Clayton

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 evaluating the safety and tolerability of MK-4716, a drug being studied alone or in combination with other treatments, in people with certain advanced or metastatic solid tumors that have a KRAS alteration. This phase 1, open-label study focuses on participants with locally advanced unresectable or metastatic solid tumors or metastatic non-small cell lung cancer. The study aims to understand how well MK-4716 is tolerated and its safety profile, including monitoring for dose-limiting toxicities and adverse events. Participants receive MK-4716 orally, either as monotherapy or combined with pembrolizumab or cetuximab, both given by intravenous infusion. Different study arms target specific patient groups: one arm includes MK-4716 alone or with cetuximab for solid tumors with KRAS alteration, while another arm combines MK-4716 with pembrolizumab for untreated metastatic non-small cell lung cancer with KRAS alteration. The study includes a dose escalation phase to determine safe dosing. Throughout the study, participants are regularly monitored for side effects, adverse events, and any reasons for stopping the study treatments over approximately five years. Researchers track dose-limiting toxicities within about 28 days of treatment and assess safety, pharmacokinetics, and efficacy. Participants must have measurable disease and the ability to take oral medication to join the trial.

Researchers are evaluating treatments for breast cancer that is hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-), specifically in cases where the cancer is either locally advanced and cannot be removed by surgery or has spread to other parts of the body (metastatic). The study aims to determine if patritumab deruxtecan (also called HER3-DXd or MK-1022) helps patients live longer overall or without the cancer growing compared to chemotherapy or trastuzumab deruxtecan. This is a Phase 3 clinical trial focusing on this particular type of breast cancer. Participants receive one of several treatments: patritumab deruxtecan through intravenous infusion, chemotherapy options like paclitaxel or nab-paclitaxel via IV, oral capecitabine tablets, liposomal doxorubicin via IV, or trastuzumab deruxtecan via IV infusion. The study compares the effects of patritumab deruxtecan alone to the treatment chosen by the physician. Treatments are administered according to standard dosing schedules during the trial. During the study, participants are monitored for how long they live without the cancer progressing (up to about 45 months) and overall survival (up to about 85 months). Researchers assess disease status through imaging and other evaluations. Participants have regular check-ups to monitor health, treatment effects, and any side effects. The study tracks treatment response and safety over the extended follow-up period to understand the benefits and risks of the therapies.

Researchers are investigating new treatments for people with high-risk, early-stage breast cancer, specifically targeting triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/HER2-negative breast cancer. These types have little or no HER2 protein and involve hormones like estrogen or progesterone. The study aims to evaluate if the addition of sacituzumab tirumotecan (sac-TMT), a targeted therapy, combined with pembrolizumab and chemotherapy can improve outcomes compared to pembrolizumab with chemotherapy alone. Participants receive treatments including sacituzumab tirumotecan, pembrolizumab, and chemotherapy drugs such as carboplatin and paclitaxel, all given by intravenous infusion. Rescue medications like antihistamines, acetaminophen, dexamethasone, or steroid mouthwash may be used as needed. The study is randomized and open-label, comparing sac-TMT followed by chemotherapy plus pembrolizumab to chemotherapy and pembrolizumab without sac-TMT. During the study, researchers will monitor participants up to about 30 weeks to assess the percentage of people with no remaining cancer cells at surgery. They will also follow participants for up to approximately 92 months to track event-free survival, meaning time without cancer growth, spread, or return. Participants will undergo imaging, clinical assessments, and laboratory tests to evaluate treatment effects and safety throughout the study.

Researchers are evaluating the effects of oral neflamapimod, a specific inhibitor of the enzyme p38 alpha kinase, on recovery after moderate to severe acute ischemic stroke. The study aims to determine whether neflamapimod can improve residual physical disability and cognitive dysfunction following such strokes. This is a Phase 2, double-blind, placebo-controlled clinical trial targeting adults who have recently experienced an ischemic stroke in the brain's anterior circulation. Participants will receive either neflamapimod capsules containing 40 mg of the active drug or placebo capsules that look identical but contain no active ingredients. The treatment will be administered over a 12-week period. The study compares motor recovery and other functional outcomes between the neflamapimod and placebo groups to assess the investigational drug's impact. During the study, participants will undergo various assessments including the Fugl-Meyer Assessment of Motor Recovery, the Timed Up and Go Test, and the National Institutes of Health Stroke Scale motor score. These evaluations will measure changes from baseline to Week 12 to track motor and cognitive recovery. Safety monitoring and adherence will be conducted through regular evaluations. The total participation period covers enrollment through the end of treatment at 12 weeks.

Researchers are evaluating the safety, tolerability, how the body processes the drug, and early antitumor effects of BG-C137, an antibody-drug conjugate targeting FGFR2b, alone and combined with other anticancer drugs in people with advanced solid tumors. This study includes two phases: Phase 1a focuses on dose escalation and safety, while Phase 1b involves dose expansion. The trial is sponsored by BeOne Medicines, formerly BeiGene. Participants receive BG-C137 through intravenous infusion. In combination groups, anticancer agents are given either intravenously or orally. Phase 1a includes monotherapy dose escalation, safety expansion, and combination dose confirmation and safety expansion. Phase 1b focuses on dose expansion. The study will determine the maximum tolerated dose, recommended doses for expansion, and overall response rates over approximately two years. During the study, participants will undergo evaluations including safety monitoring for adverse events, pharmacokinetic and pharmacodynamic assessments, and tumor response measurements using RECIST v1.1 criteria. Researchers will collect tumor tissue samples to assess FGFR2b expression and other biomarkers. Participants' physical function, organ health, and prior treatments will be reviewed. The total study duration may last up to about two years, with close monitoring of side effects and treatment effects throughout.

Researchers are conducting a first-in-human Phase 1a/1b study to evaluate BG-C0902, a fully humanized antibody-drug conjugate targeting EGFR and MET, linked to a topoisomerase 1 inhibitor. This study aims to assess its safety, tolerability, pharmacokinetics, pharmacodynamics, and initial antitumor effects in adults with advanced solid tumors that cannot be treated with curative intent or have no available treatment options. The trial is sponsored by BeOne Medicines, previously known as BeiGene. The study includes two phases: Phase 1a involves dose escalation and safety expansion, while Phase 1b focuses on dose expansion. BG-C0902 is given by intravenous infusion, either alone or combined with other therapies. Researchers will determine the maximum tolerated dose, dose-limiting toxicities, recommended doses for expansion, and overall response rates over approximately 24 months. Participants will undergo screening to confirm eligibility, including tumor tissue collection and measurable disease assessment. Throughout the study, safety and response will be closely monitored via laboratory tests, imaging, and clinical evaluations. The study tracks adverse events and pharmacokinetics, with follow-up lasting up to two years to evaluate treatment effects and safety outcomes.

Researchers are evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and early antitumor effects of BGB-53038, a pan-KRAS inhibitor, in people with advanced or metastatic solid tumors that have KRAS mutations or amplifications. The study also explores using BGB-53038 alone or combined with tislelizumab in nonsquamous non-small cell lung cancer and with cetuximab in colorectal cancer. This first-in-human, open-label, multicenter study has two phases: Phase 1a for dose escalation and safety expansion, and Phase 1b for dose expansion. Participants receive BGB-53038 orally. In combination groups, tislelizumab and cetuximab are given by intravenous infusion to participants with specific cancers. The study evaluates different doses to find the maximum tolerated dose, recommended doses for further study, and overall response rates over approximately two years. Throughout the study, participants are closely monitored for adverse events, treatment responses, and drug effects. Researchers collect data on safety, tolerability, and preliminary antitumor activity. The total study duration includes dose escalation, expansion phases, and follow-up assessments lasting up to about two years.

Researchers are evaluating IBI354, a recombinant anti-HER2 monoclonal antibody-camptothecin derivative conjugate, in adults with locally advanced unresectable or metastatic solid tumors. This Phase 1/2, open-label, multicenter study aims to determine the safety, tolerability, dose-limiting toxicities, maximum tolerated dose, maximum administered dose, and recommended Phase 2 dose of IBI354. The study also explores and confirms the drug's efficacy, safety, and tolerability in this patient population. Participants receive sequential doses of IBI354 during the study. The trial includes a Phase 1a dose-escalation period to establish dose limits and Phase 1b/2 periods enrolling subjects with specific solid tumors expressing HER2 to evaluate treatment effects. Dosing schedules and administration details are guided by safety and tolerability findings. The study drug is administered as an injection. Throughout the study, researchers monitor participants for serious adverse events and treatment-emergent side effects up to 30 days after the last dose. Dose-limiting toxicities are specifically assessed during the first 21 days of treatment in Phase 1a. Participants undergo evaluations including echocardiography to check heart function before drug administration. Safety, response, and tolerability are closely followed to understand the treatment impact and support future dosing decisions.

Researchers are conducting a Phase 1/2 study to evaluate the safety and tolerability of BDC-4182, an immune stimulating antibody conjugate, in patients with advanced gastric and gastroesophageal cancers. This first-in-human trial aims to find the recommended Phase 2 dose by gradually increasing doses and monitoring participants closely. The study focuses on patients with measurable metastatic or unresectable cancer who have already undergone prior standard treatments or cannot tolerate them. Participants will receive BDC-4182, which combines an anti-claudin 18.2 monoclonal antibody with a TLR 7/8 dual agonist, delivered as a single agent. The study includes a dose escalation phase where participants are enrolled in cohorts until the maximum tolerated dose is found. Additional participants may join backfill cohorts for further safety data or the expansion phase at the recommended dose level. Throughout the study, participants will undergo biopsies or tumor sample collection before enrollment. Researchers will monitor adverse events up to around two years, including serious and dose-limiting toxicities within the first 21 days. Organ function and other health assessments will be performed to ensure safety. The trial carefully tracks treatment effects and tolerability in this patient population over the course of the study.