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Researchers are evaluating if combining the medicines calderasib and subcutaneous pembrolizumab can more effectively treat people with non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The study aims to find out whether patients receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a Phase 3 clinical trial focusing on first-line treatment for advanced or metastatic nonsquamous NSCLC. Participants are assigned to one of two groups. One group receives subcutaneous pembrolizumab plus berahyaluronidase alfa every 6 weeks for up to 18 cycles about 2 years along with oral calderasib until treatment discontinuation criteria are met. The other group receives the same pembrolizumab and berahyaluronidase alfa regimen plus chemotherapy with pemetrexed and either carboplatin or cisplatin infusions during the early cycles. Treatment continues based on individual response and tolerability. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess progression-free survival, overall survival, response rates, and quality of life using questionnaires and symptom scores over several years. Safety will be monitored through adverse event reporting. The trial lasts up to about 7 years with ongoing evaluation of health outcomes and side effects to understand the impact of these treatment combinations.

Researchers are studying treatments for locally advanced or metastatic colorectal cancer mCRC that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This trial aims to evaluate if adding the targeted therapies calderasib and cetuximab to the standard chemotherapy regimen mFOLFOX6 can provide better outcomes compared to mFOLFOX6 with or without bevacizumab. The study focuses on the safety and tolerability of these combinations and whether they can help people live longer without their cancer growing or spreading. Participants will be assigned to one of two groups. One group will receive calderasib orally, cetuximab every two weeks, and mFOLFOX6 chemotherapy including oxaliplatin, leucovorin or levofolinate calcium, and 5-fluorouracil every two weeks. The other group will receive mFOLFOX6 chemotherapy with or without bevacizumab every two weeks, based on the investigators decision. Treatments will continue until certain stopping criteria are met. During the study, participants will be monitored for side effects and treatment tolerance, with regular assessments of cancer progression. Researchers will measure outcomes such as dose-limiting toxicities, adverse events, progression-free survival, and overall survival. Quality of life will also be evaluated through questionnaires. The study may last up to several years, with monitoring continuing for safety and effectiveness throughout the treatment period and follow-up.

Researchers are evaluating new treatments for locally advanced non-small cell lung cancer NSCLC that cannot be surgically removed and has a specific gene mutation called KRAS G12C. This trial aims to find out if the combination of calderasib MK-1084 and durvalumab can help participants live longer without their cancer growing or spreading compared to durvalumab with a placebo after they have completed chemotherapy and radiation therapy. Participants will be randomly assigned to receive either calderasib along with durvalumab or a placebo along with durvalumab. Calderasib is taken by mouth as a tablet, and durvalumab is given as an intravenous infusion. This study is double-blinded, meaning neither the participants nor the researchers know who receives the active drug or placebo. The treatment period will be followed by long-term monitoring. During the study, participants will have various assessments including survival monitoring up to approximately 9 years, evaluations of adverse events, response rates, and quality of life questionnaires. Researchers will also collect tumor tissue samples for biomarker analysis. The main measurement is progression-free survival, checked for up to about 6 years. Participants health and side effects will be closely tracked throughout and after treatment.

Researchers are evaluating the safety and tolerability of three different dose regimens of budoprutug in adults with primary membranous nephropathy PMN who test positive for anti-PLA2R antibodies and continue to have proteinuria despite optimized RAAS inhibition. This Phase 2, open-label, multicenter study aims to assess the safety, pharmacodynamics, and early effectiveness of budoprutug, a humanized monoclonal antibody that targets CD19 to deplete specific cells through antibody-dependent cellular cytotoxicity. Participants will receive a single intravenous dose of budoprutug on Days 1, 15, 169, and 183 across three sequential dose groups. Approximately 45 subjects will be enrolled and treated with one of the three dose levels. The study includes an initial dosing period followed by extended follow-up to monitor B-cell recovery and other effects up to Week 48. During the study, participants will be closely monitored for adverse events and changes in various laboratory measures, including B cell counts, anti-PLA2R antibody levels, proteinuria, and kidney function. Researchers will evaluate safety outcomes up to Week 48 and assess pharmacokinetics such as plasma concentration and clearance. Follow-up visits will track participant health, treatment effects, and recovery over the course of the study.

Researchers are evaluating the safety, how the body processes the drug, and the effects of calderasib alone and in combination with other therapies in adults with advanced solid tumors that have a specific genetic mutation called KRAS G12C. This study focuses on participants with measurable disease and adequate organ function who have this mutation confirmed by tissue or blood testing. It is a Phase 1 trial aiming to understand treatment tolerability and effectiveness in this patient group. Participants receive different study treatments depending on their assigned group. Some receive daily oral escalating doses of calderasib up to 800 mg until the disease progresses or treatment stops. Others receive calderasib combined with pembrolizumab infusions every 21 days for up to about 24 months, sometimes along with other chemotherapy drugs like carboplatin, pemetrexed, cetuximab, oxaliplatin, leucovorin, and 5-fluorouracil, given according to standard dosing schedules. Dosing may be adjusted based on safety. The study includes several treatment arms with different combinations. During the study, participants undergo regular safety monitoring, including tracking dose-limiting toxicities and adverse events over approximately 56 months. Researchers measure treatment effects, such as tumor response and duration, and study how calderasib behaves in the body through blood tests at designated times during treatment cycles. Participants will be followed through multiple cycles lasting 3 or 4 weeks depending on the arm, with assessments continuing for up to about 56 months to capture long-term effects and safety.

Researchers are evaluating the effectiveness and safety of combining calderasib with pembrolizumab as the first treatment for people with locally advanced or metastatic non-small cell lung cancer NSCLC that has a specific KRAS G12C mutation and a PD-L1 tumor proportion score of 50% or higher. The study compares this combination to pembrolizumab with a placebo to see if it improves the time participants live without the cancer worsening and overall survival. Participants receive pembrolizumab through an intravenous infusion every 21 days for up to 35 cycles. They also take calderasib or a matching placebo by mouth daily until they meet criteria to stop treatment. The study is randomized and double-blind, meaning neither participants nor researchers know who receives calderasib or placebo. During the study, participants will have regular assessments to monitor cancer progression, overall survival, response rate, and quality of life measures through questionnaires. Safety will be closely monitored by tracking adverse events and treatment discontinuations. The study may last up to about 56 months, including follow-up to observe long-term outcomes and quality of life changes.

Researchers are evaluating treatments for people with advanced non-small cell lung cancer NSCLC that have specific genetic changes called HER2 mutations. This lung cancer has spread or cannot be controlled with current treatments. The study aims to compare how well a drug called sevabertinib works and how safe it is compared to standard treatment for this type of cancer. Participants will receive either sevabertinib tablets twice daily or standard treatment consisting of pembrolizumab combined with platinum-based chemotherapy given every 21 days by infusion. Those on standard treatment who experience disease progression may switch to sevabertinib. Treatment continues as long as participants benefit and do not have severe side effects or until they or their doctor decide to stop. During the study, participants will have imaging scans like CT, PET, MRI, and X-rays to monitor cancer spread. Doctors will also perform health checks including blood and urine tests, heart monitoring with ECG, pregnancy tests for women, and ask about symptoms or side effects. The main measure is progression-free survival assessed up to about 2 years, with additional outcomes related to survival, response rates, side effects, and quality of life followed up to 4 years.

Researchers are evaluating two minimally invasive procedures, cryoablation and radiofrequency ablation, for managing acute pain following thoracic injuries sustained during combat. This multicenter clinical trial in Ukraine aims to compare the effectiveness and safety of these treatments in reducing severe chest pain and improving recovery. Both methods target intercostal nerves responsible for pain transmission, with the goal of reducing pain intensity, opioid use, and improving respiratory function and quality of life. Participants will be randomly assigned to receive either cryoablation or radiofrequency ablation, performed using percutaneous, image-guided techniques. Cryoablation applies extreme cold to temporarily interrupt nerve conduction, while radiofrequency ablation uses controlled heat to modulate nerve function. The number of intercostal levels treated depends on the injury pattern, and both procedures are delivered alongside standard trauma care. Assessments occur before and after the procedures to measure pain relief and functional improvements. During the study, participants will have pain intensity measured at 4, 24, and 72 hours post-procedure using a verbal numeric rating scale. Researchers will also monitor opioid medication use, mechanical pain sensitivity via Von Frey testing, and pulmonary function through incentive spirometry. Quality of life and emotional well-being will be assessed with validated tools including the LANS scale, McGill Pain Questionnaire, and PHQ-9 depression screening. Safety monitoring will focus on immediate and early complications. The study spans acute treatment and follow-up periods to support improved pain management decisions in this patient group.

Researchers are evaluating the effectiveness and safety of pembrolizumab MK-3475 alone or combined with chemotherapy and investigational agents including vibostolimab MK-7684, boserolimab MK-5890, MK-4830, MK-0482, Ifinatamab Deruxtecan I-DXd, and HER3-DXd. This study focuses on treatment-naive adults with advanced Stage IV squamous or non-squamous non-small cell lung cancer NSCLC. It is part of a larger pembrolizumab umbrella master protocol called KEYMAKER-U01. Participants receive pembrolizumab intravenously every three weeks, combined with chemotherapy agents like carboplatin, paclitaxel, or pemetrexed depending on cancer type and investigational agents according to their assigned study group. Initial treatment cycles last about 12 weeks followed by maintenance therapy continuing up to approximately two years. Some groups receive doses of investigational agents at different intervals, and treatments may escalate or stop based on disease progression or side effects. During the study, participants undergo various assessments including tumor response evaluations using RECIST 1.1 criteria, safety monitoring for adverse events, and laboratory tests to measure drug concentrations. Regular visits occur throughout treatment for monitoring effects and side effects. The studys main outcomes include measuring objective response rates, adverse events, treatment discontinuations, and dose-limiting toxicities over periods up to 27 months. Participants may remain in the study for up to about two years or longer depending on treatment duration and follow-up requirements.

Researchers are conducting an umbrella master protocol study to evaluate pembrolizumab MK-3475 in the treatment of non-small cell lung cancer NSCLC. This study includes multiple substudies that enroll different groups of NSCLC participants, covering various stages and treatment histories. The study aims to investigate the combination of pembrolizumab with other investigational agents and chemotherapy in different NSCLC populations. Participants may undergo tumor imaging using MRI or CT scans, tumor tissue collection if no archival samples are available, and blood sample collection for detailed genetic and biomarker analysis. The substudies involve treatment-naive patients, previously treated patients, and those with specific genetic mutations, with therapies administered alone or in combination in rolling arms. During the study, participants are screened and evaluated through imaging and tissue collection procedures. Researchers will measure outcomes such as PD-L1 tumor expression levels and tumor histology status within approximately one month. The study involves detailed monitoring of tumor characteristics and biomarkers to understand treatment responses, with participation potentially lasting up to several years until study completion.