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... that no competing interests exist. Funding: See page 21 Received: 09 September 2018 Accepted: 25 February 2019 ... Life.41861 23 of 25 Research article Neuroscience Kriegeskorte N, Kievit RA. 2013. Representational geometry ...
spectral-signature-and-behavioral-consequence-of-spontaneous-shifts-of-pupil-linked-arousal-in-human.pdf
... that no competing interests exist. Funding: See page 21 Received: 10 March 2021 Accepted: 27 August 2021 Published ... page Research article Neuroscience Podvalny et al. eLife 2021;10:e68265. DOI: https ...
A Platform Study of RAS(ON) Inhibitor Combinations in Patients with RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)
This study is designed to test how effective a new drug called AZD0486 (BITE for CD19) is for patients relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) who have already tried at least 1-2 other treatments. This study has three parts: Part A will test increasing doses of AZD0486 to find a dose with few side effects; Part B will test up to two doses from Part A to decide the best dose to use in the next phase; and Part C will use the best dose from Part B to see how well it works in more patients. AZD0486 will be given as an IV infusion on certain days of each 28-day cycle, with close monitoring for side effects. Side effects and effectiveness will be checked regularly, and the study will continue until enough data is collected to understand how well AZD0486 works and how safe it is.
A Multicenter Open-Label Study of RMC-6236 in Patients with Advanced Solid Tumors Harboring Specific Mutations in RAS
A Multicenter Open-Label Study of RMC-6236 inPatients with Advanced Solid Tumors Harboring Specific Mutations in RAS
A Phase 1/2 Multicenter Open-Label Study to Evaluate the Safety Tolerability and Preliminary Antitumor Activity of TNG462 in Combination with Other Agents in Patients with Pancreatic or Non-Small Cell Lung Cancer with MTAP Loss and RAS Mutation
This Phase 1/2 study will determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236 or RMC-9805.Overall, the study comprises a dose escalation phase and a dose expansion phase.
A Randomized Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer
This is a phase 3 study testing and comparing if study medicine amivantamab (monoclonal antibody) in combination with mFOLFOX6 or FOLFIRI (chemotherapy) is more beneficial than another medicine called cetuximab (Monoclonal antibody) in combination with mFOLFOX6 or FOLFIRI for patients whose colorectal cancer has spread from the primary location and that the tumor has KRAS/NRAS and BRAF wild-type genes. Patients will be divided into two groups. One group will receive amivantamab together with mFOLFOX6 or FOLFIRI, and the other group will receive cetuximab and mFOLFOX6 or FOLFIRI. All participants will have special scans taken to see if the study treatment is changing their tumor size and that the cancer is not progressing. The study team will collect blood samples from all patients to see how their bodies are responding to these medicines and whether antibodies to the study medicine are formed. Genetic testing will be done on blood and tumor samples in the hope of further helping patients. All patients will be monitored for side effects and safety throughout the study.
A Randomized Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wildtype Recurrent Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy
This is a randomized, open-label, active-controlled, parallel-group, multicenter, interventional, Phase 3 study of amivantamab and FOLFIRI compared with cetuximab or bevacizumab (investigator’s choice) and FOLFIRI in participants who have recurrent, unresectable or metastatic CRC that is KRAS/NRAS and BRAF WT.Participants must have received and radiographically progressed on or after fluoropyrimidine- and oxaliplatin-based chemotherapy, with or without anti-VEGF treatment, and must not have received prior irinotecan-based chemotherapy in the metastatic setting, anti-EGFR therapy, or anti-MET therapy.The screening period will be up to 28 days prior to randomization. The treatment period will begin on Cycle 1 Day 1 and continue as 28-day cycles. Participants will receive study treatment until radiographic disease progression by BICR or other discontinuation criteria are met. Participants will then be followed for survival, subsequent anticancer treatment, and disease status. Participant safety and study conduct will be monitored throughout the study.Following the final analysis of OS, participants who continue to benefit from study treatment, as determined by the investigator, may continue to receive access to study treatment(s), either via an open-label or long-term extension rollover study or any other post-trial access program, when available and permitted by local regulations.
A Phase 1/2a Open-label Study of VS-7375 a KRAS G12D (ON/OFF) Inhibitor as Monotherapy and in Combination in Patients with Advanced KRAS G12D-Mutant Solid Tumors
VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D inhibitor. VS-7375 demonstrated potent inhibition of KRAS G12D-mutated-dependent signal transduction and cancer cell viability in vitro, as well as anticancer activity in human CRC and PDAC xenograft models alone and in combination with cetuximab. Collectively, the significant unmet medical need for treating tumors that harbor KRAS G12D mutations and the nonclinical results with VS-7375 strongly support a rationale for its development in patients with KRAS G12D-mutated cancers.VS-7375 is currently in clinical development in China under the name GFH375 by GenFleet Therapeutics Technology Co., Ltd (Shanghai, China). A first-in-human (FIH) clinical study of VS-7375 (Study GFH375X1101; NCT06500676) is ongoing as a multiphase study in China targeting patients with advanced KRAS G12D-mutated solid tumors, including NSCLC, PDAC, and CRC. The Phase 1 portion of that study involves dose escalation using a Bayesian optimal interval (BOIN) design to evaluate safety, tolerability, and pharmacokinetics (PK) across a range of doses, with initial endpoints focused on evaluating adverse events (AEs) and dose-limiting toxicities (DLTs). As of 17 January 2025, the 750 mg daily dose has been cleared for DLTs, and Study GFH375X1101 remains ongoing in the dose finding stage for patients with KRAS G12D-mutated cancers in China.This study is designed to evaluate the safety, tolerability, preliminary anticancer activity, and PK of VS-7375 in participants with advanced solid tumors harboring a KRAS G12D mutation outside China. The study will be conducted in 4 parts: Part A (single-agent dose escalation),Part B (single-agent dose expansion), Part C (VS-7375 combination dose escalation), and Part D (VS-7375 combination dose expansion).
A Phase 1/1b Open-label Multicenter Study to Investigate the Safety Tolerability Pharmacokinetics and Antitumor Activity of KIN-2787 in Participants with BRAF and/or NRAS Mutation-positive Solid Tumors
This is a 2-part, open-label, multicenter, dose escalation and dose expansion study in participants with rapidly accelerated fibrosarcoma, homolog B (BRAF) mutation-positive and/or neuroblastoma RAS (NRAS) mutation-positive tumors designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of KIN-2787, a pan-rapidly accelerated fibrosarcoma (RAF) small molecule kinase inhibitor; to determine a recommended Phase 2 dose (RP2D) of KIN-2787 for further clinical development; and to assess the objective response to KIN-2787 therapy alone and in combination with binimetinib, a mitogen-activated protein kinase (MEK) inhibitor.
A Phase 1/2 Study of LY3537982 in Patients with KRAS G12C-Mutant Advanced Solid Tumors
Study LOXO-RAS-20001 is a first-in-human, multicenter, open-label Phase 1/2 study to evaluate the safety, tolerability, and preliminary efficacy of oral LY3537982 as monotherapy and as part of combination therapy in patients with KRAS G12C-mutant advanced solid tumor types, including but not limited to NSCLC and CRC.This study includes 2 parts, Phase 1a dose escalation (Part A) followed by a Phase 1b dose expansion (Part B-E). The Phase 1a dose escalation LY3537982 monotherapy cohort will enroll any eligible patient with KRAS G12C-mutant advanced solid tumor. Once the LY3537982 monotherapy RP2D (RP2DM) is established, Phase 1b dose expansion will begin and include 10 cohorts (NSCLC, Cohorts B1–B6; CRC, Cohorts C1–C2; other solid tumors [except NSCLC and CRC], Cohort D1; KRAS G12C-mutant advanced NSCLC who have previously been treated with a KRAS G12C inhibitor, Cohort E1) to further evaluate safety and clinical activity.KRAS G12C mutations will be identified through standard of care testing as routinely performed at each participating site utilizing material collected prior to patient consent to this protocol. Molecular assays utilized for enrollment are required to be performed in Clinical Laboratory Improvement Amendments (CLIA), International Organization for Standardization/International Electrotechnical Commission (ISO/IEC), College of American Pathologists (CAP), or other in a similarly certified laboratory.