Fairfax

Researchers are conducting a 2-part, phase 1/2 open-label trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of ODM-212 combined with anti-cancer therapies in adults with advanced solid tumors. The study includes participants with mesothelioma, pancreatic cancer, and advanced non-small cell lung cancer (NSCLC) with a KRAS G12C mutation. The trial aims to explore the effects of these treatments in patients who meet specific disease and treatment history criteria. The trial consists of a dose escalation phase followed by a dose expansion and optimization phase. Participants receive ODM-212 40 mg tablets and may also be treated with ipilimumab and nivolumab, gemcitabine and nab-paclitaxel, or sotorasib, depending on their cancer type and previous treatments. Treatment schedules vary: ipilimumab is given intravenously every 6 weeks, nivolumab every 3 weeks, nab-paclitaxel and gemcitabine are administered intravenously on days 1, 8, and 15 of 28-day cycles, and sotorasib is taken orally daily in 21-day cycles. Participants will be monitored for dose-limiting toxicities and adverse events throughout the study, which lasts on average 2 years. Assessments include tumor biopsies, disease measurements by RECIST criteria, and regular safety evaluations. The study tracks participants’ adherence to oral medication and monitors overall health and response to treatment to better understand treatment safety and effectiveness over time.

Researchers are studying whether calderasib alone or combined with cetuximab can treat advanced solid tumors in people who have the KRAS G12C mutation. This phase 2, open-label trial aims to find out how many participants respond to these treatments and to compare their safety and tolerability. Participants receive calderasib by mouth and cetuximab through intravenous infusion. The study includes people with locally advanced or metastatic solid tumors other than colorectal cancer, who have already undergone standard treatments. The trial monitors response and side effects over time as participants receive either calderasib alone or in combination with cetuximab. During the study, participants undergo regular assessments to measure tumor response and track any side effects or adverse events. Researchers record how many people experience treatment-related side effects and how many stop treatment due to these effects. The study follows participants for up to approximately 76 months to assess long-term outcomes and safety.

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 intismeran autogene combined with pembrolizumab to see if it can stop advanced melanoma, a type of skin cancer that has spread and cannot be removed by surgery, from growing or spreading. This Phase 2 study compares this combination to pembrolizumab with a placebo, aiming to find out if the new treatment helps people live longer without cancer progression. Immunotherapy, which helps the immune system fight cancer, is a standard treatment for advanced melanoma, and intismeran autogene is designed to boost the immune response against a person's specific cancer. Participants receive either intismeran autogene or a placebo through intramuscular injection, along with pembrolizumab given as an intravenous infusion. The study is randomized, double-blind, and controlled, meaning neither participants nor researchers know who gets the active treatment or placebo. This design helps to better understand the effects of intismeran autogene when combined with pembrolizumab. During the study, researchers will monitor participants for up to about 36 months to measure progression-free survival, which means the length of time participants live without the cancer worsening. Assessments include imaging scans to track tumor changes, tumor tissue collection for biomarker analysis, and documentation of any side effects. Participants may also have their mutation status checked and will be observed for safety throughout the study period.

Researchers are evaluating the safety and preliminary effectiveness of T3011, a treatment given directly into tumors, alone and combined with pembrolizumab, an intravenous medication, in adults with advanced or metastatic solid tumors. This Phase 1/2a open-label study focuses on several types of cancers including melanoma, head and neck squamous cell carcinoma, sarcoma, cutaneous squamous cell carcinoma, and non-small cell lung cancer. The study aims to find the best dose of T3011 and understand its safety when used alone or with pembrolizumab. The study begins with a Phase 1 dose escalation to test increasing doses of T3011 using a 3+3 design. After determining the recommended dose, Phase 2a Part 1 will evaluate T3011 alone in different cancer types across multiple arms, while Phase 2a Part 2 will assess the combination of T3011 with pembrolizumab in participants with metastatic non-small cell lung cancer. T3011 is given as an intratumoral injection up to 4mL every two weeks, and pembrolizumab is given intravenously every three weeks when combined. A rollover arm allows participants whose disease progresses on T3011 alone to receive the combination treatment. Participants will be closely monitored for safety and treatment effects for up to two years from the first dose of T3011. Assessments include tumor measurements, biopsies, laboratory tests, and evaluation of adverse effects. The study records the tolerability of escalating doses and the combination treatment, tracking disease progression and response. Participants must attend scheduled visits for injections, monitoring, and evaluations throughout the study period.

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 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 LY3884961, a genetic therapy using a non-replicating viral vector, in adults with peripheral symptoms of Gaucher Disease, a rare genetic disorder. This Phase 1/2 open-label study aims to find safe dose levels and assess the treatment's safety and tolerability over a long period. The study includes patients with confirmed GBA1 gene variants who have been on stable treatment for at least two years. Participants will receive a single intravenous dose of LY3884961. The study starts with three dose-finding groups, each including three patients, followed by an expansion group with up to six patients. After dosing, the first 18 months focus on monitoring safety, immune response, biomarkers, and signs of treatment effect. Then, participants will be followed for an additional 42 months to continue safety and efficacy evaluations. Each participant's involvement lasts about five years, including up to 60 days for screening before treatment. Throughout the study, researchers will conduct medical assessments, laboratory tests, and biomarker analyses. They will closely monitor for any adverse events and immune reactions. The main goal is to track the occurrence and severity of any side effects that develop during the entire five-year period.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 with early symptoms of Alzheimer's disease, ranging from mild cognitive impairment to mild dementia. This Phase III clinical trial focuses on those who show evidence of Alzheimer's pathology and have a recent history of cognitive decline. The study aims to measure changes in cognitive function over 72 weeks. Participants will be randomly assigned to receive either intravenous trontinemab or a placebo. The trial is designed as a double-blind, placebo-controlled study, meaning neither participants nor researchers know who receives the active drug or placebo. The treatment period lasts up to 72 weeks, during which participants will undergo various assessments to monitor their cognitive status and safety. During the study, participants will complete clinical tests including cognitive assessments and imaging such as MRI, PET scans, or cerebrospinal fluid analysis to confirm Alzheimer's pathology. A study partner will assist participants as needed. Researchers will track changes from the start of the study through week 72 using tools like the Clinical Dementia Rating. Safety monitoring and adherence to study procedures will also be closely observed throughout the trial.

This research aims to learn about the safety and dosing of COM503, a drug being studied alone or combined with zimberelimab, in people with advanced solid tumors. It is a first-in-human Phase 1 clinical trial focused on participants with advanced or recurrent metastatic solid malignancies who have progressed despite standard treatments. The study seeks to assess safety, tolerability, and determine the best doses for future research. Participants will receive COM503 either alone or together with zimberelimab through intravenous infusions. The trial has two parts: dose escalation to find the maximum tolerated or administered dose, and dose expansion to further evaluate safety and dosing at identified levels. Both treatments are given as infusions, and the study monitors how well participants tolerate these therapies. During the study, participants will have their tumors measured by CT or MRI scans and will be closely monitored for safety from the first dose until 90 days after the last dose or start of a new cancer therapy. Researchers will evaluate side effects, tolerability, and other safety outcomes. Participation involves regular assessments and follow-up to understand the effects of COM503 alone or with zimberelimab in advanced cancer settings.