KRAS Mutation

Researchers are evaluating a combination of three drugsadagrasib, cetuximab, and cemiplimabto see if they can help control metastatic colorectal cancer CRC that has a specific KRAS G12C mutation and has progressed after at least one prior chemotherapy treatment. This phase 1b2 study aims to determine the objective response rate, as well as other key outcomes like duration of response, progression-free survival, overall survival, and safety of this drug combination. The study also explores how tumors adapt to this treatment and seeks biomarkers that predict response or resistance. Participants will receive the study drugs in two phases a Lead-In phase where adagrasib dosing will be tested at different levels to find the recommended dose, followed by an Expansion phase where patients will receive adagrasib at the chosen dose along with cetuximab and cemiplimab. Adagrasib is taken orally, while cetuximab and cemiplimab are administered intravenously. The study includes mandatory tumor biopsies at baseline and during treatment to assess treatment effects. During the study, participants undergo various assessments including regular monitoring of safety and adverse events, tumor measurements, and laboratory tests to evaluate blood counts and organ function. The trial plans to follow participants through to study completion, averaging about one year, to collect data on treatment effectiveness and side effects. Participants must comply with study requirements including contraception use if applicable and attend scheduled visits for evaluations and biopsies.

Researchers are evaluating the safety, tolerability, pharmacokinetics, and recommended phase 2 dose of D3S-002 given orally in adult patients with advanced solid tumors that have mutations in the mitogen-activated protein kinase MAPK pathway. This first-in-human study includes different parts assessing D3S-002 alone or combined with D3S-001 in patients with specific tumor types, including non-small cell lung cancer without certain genetic mutations. The study has two main parts Part 1 is a dose escalation phase where D3S-002 is given orally alone. Part 2 includes a dose escalation phase and a dose expansion phase where participants receive both D3S-002 and D3S-001 orally. Treatments are given in 21-day cycles, and doses are adjusted to find the recommended phase 2 dose. Participants will be monitored from the first dose up to 24 months, with assessments including adverse events, dose-limiting toxicities, and pharmacokinetic measurements such as drug concentrations in the blood. Tumor response will also be evaluated using standardized criteria. Safety, tolerability, and effectiveness measurements will be collected throughout the study, and participants may be followed for up to two years after starting treatment.

Researchers are investigating treatments for people with advanced solid cancers that have a specific genetic change called the KRASG12C mutation. This trial focuses on combining two drugs sotorasib, which is already approved and targets cancer cells with this mutation, and BAY3498264, a new drug that aims to block a related protein called SOS1. The studys main goal is to find out how safe BAY3498264 is when given with sotorasib and to determine the highest safe dose for this combination. Participants will first receive BAY3498264 alone for seven days, followed by treatment cycles of BAY3498264 combined with sotorasib every day. These cycles last 21 days each, and treatment continues as long as it is beneficial and safe, or until the cancer progresses or the participant or doctor decides to stop. The study includes three parts dose escalation to find the right dose, backfill cohorts to gather more safety and drug data, and expansion cohorts to explore further effects and safety. During the study, participants will have blood and urine samples taken and undergo imaging scans like CT, PET, MRI, and X-rays. Heart health will be checked using electrocardiograms, and participants overall health will be closely monitored. Researchers will measure side effects, drug levels in the body, and cancer response, with treatment effects evaluated regularly. The study runs until about mid-2027, with ongoing safety and effectiveness assessments throughout.

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 efficacy and safety of the combination of divarasib and pembrolizumab compared with pembrolizumab combined with pemetrexed and either carboplatin or cisplatin. This study focuses on adults with previously untreated, advanced or metastatic non-squamous non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The goal is to assess these treatments as first-line options in this specific lung cancer population. Participants will be randomly assigned to one of two groups. One group will take divarasib orally once daily and receive pembrolizumab through an intravenous infusion every three weeks. The other group will receive pembrolizumab, pemetrexed, and either carboplatin or cisplatin via intravenous infusions every three weeks. Treatment continues with these schedules, following the study protocol for up to approximately five years of follow-up. During the study, participants will have regular assessments to monitor their health and response to treatment. These include imaging and clinical evaluations to measure progression-free survival and overall survival for up to five years. Researchers will also track quality of life, symptom changes, treatment side effects, and adverse events using questionnaires and patient-reported outcomes. Safety monitoring and detailed evaluations will help understand the effects of the treatments over the study duration.

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 12 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 III 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.

Researchers are evaluating the safety, pharmacokinetics, and preliminary effectiveness of NST-628, an oral drug targeting the MAPK pathway, in adults with advanced solid tumors that have specific genetic mutations and have exhausted standard treatments. This Phase 1, open-label, multi-center study includes patients with tumors dependent on the MAPK pathway, such as melanoma and glioma, aiming to find a suitable dose and observe tumor responses. The study has two parts Part A involves dose escalation where increasing doses of NST-628 are given once daily in 28-day cycles to determine the maximum tolerated dose and the recommended dose for expansion. Part B involves dose expansion with several cohorts of patients harboring specific MAPK pathway mutations receiving the recommended dose to further assess safety and tumor response. Dose adjustments may be made based on observed effects. Participants will undergo regular assessments including safety evaluations, tumor response measurements using standardized criteria, and pharmacokinetic analyses throughout the study, which lasts about one year on average for primary outcomes and up to two years for survival monitoring. Tumor tissue samples are required, and patients will be followed until the last visit of the final participant. Safety, tumor response, progression-free survival, overall survival, and drug behavior in the body are key outcomes measured.