Wilson

Researchers are evaluating the safety and effectiveness of rilvegostomig combined with platinum-based chemotherapy compared to pembrolizumab combined with platinum-based chemotherapy as a first treatment for patients with locally advanced or metastatic squamous non-small cell lung cancer mNSCLC whose tumors express programmed death-ligand 1 PD-L1. This Phase III global study focuses on patients with PD-L1 tumor cell expression of 1% or higher and aims to determine which treatment provides better overall and progression-free survival. Participants will be randomly assigned to one of two study groups one group will receive rilvegostomig plus carboplatin and either paclitaxel or nab-paclitaxel chemotherapy, while the other group will receive pembrolizumab plus the same chemotherapy options. Rilvegostomig and pembrolizumab are both given intravenously on Day 1 of each 21-day cycle, with chemotherapy given up to 4 cycles. Nab-paclitaxel may be administered on Days 1, 8, and 15 of each cycle. Treatment continues with rilvegostomig or pembrolizumab until disease progression or other criteria are met. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests to monitor organ function, and patient questionnaires about physical function and quality of life. Researchers will track overall survival, progression-free survival, response rates, and duration of response for up to approximately 6 years. Safety and immune response to rilvegostomig will also be evaluated. Participants will be closely monitored throughout the treatment and follow-up periods.

Researchers are conducting a Phase 1a1b open-label study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of PLN-101095 combined with pembrolizumab in adults with advanced or metastatic solid tumors. Participants must have tumors for which pembrolizumab is indicated and must show disease progression or relapse after at least three months of pembrolizumab treatment. The study includes consecutive dose-escalation and dose-expansion cohorts to explore different dosing levels and tumor types. The study has two main parts Part 1 uses a Bayesian optimal interval design for dose escalation with accelerated titration to test increasing doses of PLN-101095 combined with pembrolizumab, while Part 2 uses Simons two-stage design for dose expansion. Doses of PLN-101095 range from 250 mg twice daily up to 2000 mg twice daily or 1000 mg three times daily, given in combination with pembrolizumab administered intravenously every three weeks. Participants in expansion cohorts include those with non-small cell lung cancer, clear cell renal cell carcinoma, or tumor mutational burden-high solid tumors, receiving PLN-101095 as monotherapy or combined with pembrolizumab. Participants will be monitored for safety and tolerability from first dose through 16 weeks after treatment ends, and anti-tumor activity will be measured from first dose until disease progression or death. Pharmacokinetics of PLN-101095 will be assessed at specified time points. The study evaluates participants measurable lesions and organ function, with follow-up assessments for adverse events and treatment response. The total duration varies depending on treatment response and tolerability, with ongoing monitoring throughout the study period.

Researchers are evaluating the safety and tolerability of DB-1303BNT323 in adults with advanced or metastatic solid tumors that express HER2. This Phase 12a trial focuses on patients with tumors that are advanced, unresectable, recurrent, or metastatic and have limited or no standard treatment options. The study aims to identify the best dose and explore early signs of effectiveness in a variety of HER2-expressing cancers. The trial has two parts an initial dose-escalation phase using an accelerated titration followed by a classic 33 design to find the maximum tolerated dose MTD or recommended Phase 2 dose RP2D, and a dose-expansion phase to further assess safety, tolerability, and potential effects at the established dose. Participants receive DB-1303BNT323 by intravenous infusion once every three weeks Q3W at various dose levels. Some groups are randomized to receive different dose levels or combinations with other drugs like Pertuzumab, Ritonavir, or Itraconazole to study drug interactions and responses. During the study, participants will have regular assessments including monitoring for dose-limiting toxicities, adverse events, and serious adverse events using standard criteria up to about one year after treatment. Researchers will also evaluate tumor responses using RECIST 1.1 criteria and collect pharmacokinetic and pharmacodynamic data. Other evaluations include heart function tests, organ function, and overall health status. The study duration varies per participant, with follow-up visits extending up to one year post-treatment to monitor safety and treatment effects.

This trial is for adults with recurrent or metastatic head and neck squamous cell carcinoma HNSCC that has not been treated with systemic therapy before. The study compares the anti-tumor effects of amivantamab combined with pembrolizumab and carboplatin against pembrolizumab with 5-fluorouracil and platinum therapy carboplatin or cisplatin. Participants have HNSCC in the oral cavity, oropharynx, hypopharynx, or larynx but not nasopharynx or unknown primary tumor sites, and HPV status is considered for oropharynx cases. Participants are randomly assigned to one of two groups. One group receives pembrolizumab, amivantamab, and carboplatin, while the other receives pembrolizumab, 5-fluorouracil given as a 4-day infusion, and carboplatin or cisplatin. Treatments are given according to standard protocols for these drugs. The study is open-label and conducted across multiple centers. During the trial, participants will be monitored for overall survival and tumor response using established criteria up to about 3 years and 7 months. Additional assessments include progression-free survival, duration of response, quality of life questionnaires specific to head and neck cancer, and safety evaluations through adverse event and lab test monitoring. Blood samples will check amivantamab levels and antibodies. Participation involves regular visits for treatment and assessments throughout the study period.

Researchers are evaluating the effectiveness of amivantamab combined with either lazertinib or platinum-based chemotherapy in treating participants who have epidermal growth factor receptor mutated EGFRm non-small cell lung cancer NSCLC. This study focuses on advanced or metastatic NSCLC cases where standard curative treatments are not suitable. It aims to assess the antitumor activity of these treatment combinations in this patient population. Participants receive either amivantamab with oral lazertinib in 28-day cycles or amivantamab with intravenous chemotherapy consisting of carboplatin and pemetrexed in 21-day cycles. Treatment continues until disease progression, participant withdrawal, death, or investigator decision to stop treatment. The study is designed with two separate groups receiving these distinct treatment combinations. Throughout the study, participants will undergo assessments to monitor treatment effects and safety. Researchers will measure progression-free survival as the primary outcome up to 4 years and 6 months, along with secondary outcomes including dose adjustments, adverse events, overall survival, response rates, and duration of response. Participants are followed regularly during treatment to track these outcomes and manage any side effects until the studys completion.

Researchers are evaluating the safety, tolerability, preliminary effectiveness, and how the body processes efimosfermin in adults with metabolic dysfunction-associated steatohepatitis MASH and compensated cirrhosis showing stage F4 fibrosis. This study focuses on people diagnosed by liver biopsy with advanced but stable liver disease caused by metabolic problems. It aims to understand the impact of efimosfermin on this condition. Participants will be randomly assigned to one of three groups two groups will receive different doses of efimosfermin, and one group will receive a placebo. All treatments are given as subcutaneous injections once every four weeks. The study will last up to 100 weeks for safety and includes monitoring drug levels in the blood up to 21 weeks. The comparison of two doses of efimosfermin versus placebo allows researchers to assess tolerability and drug behavior. During the trial, participants will be regularly assessed for any treatment-related side effects and have blood samples taken to measure drug concentrations. Researchers will monitor adverse events from the first day through 100 weeks. The study includes multiple visits for injections and evaluations. Participants will be observed closely to gather information on safety and the drugs effects over time, with the total duration extending up to nearly two years.

Researchers are evaluating the addition of Tersolisib LY4064809STX-478 to other anti-cancer drugs as a first treatment for adults with advanced hormone receptor-positive HRhuman epidermal growth factor receptor 2-negative HER2- breast cancer that has a PIK3CA mutation. This Phase 3 randomized, double-blind, placebo-controlled trial aims to understand the efficacy and safety of this combination compared to placebo, focusing on improving outcomes for patients with this specific genetic change. Participants receive LY4064809 orally in one of two doses combined with a CDK46 inhibitor such as Ribociclib, Palbociclib, or Abemaciclib and endocrine therapy ET administered orally or via intramuscular injection. The comparison group receives a placebo combined with the same CDK46 inhibitor and ET. The study includes two parts Part 1 explores dose optimization, and Part 2 evaluates the treatment combinations effectiveness and safety as a first-line therapy. During the study, participants will have regular assessments to monitor cancer response, progression, and safety over an estimated period of up to 5 years or more. Researchers will measure outcomes such as overall response rate, progression-free survival, duration of response, overall survival, and quality of life. Treatment continues as long as the cancer benefits without intolerable side effects. Safety monitoring, laboratory tests, and quality of life questionnaires are part of the participant involvement throughout the trial.

Researchers are evaluating the safety, tolerability, and clinical activity of an unconjugated belantamab antibody alone and in combination with other treatments for people with refractory multiple myeloma RRMM. This study includes participants who have had several prior therapies, including a proteasome inhibitor, lenalidomide, and an anti-CD38 monoclonal antibody. The trial has three parts focusing on different combinations and dosages to better understand how these treatments work in this condition. Participants will receive one of several treatments depending on the study part in Part 1, they receive escalating doses of the unconjugated belantamab antibody alone in Part 2, the antibody is combined with a fixed dose of belantamab mafodotin, given as separate drugs and in Part 3, the antibody is combined with a pomalidomide-dexamethasone standard care backbone. Treatment in Parts 1 and 2 continues until disease progression, after which participants may opt to receive belantamab mafodotin alone. During the study, participants are monitored for adverse events and dose-limiting toxicities, as well as changes in laboratory and vital signs parameters. Researchers also track ocular events using a specific visual acuity scale. The study measures treatment responses, including overall response rates and very good partial response rates, along with drug levels in the blood. Participants are followed for up to 52 months to assess treatment effects and safety under medical supervision throughout the trial.

Researchers are evaluating the use of dexamethasone mouthwash as a preventive treatment for stomatitis related to Datopotamab Deruxtecan Dato-DXd in patients with metastatic or inoperable locally recurrent breast cancer or advanced or metastatic EGFR-mutated non-small cell lung cancer. This Phase IV, open-label, single-arm study aims to describe how often and how severe grade 2 or higher stomatitis occurs in participants receiving this prophylactic mouthwash during the first 12 weeks of Dato-DXd treatment. Participants will receive dexamethasone 0.5 mg5 mL alcohol-free mouthwash, swishing 10 mL four times daily for about 2 minutes and then spitting it out without swallowing. They must avoid food or drink for at least 30 minutes after use. This mouthwash will be used throughout their standard care treatment with Dato-DXd. The study includes two groups one with breast cancer and one with lung cancer patients, enrolling about 100 participants total over 18 months. During the study, participants will be monitored for stomatitis incidence and severity up to 12 weeks after starting treatment, with additional assessments up to about 21 months for onset and resolution timing. Researchers will also track adherence to the mouthwash, any dose changes in Dato-DXd due to stomatitis, and overall safety. Follow-up for safety continues for 28 days after the last study dose, with various evaluations including clinical assessments throughout the treatment period.

Researchers are evaluating the efficacy and safety of BGB-43395 combined with letrozole compared to an investigators choice of cyclin-dependent kinase 46 inhibitors CDK46i combined with letrozole in patients who have advanced or metastatic hormone receptor positive HR and human epidermal growth factor receptor 2 negative HER2- breast cancer. This study focuses on patients who have not received prior systemic treatment for their advanced or metastatic disease. The trial is a phase 3, open-label, randomized study sponsored by BeOne Medicines. Participants will be randomly assigned to one of two treatment groups. One group will receive oral BGB-43395 plus letrozole, while the other group will receive one of the CDK46 inhibitors abemaciclib, palbociclib, or ribociclib combined with letrozole, both administered orally. Treatments will be given according to the investigators choice for the comparator group. The studys primary treatment period is expected to last up to approximately 4 years for progression-free survival assessment, with follow-up extending up to approximately 11 years for overall survival and safety monitoring. During the study, participants will attend regular visits for treatment administration and monitoring. Researchers will assess progression-free survival as the primary outcome, with additional measures including overall survival, response rates, duration of response, clinical benefit, and safety assessments. Quality of life will be evaluated using the European Organisation for Research and Treatment of Cancer EORTC questionnaires. Safety will be monitored from the first dose until 30 days after the last dose, with long-term follow-up lasting up to approximately 11 years. Total participation duration may extend over this period depending on individual outcomes and monitoring requirements.