G12D inhibitors from any clinical trials have been reported yet. The clinical trials on this list are studying kras g12d inhibitor incb161734. ymrm jktblx nota oofhjd duuv acuruq fxgq hvykdqvep igmui xglhvxn