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Researchers are studying whether combining calderasib, a targeted therapy for the KRAS G12C mutation, with subcutaneous pembrolizumab can treat non-small cell lung cancer (NSCLC). The study aims to determine if people receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a phase 3, randomized, open-label, multicenter clinical trial focusing on participants with advanced or metastatic nonsquamous NSCLC carrying the KRAS G12C mutation. Participants will receive one of two treatment combinations. One group will take calderasib orally along with subcutaneous pembrolizumab and berahyaluronidase alfa injections. The other group will receive subcutaneous pembrolizumab combined with chemotherapy drugs pemetrexed and a platinum-based drug, either carboplatin or cisplatin, administered by intravenous infusion. These treatments are given as first-line therapy, and the study evaluates their safety and effectiveness. During the study, researchers will monitor participants for progression-free survival, especially focusing on those with at least 1% PD-L1 tumor proportion score, for up to approximately 48 months. Participants will undergo regular assessments to track cancer progression and response to treatment. Safety and efficacy data will be collected throughout the study to understand how well the treatments work and their side effects over time.

Researchers are evaluating new treatment options for adults with locally advanced or metastatic colorectal cancer that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This study compares the safety and effectiveness of adding calderasib and cetuximab, both targeted therapies, to a standard chemotherapy regimen called mFOLFOX6. The goal is to see if this combination can help patients live longer without their cancer growing or spreading compared to current treatments that may include mFOLFOX6 with or without bevacizumab. The study has two parts. It involves treatment with calderasib taken as an oral tablet, cetuximab given according to standard procedures, and mFOLFOX6 chemotherapy combining oxaliplatin, leucovorin/levofolinate calcium, and 5-fluorouracil. Some participants may receive bevacizumab or a bevacizumab biosimilar as part of the comparison. The treatments are given following approved dosing schedules. This design allows researchers to assess the safety and tolerability of these drug combinations in treating this type of colorectal cancer with the KRAS G12C mutation. Participants will be monitored for side effects, treatment tolerability, and cancer progression over a period that may last up to about 44 months. Researchers will track outcomes such as how many participants experience dose-limiting toxicities or adverse events, how many stop treatment due to side effects, and progression-free survival time. Assessments include health evaluations, laboratory tests, and imaging to observe cancer status. This long-term follow-up aims to understand both safety and effectiveness of the treatment combinations.

Researchers are studying the safety and tolerability of budoprutug, a humanized monoclonal antibody that targets CD19 cells, in adults with primary membranous nephropathy (PMN). This Phase 2, open-label, multicenter trial focuses on patients who are anti-PLA2R antibody positive and continue to have proteinuria despite optimized RAAS inhibition. The study aims to evaluate three different intravenous dose regimens of budoprutug and their effects on this specific kidney condition. Participants will receive budoprutug through single intravenous doses on Day 1, Day 15, Day 169, and Day 183 within one of three sequential dose groups. Approximately 45 subjects will be enrolled, each receiving treatment according to their assigned dosing schedule. The study includes a follow-up period through Week 48, with additional monitoring for B-cell recovery as needed. During the study, participants will undergo safety assessments including monitoring for treatment-emergent adverse events up to 48 weeks. Researchers will also evaluate pharmacodynamics and preliminary efficacy through laboratory tests and clinical evaluations. Regular visits will include tests for kidney function, protein levels in urine, and blood cell counts, alongside other health assessments to ensure participant safety and gather data on how the drug affects the disease.

Researchers are evaluating the safety, how the body processes the drug, and the effectiveness of calderasib alone or combined with other treatments in adults with advanced solid tumors that have a specific KRAS G12C mutation. This is a Phase 1, open-label, multicenter study focusing on participants with this genetic mutation in their tumors, aiming to understand how calderasib works alone and with other drugs. Participants receive calderasib as an oral dose, and some may also receive other medications such as pembrolizumab through intravenous infusion, or drugs like carboplatin, pemetrexed, cetuximab, oxaliplatin, leucovorin, and 5-fluorouracil according to standard guidelines. The treatments may be given alone or in combination depending on the study arm, with dosing schedules following label instructions or protocol specifications. During the study, participants will be closely monitored for any dose-limiting toxicities and adverse events, including reasons for stopping treatment. Researchers will assess these effects for up to about 21 days for dose-limiting toxicities and up to 56 months for adverse events and treatment discontinuation. The study involves regular evaluations to track safety, tolerability, and how well the treatment works over time.

Researchers are evaluating the safety and effectiveness of calderasib combined with pembrolizumab as a first treatment in adults 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. This Phase 3 trial aims to test if the combination of calderasib and pembrolizumab improves progression-free survival and overall survival compared to pembrolizumab with a placebo. Participants receive oral calderasib tablets or placebo along with pembrolizumab given by intravenous infusion. The study compares these two treatment groups to see which provides better outcomes. Treatments continue during the study, and there are no additional interventions described beyond these drugs. During the trial, participants undergo regular assessments including scans and tests to monitor their cancer's progression and overall health. The main outcomes measured are progression-free survival for up to about 42 months and overall survival for up to about 56 months. Safety is monitored throughout, and participants are followed for several years to evaluate long-term effects of the treatments.

Researchers are investigating better treatments for people with advanced non-small cell lung cancer (NSCLC) that has specific genetic changes called HER2 mutations. Advanced NSCLC refers to lung cancers that have spread or are unlikely to be controlled with current treatments. HER2 is a protein that helps cells grow, and mutations cause abnormal HER2 leading to cancer growth. This Phase 3 study aims to compare the safety and effectiveness of a new drug, sevabertinib, against standard treatment in patients with this type of lung cancer. Participants will be randomly assigned to receive either sevabertinib tablets twice daily by mouth or standard treatment consisting of cycles of intravenous infusions including drugs like pembrolizumab, cisplatin, carboplatin, and pemetrexed every 21 days. Treatments continue as long as participants benefit without severe side effects or until they or their doctors decide to stop. Participants on standard treatment whose disease worsens may switch to sevabertinib and continue until progression, intolerable side effects, or decision to stop. During the study, participants will undergo imaging scans such as CT, PET, MRI, and X-rays to monitor cancer spread. Health checks include blood and urine tests, heart monitoring with ECG, and pregnancy tests for women. Researchers will ask about participants’ well-being and record any medical problems or side effects experienced. The main outcome measured is progression-free survival over up to about two years.

Researchers are conducting a Phase 3, global, randomized, open-label, multicenter trial to evaluate the safety and effectiveness of brelovitug (BJT-778) in treating chronic hepatitis delta virus (HDV) infection. The study aims to compare brelovitug treatment to delayed treatment in participants with chronic HDV infection. Approximately 80 participants will be enrolled and randomized into three groups to assess treatment outcomes. The study includes three arms: one group will receive brelovitug 300 mg by subcutaneous injection once weekly for 96 weeks; the second group will receive brelovitug 900 mg by subcutaneous injection once every 4 weeks for 96 weeks; the third group will initially delay treatment, attending clinic visits for 12 weeks, then start brelovitug 300 mg subcutaneously once weekly for 96 weeks. The study evaluates different dosing schedules and the effect of delayed treatment. Participants will be monitored for safety and efficacy, with the main outcome being the percentage of participants achieving a combined endpoint of virologic response and normalization of ALT levels at Week 24 compared to Week 12 in the delayed-treatment arm. The trial includes regular clinical visits, laboratory tests, and assessments over the treatment period to track response and safety. Total participation duration aligns with the 96 weeks of treatment after initial randomization or delay period.

Researchers are studying adults aged 18 to 60 who have suffered thoracic combat-related injuries causing acute chest pain. The trial compares two minimally invasive pain treatments, cryoablation and radiofrequency ablation, to see which better controls severe chest pain and improves recovery. Both methods target intercostal nerves responsible for transmitting pain signals, aiming to reduce pain intensity, opioid use, and improve breathing and daily functioning. The study is conducted at multiple centers in Ukraine and seeks to provide evidence on the safety and effectiveness of these treatments in this patient group. Participants will be randomly assigned to receive either cryoablation, which applies extreme cold to nerves, or radiofrequency ablation, which uses controlled heat. Both procedures are performed percutaneously with image guidance to target the nerves involved in pain transmission. The number of treated nerve levels depends on injury location and clinical assessment. These treatments are given along with standard trauma care, aiming to reduce pain, lower opioid medication needs, and support better respiratory function. Throughout the study, pain intensity is measured before treatment and at 4, 24, and 72 hours after the procedure using a numeric rating scale. Researchers will also monitor opioid use, mechanical pain sensitivity through Von Frey testing, and lung function using incentive spirometry. Questionnaires assess how pain affects daily activities, quality of life, and emotional health. Safety is closely monitored during and after the procedures, with any side effects recorded. The study collects detailed data to compare outcomes between the two treatments and understand factors influencing pain relief and recovery.

The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798

Researchers are studying pembrolizumab (MK-3475) as part of an "umbrella master protocol" to treat non-small cell lung cancer (NSCLC). This trial includes multiple substudies, each enrolling different groups of participants with NSCLC to evaluate investigational drugs alone or combined with pembrolizumab or with pembrolizumab plus chemotherapy. The study focuses on patients with stage IV NSCLC, including both squamous and nonsquamous types, and looks at tumor biomarkers such as PD-L1 expression and tumor histology status. The study involves several substudies with different designs, including Phase 1/2 and Phase 2 trials. Treatments may include pembrolizumab alone, pembrolizumab combined with chemotherapy, or pembrolizumab plus other investigational agents. Participants may receive these treatments either sequentially or concurrently. Tumor imaging using MRI or CT scans is performed, and tumor tissue may be collected if archival samples are not available. Blood samples will also be collected for genetic and biomarker analyses, including circulating tumor DNA. Participants will be monitored closely through tumor scans, tissue and blood sample collections, and assessments of tumor response using standardized criteria. Researchers will evaluate outcomes such as PD-L1 tumor expression levels and tumor histology status within about one month. The study also involves safety monitoring and follow-up to understand the effects of the treatments. Participants must have measurable disease and meet specific health criteria to take part in the study.