KRAS Mutation

Researchers are studying whether the combination of three drugs—adagrasib, cetuximab, and cemiplimab—can help control metastatic colorectal cancer that has a specific KRAS G12C mutation and has progressed after at least one prior chemotherapy treatment. This multicenter trial includes participants with advanced disease who have measurable tumors and have met certain health criteria. The study is a Phase 1b/2 trial aiming to find the response rate, safety, and other outcomes of this drug combination. Participants will receive adagrasib orally, with the dose determined during a Lead-In phase where two different doses are tested for tolerability. Following this, in the Expansion phase, participants will receive the recommended dose of adagrasib. Cetuximab and cemiplimab are given intravenously alongside adagrasib. The study involves treatment cycles and includes mandatory biopsies to understand how the drugs affect the tumor and immune environment. During the trial, participants will undergo safety monitoring for adverse effects over about a year. Researchers will assess tumor response, progression, and overall survival. Blood tests, scans, and biopsies will be performed to monitor health and study drug effects. Participants must be willing to comply with study procedures and contraception requirements. The study is led by M.D. Anderson Cancer Center and will last until March 2029.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and appropriate dosing of D3S-002 in adults with advanced solid tumors that have mutations in the MAPK pathway. This first-in-human study aims to find the recommended phase 2 dose of D3S-002 given daily by mouth in 21-day cycles. The study includes adults with metastatic or locally advanced solid tumors or non-small cell lung cancer with specific genetic mutations and prior treatment history. The study has two main parts: Part 1 involves dose escalation of D3S-002 given orally as a single drug. Part 2a also involves dose escalation but tests D3S-002 together with another oral drug, D3S-001. Part 2b is a dose expansion phase where the combination of D3S-002 and D3S-001 is further evaluated. Both drugs are taken by mouth, and participants receive treatment cycles lasting 21 days each. Participants will be monitored for adverse events starting from the first dose until 30 days after their last dose, with ongoing assessments up to 24 months. Researchers will measure drug levels in the blood, responses to treatment using specific tumor evaluation criteria, and progression-free survival. Safety, tolerability, and pharmacokinetics are closely tracked throughout the study. Participants must adhere to study visits and provide tumor and blood samples for genetic analysis when required.

Researchers are investigating treatments for people with advanced solid tumors that have a specific genetic change called the KRASG12C mutation. This trial studies BAY3498264, a drug designed to block a protein called SOS1 that works with KRAS, alongside sotorasib, an already approved drug targeting KRASG12C. The goal is to find out how safe BAY3498264 is when combined with sotorasib and to determine the highest safe dose of BAY3498264 for patients. Participants will start by receiving BAY3498264 alone for seven days, followed by cycles of BAY3498264 combined with sotorasib every 21 days. Sotorasib is taken once daily at a standard approved dose. The study has three parts: dose escalation to find the best dose, backfill cohorts to gather more safety and drug data, and expansion cohorts for additional testing. Treatment continues as long as it helps without serious problems or until cancer progresses or the patient or doctor decides to stop. Throughout the study, participants will have blood and urine samples collected and undergo imaging scans like CT, PET, MRI, and X-rays. Heart health is monitored using electrocardiograms. Researchers will track safety by recording side effects, measure drug levels in the body, and assess cancer response regularly. Monitoring continues through treatment cycles and after the last dose to ensure participant safety and treatment effects are carefully observed.

Researchers are studying adult patients with locally advanced or metastatic solid tumors that have a specific KRAS p.G12C mutation, focusing on pancreatic cancer and other solid tumors that have progressed after prior treatments or are intolerant to them. The trial aims to evaluate the safety and effectiveness of the drug Glecirasib in these patients. This is a pivotal, single-arm, open-label phase II trial involving multiple centers. Participants will receive Glecirasib orally at a dose of 800 mg once daily in cycles of 21 days. Treatment will continue until the disease progresses, intolerable side effects occur, or the participant withdraws for other reasons. The study includes patients with advanced pancreatic cancer who have not responded to certain chemotherapy regimens or patients with other solid tumors excluding NSCLC and CRC who have limited treatment options. During the study, participants will be monitored for tumor response using independent radiological reviews according to RECIST 1.1 criteria over approximately 1.5 years. Researchers will assess outcomes such as objective response rate, duration and time to response, progression-free survival, disease control rate, and overall survival. Safety will be followed by tracking adverse events. The total observation period may extend up to about 2 years to fully evaluate these outcomes.

Researchers are evaluating the drug FMC-376 in adults with advanced solid tumors that have a specific KRAS G12C mutation. This clinical trial is designed in three parts: Phase 1A (dose escalation), Phase 1B (dose expansion), and Phase 2 (cohort expansion), to study various dose levels in participants with these tumors. The trial focuses on tumors that are locally advanced, unresectable, or metastatic, including types like non-small cell lung cancer, colorectal cancer, and pancreatic cancer. Participants will receive FMC-376 orally as a daily capsule in 21-day cycles during the dose escalation, dose expansion, and cohort expansion phases. The study does not include placebo or blinded treatments. The trial aims to assess the safety, pharmacokinetics (how the drug is absorbed and processed), and clinical activity of FMC-376 at multiple dose levels. During the study, participants will be monitored closely for dose-limiting toxicities within the first 21 days and adverse events for approximately 24 months. Researchers will measure drug levels in the blood, response rates, duration of response, disease control, progression-free survival, and overall survival. Participants will undergo regular assessments including laboratory tests and evaluations to track safety and treatment effects throughout the study period.

Researchers are evaluating the effectiveness and safety of combining divarasib and pembrolizumab compared to pembrolizumab with pemetrexed and carboplatin or cisplatin for first-line treatment in adults with KRAS G12C-mutated advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). This phase III study focuses on patients who have not received prior systemic treatment for this type of lung cancer and aims to provide new options for this specific mutation. Participants are randomly assigned to one of two groups. One group receives an oral daily dose of divarasib along with pembrolizumab given by intravenous infusion every three weeks. The other group receives pembrolizumab combined with pemetrexed and either carboplatin or cisplatin, also administered intravenously every three weeks. Treatments continue according to the study schedule to assess how well each combination works and their safety profiles. Throughout the study, participants will be closely monitored for progression-free survival and overall survival for up to approximately five years. Additional assessments include tumor response, quality of life related to lung cancer symptoms, duration of response, and side effects reported by patients. Safety is also tracked by recording adverse events and their impact on daily activities. This comprehensive monitoring helps researchers understand the full effects of the treatments over time.

Researchers are evaluating the safety of avutometinib as a treatment for children and young adults aged 3 to 30 years with advanced or recurrent solid tumor cancers, including pediatric tumors with specific genetic alterations affecting the MAP kinase pathway and certain neurofibromatosis conditions. This phase 1 study aims to find the highest dose of avutometinib that is safe and causes few or mild side effects. Participants receive oral avutometinib twice a week, once daily, in cycles of three weeks on treatment followed by one week off, with each cycle lasting 28 days. The study uses a dose-escalation design, starting at Dose Level 1 and adjusting the dose based on the number of dose-limiting toxicities (DLTs) observed, to identify the maximum tolerated dose (MTD). During the study, participants will be closely monitored for safety over up to 12 months. Researchers will assess side effects and tolerability, and participants will undergo regular evaluations including clinical assessments and laboratory tests. The study carefully tracks adverse events and adjusts dosing to ensure participant safety throughout the trial.

Researchers are evaluating the safety, tolerability, how the body processes, and early effectiveness of a drug called D3S-001 alone or combined with other treatments in adults with advanced solid tumors that have a specific KRAS p.G12C mutation. This first-in-human, open-label Phase 1/2 trial aims to better understand these aspects in patients with progressing metastatic or locally advanced tumors. D3 Bio (Wuxi) Co., Ltd is leading this multicenter study to explore potential treatment options for this mutation type in cancer. Participants will receive D3S-001 daily by mouth in cycles lasting 21 days. The study includes several parts: Part 1 focuses on increasing doses of D3S-001; Parts 2 and 3a Arm C involve dose expansion with D3S-001 alone for selected cancer types; Part 4a is for dose optimization. Combination therapies are also studied in Parts 3a Arms A and B, and Part 3b, where D3S-001 is given with pembrolizumab, chemotherapy drugs (cisplatin plus pemetrexed or carboplatin plus pemetrexed), or cetuximab, all administered intravenously. During the trial, participants will be closely monitored for side effects and dose-limiting toxicities from the first dose through the treatment cycles. Researchers will collect blood samples to measure drug levels and track tumor response using standard criteria up to 24 months. Additional assessments include performance status, organ function tests, and imaging to measure tumor size. The study will continue until 30 days after the last dose, with ongoing evaluation of safety, drug behavior in the body, and preliminary treatment effects.

Researchers are evaluating GFH375 in adults with advanced solid tumors that have a KRAS G12D mutation. This open-label, phase I/II clinical trial aims to explore the safety, tolerability, how the body processes the drug, and early signs of effectiveness in this patient group. Participants will receive GFH375 orally at assigned dose levels and continue treatment until their disease progresses or they experience unacceptable side effects. The study has multiple phases: phase Ia focuses on safety and dose-limiting toxicities over 21 days and up to 24 months, phase Ib also monitors safety for up to 24 months, and phase II assesses overall tumor response over 24 months. During the trial, participants will undergo regular assessments including monitoring for adverse events, blood tests for drug levels, and tumor measurements using RECIST 1.1 criteria. The main outcomes measured are the frequency and severity of side effects, dose-limiting toxicities, and tumor response rate. The total participation can last up to 24 months with detailed safety and efficacy evaluations throughout.

Researchers are evaluating the safety and effectiveness of KQB365, alone and in combination with cetuximab or KQB198, in adults with advanced solid tumor cancers that have specific KRAS G12C or G12S mutations. The trial aims to find the safe dose of KQB365, see if it decreases tumor size, and understand how the drug behaves in the body. This study focuses on patients with unresectable or metastatic tumors who have no curative treatment options available. Participants will receive weekly infusions of KQB365 either alone or combined with intravenous cetuximab or oral KQB198. The study includes a dose escalation phase to find the recommended dose, followed by dose expansion phases to evaluate treatment effects. The trial is open-label and non-randomized, with multiple treatment groups receiving different drug combinations to assess safety and response. During the trial, participants will visit the clinic about nine times in the first six weeks and then weekly thereafter. Researchers will monitor adverse events, dose tolerability, tumor response using RECIST criteria, and drug levels in the blood. Outcome measures include the number of side effects, recommended phase 2 dose, objective response rate, survival, and disease control. Monitoring continues for up to 35 months to assess long-term safety and treatment effects.