Donostia San Sebastian

Researchers are evaluating the effectiveness and safety of an investigational drug called BNT323 also known as DB-1303 compared with standard chemotherapy in women with recurrent endometrial cancer. The study includes two groups based on the level of HER2 protein in the tumor Cohort 1 with HER2 levels 1 or 2 who have been previously treated with immune checkpoint inhibitors, and Cohort 2 with HER2 level 3. The study aims to understand how well BNT323 or chemotherapy controls cancer progression and how the drug affects patients immune response and quality of life. Participants in Cohort 1 will be randomly assigned to receive either BNT323 or chemotherapy drugs such as doxorubicin, paclitaxel, or docetaxel. In Cohort 2, participants will receive BNT323 alone. Treatments are given intravenously and continue until the cancer progresses, unacceptable side effects occur, or consent is withdrawn. The study includes screening, treatment, safety follow-up, efficacy follow-up, and a long-term survival follow-up lasting up to about 53 months. During the study, participants will undergo regular assessments including tumor evaluations, safety monitoring, and quality of life questionnaires. Researchers will measure progression-free survival in Cohort 1 and tumor response rate in Cohort 2. Safety is monitored by tracking adverse effects and drug levels in the body. Participants can expect to be followed for up to 53 months after treatment to assess long-term outcomes and survival.

Researchers are evaluating the effectiveness, safety, and tolerability of camizestrant combined with ribociclib in patients with advanced ER-positive, HER2-negative breast cancer who have not received any prior systemic treatment for their advanced disease. This Phase IIIb global, multicenter, single-arm study aims to provide insight into this combination therapy as a first-line treatment option. Participants will receive daily oral tablets of camizestrant 75 mg and ribociclib 600 mg at standard doses continuously until they choose to stop treatment or it is discontinued for any reason. Approximately 150 participants will be enrolled and treated within this trial. During the study, participants will be monitored for treatment effectiveness using time to next treatment, time to discontinuation, and progression-free survival over a two-year period. Safety will be assessed by tracking adverse events, including any severe toxicities within the first six months. Participants will undergo regular assessments related to organ function and performance status throughout the treatment period, which may last until discontinuation.

This research aims to observe the real-world use and effects of pegcetacoplan in adults diagnosed with Paroxysmal Nocturnal Hemoglobinuria PNH. As a new treatment with a unique mechanism of action, pegcetacoplans effectiveness and safety in routine medical practice are being studied to provide valuable information for patients, healthcare providers, and payers. The study will also gather data on blood transfusions and healthcare resource use before and after starting pegcetacoplan. Patients who have started pegcetacoplan treatment within the past 12 months or are prescribed the drug at enrollment will be included. Data collection includes retrospective information from up to 12 months before treatment start and prospective monitoring for approximately 36 months, with the total data period extending up to about 48 months. After stopping pegcetacoplan, patients remain in the study for 8 weeks to record any adverse events. Patients continue regular clinic visits, where data from each visit will be gathered. Participants will have data collected on various health measures such as hemoglobin levels, blood markers, transfusion needs, and patient and physician treatment satisfaction at regular intervals up to 36 months. Safety and adverse events will be monitored throughout. The main outcome measured is the change in hemoglobin level from treatment start to 6 months. This long-term observational study allows for comprehensive tracking of pegcetacoplans use and effects over time in usual care settings.

Researchers are evaluating targeted therapies and immunotherapy for people with metastatic colorectal cancer mCRC that have specific biomarkers. This open-label, exploratory Phase 11b study aims to assess the safety and effectiveness of these treatments alone or in combination. Eligible participants will be assigned to treatment arms based on their tumor biomarker test results to better understand how these therapies work in different subgroups of mCRC. Participants may receive various drug combinations including oral inavolisib, intravenous IV cetuximab, bevacizumab, atezolizumab, tiragolumab, SY-5609, divarasib, and chemotherapy regimens such as FOLFOX or FOLFIRI. Treatment cycles typically last 21 or 28 days, with dosing schedules varying across arms, including daily oral medications and IV infusions on specific days. Some arms are actively recruiting, while others are closed or not currently enrolling. During the study, participants will undergo regular assessments including tumor measurements to evaluate response, blood tests to monitor drug levels and safety, and collection of tumor tissue for biomarker research. The primary outcome is the objective response rate over about 7 years. Secondary outcomes include duration of response, disease control rate, and adverse event monitoring. Participants are followed long-term to assess treatment effects and safety, with study participation lasting up to approximately 84 months.

The trial investigates the safety and effectiveness of a combination of two investigational kinase inhibitor drugs, avutometinib and defactinib, compared to standard treatments chosen by doctors for women with recurrent low-grade serous ovarian cancer LGSOC who have not responded to prior platinum-based therapy. The goal is to improve progression-free survival and evaluate overall survival, safety, quality of life, and disease symptoms in this patient group. Participants will receive either the combination of avutometinib taken orally twice weekly and defactinib taken orally twice daily on a 21 days on, 7 days off schedule per 28-day cycle, or one of four standard treatments selected by their doctor. These standard treatments include intravenous pegylated liposomal doxorubicin, intravenous paclitaxel, or oral anastrozole or letrozole, each given according to specified doses and schedules. Patients initially receiving standard treatments who experience disease progression may switch to the investigational combination. During the study, participants will have regular follow-up visits to monitor their health, side effects, and disease progression over up to 24 months for progression-free survival and up to 5 years for overall survival. Researchers will assess tumor response, adverse events, drug levels in blood, and quality of life using validated questionnaires. The study involves randomized assignment to treatment groups and includes ongoing assessments to understand the impact of therapies on cancer control and patient well-being.

This trial is a Phase 2 study evaluating axatilimab, an antibody targeting the colony stimulating factor 1 receptor, in participants aged 2 years and older with recurrent or refractory active chronic graft versus host disease cGVHD. These participants have previously received at least two lines of systemic therapy but still have active disease requiring further treatment. The study aims to assess the efficacy, safety, and tolerability of axatilimab at different dose levels in this population. Participants will be randomly assigned to one of three axatilimab dosing regimens administered intravenously. The doses include 0.3 mgkg every two weeks, 1 mgkg every two weeks, or 3 mgkg every four weeks. Treatment cycles last 28 days and may continue for up to two years. This open-label, multicenter study allows participants to receive axatilimab while being closely monitored. During the study, participants will have regular assessments to evaluate treatment response based on established NIH criteria for cGVHD. Researchers will measure overall response rates in the first six cycles as well as throughout the study period of up to two years. Other evaluations include symptom scales, organ-specific responses, medication use changes, laboratory biomarkers, and safety monitoring. Participants are followed for efficacy, tolerability, and adverse events during treatment and for the full study duration.

Researchers are studying the use of bempedoic acid combined with ezetimibe and either rosuvastatin or atorvastatin, known as triple therapy, in adults with primary hypercholesterolemia or mixed dyslipidemia. The study aims to evaluate the effectiveness and safety of this combination in real-world clinical practice, focusing on lowering LDL cholesterol LDL-C levels. This is an observational study, meaning no drugs are administered by the study team instead, existing treatments are monitored. Participants are adults who have started triple therapy within the past four weeks and are followed for up to one year. The study looks at LDL-C changes after 8 weeks and 1 year of treatment, adherence to the therapy, side effects, and cardiovascular events such as heart attacks and strokes. No new treatments are given instead, researchers collect information on the participants ongoing treatments involving bempedoic acid, ezetimibe, and either rosuvastatin or atorvastatin. During the study, participants LDL-C levels, laboratory values, and treatment adherence are regularly reviewed. Researchers will also record any adverse events and track major cardiovascular events over the year. The primary measurement is the change in LDL-C from before treatment to 8 weeks after starting triple therapy. Participants health is followed through routine clinical assessments, and the study lasts for up to one year after beginning triple therapy.

Researchers are studying the safety, tolerability, and effectiveness of Debio 0123 combined with temozolomide TMZ, with or without radiotherapy RT, in adults with glioblastoma GBM and grade III astrocytoma. This Phase 12 trial aims to find dose-limiting toxicities and the recommended dose for Debio 0123 in combination with TMZ. The study also compares this combination to the standard of care in participants with recurrent, progressive, or newly diagnosed glioblastoma. Participants receive intermittent escalating doses of Debio 0123 capsules along with TMZ capsules in 28-day cycles for up to two years. In some study arms, radiotherapy is given concurrently for about six weeks. Phase 1 includes dose escalation and dose expansion to determine the best dose. Phase 2 tests the recommended doses efficacy compared to standard treatment. One arm involving Debio 0123 with TMZ and radiotherapy has been permanently halted due to safety concerns. During the study, participants undergo regular assessments including brain MRI scans to measure tumor response using RANO criteria, blood tests, vital sign monitoring, electrocardiograms, echocardiograms, and performance status evaluations. Researchers monitor adverse events, pharmacokinetics of Debio 0123 and TMZ, and overall survival. The study may last up to approximately 66 months, with safety follow-up continuing for 30 days after treatment ends.

Researchers are evaluating the efficacy and safety of iza-bren, a bi-specific antibody-drug conjugate targeting EGFR and HER3 with a chemotherapy payload, compared to treatment chosen by physicians including paclitaxel, nab-paclitaxel, carboplatin plus gemcitabine, and capecitabine for patients with first-line metastatic triple-negative breast cancer TNBC or low estrogen receptor ER-low, HER2-negative breast cancer who cannot receive anti-PDL1 or endocrine therapies. This study includes adults with locally advanced, recurrent inoperable, or metastatic disease who meet specific eligibility criteria. Participants are randomly assigned to receive iza-bren or one of the physicians choice chemotherapy regimens. The treatments are given at specified doses on scheduled days. The study includes two phases Phase 2 to determine the recommended dose of iza-bren and Phase 3 to compare progression-free survival and other outcomes. The study will last several years, with follow-up extending up to approximately 47 months after randomization. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests, and monitoring for adverse events. Quality of life questionnaires will also be completed. Researchers will track progression-free survival, overall survival, treatment-related side effects, tumor size changes, and patient-reported outcomes to evaluate the treatments. The total participation duration may extend up to several years depending on treatment response and follow-up requirements.

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.