KRAS Mutation

Primary Objective • To determine the objective response rate of the adagrasib, cetuximab, and cemiplimab combination for treatment of advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy. Secondary Objectives * To estimate duration of response (DOR), progression free survival (PFS), and overall survival (OS) for the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy. * To estimate the safety and tolerability of the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy. Exploratory Objectives * To assess predictive biomarkers of response and resistance to the combination of adagrasib, cetuximab, plus cemiplimab. * To assess mechanisms of tumor cell adaptation upon treatment with the combination of adagrasib, cetuximab, plus cemiplimab. * To determine mechanisms of acquired resistance to the combination of adagrasib, cetuximab, plus cemiplimab. * To assess the effect of the combination of adagrasib, cetuximab plus cemiplimab on the immune tumor microenvironment. * To generate cell lines and participant derived xenograft (PDX) models from tumor samples.

Researchers are looking for a better way to treat people who have advanced solid cancers with a KRASG12C mutation. Sotorasib is a drug that targets cancer cells which contain mutated KRASG12C protein; it can stop the cancer cells from growing and can lead to their death. Sotorasib is already approved to be used by doctors. However, when sotorasib works, it normally only works for a period of time, after which the cancer starts to grow again, and the patient may need a different treatment. BAY3498264 is a drug that is currently under development. It is expected to prevent the activity of a protein called son of sevenless 1 (SOS1). The SOS1 protein works together with KRAS; by blocking the activity of SOS1 with BAY3498264, it is hoped that the benefit offered by treatment with sotorasib may be increased - for example, resulting in a longer or deeper response. The main purpose of this first-in-human study is to learn how safe BAY3498264 is when given together with sotorasib and what is the maximum dose of BAY3498264 that can be safely given to participants together with sotorasib. During the study, participants will receive the following treatments: * BAY3498264: participants will first receive BAY3498264 alone for seven days and then BAY3498264 in combination with sotorasib. These combination treatments will be given in cycles, each lasting 21 days. * Sotorasib: participants will receive a standard, approved dose of Sotorasib once every day with BAY3498264. The treatment will continue for as long as participants benefit from it without any severe medical problems or until they or their doctor decide to stop the treatment, or until their cancer starts to grow again despite the treatment (also called 'progression'). This study has 3 parts, the dose escalation part, the backfill part and the expansion part. During the study, researchers will collect blood, urine, and take imaging scans like CT, PET, MRI, and X-rays, and examine the participants' heart health using an electrocardiogram (ECG). Participants' health is monitored throughout the study.

This study is a single-arm, multicenter, open-label, basket-design, pivotal phase II trial targeting adult patients with locally advanced or metastatic solid tumors harboring the KRAS p.G12C mutation. The included populations are: * Patients with advanced pancreatic cancer who have progressed or are intolerant to prior gemcitabine-based chemotherapy regimens or FOLFIRINOX/mFOLFIRINOX/NALIRIFOX treatments. * Patients with other advanced solid tumors (excluding NSCLC and CRC) who have progressed after prior systemic therapies or are intolerant and lack satisfactory alternative treatment options. The study aims to evaluate the efficacy and safety of Glecirasib in these patient populations.

The goal of this clinical trial is to evaluate FMC-376 in participants with advanced solid tumors with KRAS G12C mutations. This clinical trial will be conducted in 3 parts: Phase 1A (Dose Escalation), Phase 1B (Dose Expansion), and Phase 2 (Cohort Expansion). Multiple dose levels in participants with advanced solid tumors will be evaluated.

The purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with KRAS G12C-mutated, advanced or metastatic non squamous non-small cell lung cancer (NSCLC).

The purpose of this study is to find out whether avutometinib is a safe treatment for advanced or recurrent solid tumor cancers in children and young adults. Researchers will look for the highest dose of avutometinib that is safe and cause few or mild side effects.

This is a first-in-human (FIH), multicenter, open-label, dose-escalation, and dose-expansion Phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of D3S-001 or combination therapy in subjects with advanced KRAS p.G12C mutant solid tumors. D3S-001 will be taken daily by oral administration in 21-day treatment cycles.

This is a multicenter, open-label, phase I/II study to explore the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of GFH375 in patients with advanced solid tumors harboring a KRAS G12D mutation.

The goal of this clinical trial is to learn if KQB365 works to treat advanced solid tumor cancer in adults. It will also learn about the safety of KQB365. The main questions it aims to answer are: * What is the safe dose of KQB365 by itself or in combination with cetuximab? * Does KQB365 alone or in combination with cetuximab decrease the size of the tumor? * What happens to KQB365 in the body? Participants will: * Receive KQB365 infusion weekly alone or in combination with cetuximab * Visit the clinic about 9 times in the first 6 weeks, and then once every week after that.

The study includes two parts, a dose escalation part (Part A) followed by a dose expansion part (Part B). Part A will estimate the maximum tolerated dose (MTD) in dose escalation cohorts in patients with advanced solid tumors for whom no standard therapy is available in order to establish the recommended dose for expansion (RDE). Successive cohorts of subjects will receive escalating doses of NST-628 orally once daily in 28-day cycles. Bayesian Optimal Interval (BOIN) method will be used for dose escalation. Once MTD is reached or dose escalation is stopped prior to reaching MTD and provisional RDE selected, the provisional RDE level will be expanded. If warranted by dose/toxicity/anti-tumor activity observations, additional, lower dose level(s) may also be expanded. Part B of the study will include up to 6 cohorts of approximately up to 30 subjects each with select MAPK pathway mutant solid tumors enrolled at the RDE in order to explore benefit from treatment as suggested by preclinical findings and will better define the safety profile of NST-628 at the RDE. Additional safety information gathered in Part B may be used to modify the dose recommended for future studies. The end of the study is the last visit of the last subject.