Saint Albans

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 investigating treatments for women with recurrent endometrial cancer that expresses different levels of the HER2 protein. The study has two groups based on the tumor's HER2 score: Cohort 1 includes patients with HER2 IHC 1+ or 2+ who have previously received immune checkpoint inhibitors and platinum-based chemotherapy, while Cohort 2 includes patients with HER2 IHC 3+. The purpose is to compare the effectiveness and safety of the investigational drug BNT323 (also called DB-1303) against chemotherapy in Cohort 1 and to evaluate BNT323 alone in Cohort 2. The study also looks at how the drug affects the immune system, the body's handling of the drug, quality of life, and potential side effects. Participants in Cohort 1 are randomly assigned to receive either BNT323 via intravenous infusion or a chemotherapy drug chosen by the investigator (doxorubicin, paclitaxel, or docetaxel if paclitaxel is unsuitable). Treatment continues until the cancer progresses, unacceptable side effects occur, or the participant withdraws consent. Those in Cohort 2 receive BNT323 alone until disease progression or other discontinuation criteria are met. The study includes a screening period, a treatment period expected to last about six months, followed by safety monitoring, efficacy follow-up, and long-term survival follow-up lasting up to approximately 53 months. During the study, participants undergo regular assessments including imaging scans to measure tumor response by RECIST criteria, safety monitoring for adverse effects, and evaluations of quality of life. Researchers also study the pharmacokinetics of BNT323 and the immune response. The main outcomes measured are progression-free survival in Cohort 1 and objective response rate in Cohort 2. Safety follow-up ensures ongoing monitoring after treatment to evaluate longer-term effects and participant wellbeing.

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 a combination therapy using BNT324, a B7-H3 antibody-drug conjugate, with BNT327, a bispecific antibody targeting PD-L1 and VEGF, in people with advanced or relapsed small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). This two-part Phase Ib/II trial aims to find safe and effective dose levels and to assess the therapy's safety and clinical effects in different lung cancer groups, including treatment-nave and relapsed patients. The study uses a dose escalation design in Part 1 to establish two safe combination dose levels of BNT324 and BNT327. In Part 2, participants receive either the higher or lower recommended dose to determine the optimal dose for further study. Some groups are randomized to one of the two doses, while others receive the highest dose based on prior results. Both drugs are given by intravenous infusion during the treatment period. Participants undergo screening before starting treatment, followed by treatment and safety monitoring. Researchers track dose-limiting toxicities, adverse events, dose adjustments, and treatment discontinuations up to 90 days after treatment ends or until new anticancer therapy starts. They also evaluate objective response rates up to 87 months after the first dose. Ongoing survival follow-up is included to assess long-term outcomes and safety.

Researchers are evaluating the pharmacokinetics and safety of a subcutaneous injection of durvalumab combined with recombinant human hyaluronidase (rHu) in adults with different types of solid tumors. This Phase I multicenter study aims to find a subcutaneous durvalumab dose that provides drug levels similar to intravenous durvalumab. The study includes participants with non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and limited-stage small cell lung cancer (LS-SCLC). The study is divided into two parts: Part 1 involves dose escalation with two planned dose levels of subcutaneous durvalumab in participants with NSCLC, HCC, or LS-SCLC. Part 2 focuses on dose expansion in participants with unresectable HCC, starting once the appropriate dose is identified. Durvalumab plus rHu is given under the skin, while intravenous durvalumab and tremelimumab are administered by infusion for some participants. Participants will be monitored from the first dose through approximately 17 months of durvalumab administration. Researchers will measure drug concentrations over time and the lowest concentration before the next dose. Participants will undergo assessments including safety evaluations, organ function tests, and disease measurements. The study also tracks side effects and overall drug exposure to evaluate safety and pharmacokinetics during treatment.

Researchers are evaluating the safety and effects of different doses of a new medicine called NNC0519-0130 on kidney function in adults with chronic kidney disease, some of whom may also have type 2 diabetes, and who are living with overweight or obesity. The study compares NNC0519-0130 with semaglutide, an existing medicine, and a placebo, which is a "dummy" treatment. This is a Phase 2 proof-of-concept and dose-finding study aimed at understanding how these treatments may reduce kidney damage. Participants will be randomly assigned to one of three groups receiving either NNC0519-0130, semaglutide, or placebo. All treatments are given by subcutaneous injection once weekly. The study treatment phase lasts up to 36 weeks, with assessments at weeks 12, 24, and 36 to monitor changes in kidney damage by measuring the urinary albumin-to-creatinine ratio. The overall study duration can be up to 43 weeks. During the study, participants will be regularly monitored through laboratory tests and clinical evaluations to assess kidney function and safety. Researchers will measure changes from the start of the study in the urinary albumin-to-creatinine ratio at multiple time points. Participants will also need to have stable doses of certain blood pressure medications before joining. Safety and treatment effects will be assessed throughout the study period.

Researchers are evaluating the maximum tolerated dose and safety of Anvumetostat, a PRMT5 inhibitor, given in combination with other therapies for adults with metastatic or locally advanced gastrointestinal, biliary tract, or pancreatic cancers that have a specific genetic deletion called homozygous MTAP-deletion. This phase 1b study aims to find the recommended dose while monitoring safety and tolerability in these patients. Participants will receive Anvumetostat orally along with other treatments including gemcitabine and nab-paclitaxel given intravenously, modified FOLFIRINOX (a combination of irinotecan, 5-FU, leucovorin, and oxaliplatin given IV), or RMC-6236 taken orally. The study includes different subprotocols for patients based on their cancer characteristics and previous treatments. Treatment schedules and combinations are carefully evaluated to determine the best dosing. During the study, participants will be closely monitored for side effects such as dose limiting toxicities, treatment emergent adverse events, and serious adverse events for up to about two years. Researchers will assess organ function, tumor response using RECIST criteria, and overall safety. The study involves tumor biopsies or archival tissue samples and various clinical assessments throughout the treatment and follow-up periods to ensure comprehensive evaluation of the drug combinations.

Researchers are evaluating the effect of a triple therapy inhaler called BGF MDI containing budesonide, glycopyrronium, and formoterol fumarate compared with a dual therapy inhaler called GFF MDI containing glycopyrronium and formoterol fumarate in people with Chronic Obstructive Pulmonary Disease (COPD) who have a higher risk of heart and lung problems. This Phase III randomized, double-blind, parallel group study takes place at multiple centers and focuses on cardiopulmonary outcomes in these patients. Participants receive either the BGF MDI 320/14.4/9.6 micrograms twice daily or the GFF MDI 14.4/9.6 micrograms twice daily. The treatments are inhaled using metered dose inhalers. The study compares these two therapies over time to see how they affect the time until the first severe heart or lung event occurs. The study design ensures that neither participants nor researchers know which treatment is given to reduce bias. During the study, participants will have regular visits to the study site or virtual visits to complete assessments. Researchers will monitor lung function, symptoms, and blood tests, including blood eosinophil counts and COPD assessment test scores. The main outcome measured is the time to the first severe cardiac or COPD event, with follow-up lasting up to three years. Safety and adherence to treatment will also be closely observed throughout the study period.

This research focuses on men with prostate cancer who have previously participated in an enzalutamide clinical study sponsored by Astellas or Medivation. It aims to gather long-term safety information from participants who continue to benefit from enzalutamide treatment. This is a Phase 2 open-label extension study designed to monitor ongoing treatment effects after the initial study has completed its primary analysis or evaluation period. Participants will continue their previous treatment regimens, which may include enzalutamide taken orally once daily. Some may also receive abiraterone acetate with prednisone or leuprolide acetate depending on their prior study enrollment. Dose adjustments are allowed with medical monitor approval. The first visit of this study should occur within seven days of the last visit of the prior study unless treatment is temporarily paused. Participants are asked to return to their study site every 24 weeks for safety reviews, including adverse event monitoring and medication checks. At visits every 12 weeks, participants return unused study drugs and receive new supplies if needed. Safety data, including all adverse events and serious adverse events, are collected from consent until study completion, which may last up to 96 months. The study follows local standard care guidelines and includes a post-marketing phase in South Korea.

Researchers are comparing how long participants with KRAS/NRAS and BRAF wild-type recurrent, unresectable, or metastatic colorectal cancer remain disease-free and their overall survival time when treated with two different regimens. This phase 3 study focuses on patients who have previously received chemotherapy. The study aims to evaluate progression-free survival and overall survival in participants receiving amivantamab plus FOLFIRI versus cetuximab or bevacizumab plus FOLFIRI. The study involves two treatment groups: one receiving amivantamab combined with chemotherapy drugs 5-fluorouracil, leucovorin calcium or levoleucovorin, and irinotecan (FOLFIRI), and the other receiving either cetuximab or bevacizumab with the same chemotherapy regimen. Participants will be randomly assigned to one of these treatment arms. The treatments will be administered according to protocol to assess their effects on the cancer. Participants will be monitored for up to 2 years and 1 month to measure progression-free survival through blinded independent central review and followed for overall survival for up to 4 years and 4 months. The study includes assessments of tumor response, safety, and other clinical evaluations. Tissue samples and detailed clinical data will also be collected. This comprehensive monitoring will help determine the comparative effectiveness of the treatment options over time.