Pamplona

Researchers are evaluating the safety, tolerability, and therapeutic effects of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first-line treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC positive for human papilloma virus 16 HPV16 and expressing the protein PD-L1 with a combined positive score of 1 or higher. This is an open-label, multi-site, Phase IIIII clinical trial consisting of two parts an initial safety run-in phase and a randomized phase. In the safety run-in phase Part A, patients receive BNT113 in combination with pembrolizumab to confirm safety and tolerability at selected dose levels. The randomized phase Part B compares BNT113 combined with pembrolizumab against pembrolizumab monotherapy. Treatments are given by intravenous injection or infusion and continue for up to 24 months. An optional pre-screening phase allows tumor samples to be tested for HPV16 DNA and PD-L1 expression before the main trial screening. Participants will be closely monitored throughout the study. Assessments include safety evaluations, tumor response, and survival outcomes such as overall survival and progression-free survival. Tumor tissue samples must be provided for testing. Researchers will measure treatment-emergent adverse events, response rates, duration of response, and disease control. The study may last up to 48 months, with ongoing safety and efficacy monitoring during and after treatment.

Researchers are studying the safety and effects of VHB937 in people with early Alzheimers disease, including those with Mild Cognitive Impairment due to Alzheimers or mild Alzheimers itself. This randomized, double-blind, placebo-controlled Phase II trial aims to evaluate whether VHB937 can benefit memory, thinking abilities, daily functioning, and brain changes. The study also looks at how the body processes VHB937 and responds to it. Participants receive intravenous infusions of either a low dose or high dose of VHB937, or a placebo, over a 72-week double-blind period. After this, an extension phase follows for further observation. The treatments are given through infusions, and participants are randomly assigned to one of the three groups in parallel. Throughout the study, participants and their study partners attend regular visits for assessments including clinical dementia rating scales, cognitive tests, daily living activities evaluation, and brain imaging biomarkers. Safety is monitored by tracking adverse events and serious adverse events. Blood samples are collected to measure VHB937 levels and immune responses. The total study duration includes the 72-week treatment period plus additional time in the extension phase.

Researchers are investigating a combination therapy of BNT326 and pumitamig also called BNT327 or PM8002 in adults with advanced or metastatic non-small cell lung cancer NSCLC who may have relapsed, progressive, or treatment-nafve disease. This multi-site, open-label study aims to find the best dose levels for this combination, assess how well participants tolerate the therapy, including side effects, and evaluate its ability to shrink tumors in this population. The study has three parts Part 1 focuses on finding safe dose levels for the combination Part 2a expands the dose evaluation to assess preliminary effectiveness and safety Part 2b is a randomized phase to optimize doses and understand the contribution of each drug component. Participants will receive intravenous infusions of BNT326 and pumitamig or pumitamig alone in some arms. Treatment continues until disease progression, unacceptable side effects, withdrawal, study end, or up to 24 months. Dose levels for later parts are chosen based on earlier safety and efficacy data. Participants will go through screening, treatment, safety follow-up, efficacy follow-up, and long-term survival follow-up phases, with total involvement expected to last about 36 months unless treatment benefit continues. Assessments include monitoring for dose-limiting toxicities, adverse events, tumor response, progression-free survival, overall survival, and pharmacokinetics of the drugs. Safety evaluations continue up to 90 days after treatment ends, and antibody responses to the drugs are also measured for up to one year post-treatment.

Researchers are evaluating CPV-104, a new medicine designed to regulate the complement system, which can be overactive in diseases such as C3 glomerulopathy C3G, a very rare kidney disorder. This phase 1 trial is the first time CPV-104 is being tested in people, including both healthy adults and adults with C3G, to assess its safety, tolerability, how the body processes the medicine, and whether the immune system reacts to it. The study has two parts Part 1 involves healthy volunteers receiving a single intravenous dose of CPV-104 or a placebo in a randomized, double-blind manner across several dose levels. Part 2 includes patients with C3G receiving four weekly intravenous doses of CPV-104 without placebo. Doses are escalated if the medicine is tolerated, and a Safety Review Committee regularly reviews results to ensure safety before progressing. Participants will undergo close monitoring throughout the study, including side-effect checks, blood and urine tests, ECGs, vital signs, and blood samples to measure drug levels and antibodies. For C3G patients, kidney function will also be observed. The primary outcome is the incidence of severe and serious adverse drug reactions up to Day 29 for healthy volunteers and Day 50 for C3G patients. The total study duration varies by part, with detailed safety assessments conducted throughout.

Researchers are evaluating zorevunersen, an investigational antisense oligonucleotide drug, in children with Dravet syndrome, a rare and severe form of epilepsy. This Phase 3, global, multicenter, randomized, double-blind, sham-controlled study aims to assess the efficacy, safety, and tolerability of zorevunersen by measuring changes in major motor seizure frequency and other important aspects such as behavior, cognition, clinical status, and quality of life. Participants will be randomly assigned to receive either zorevunersen or a sham procedure during Treatment Period 1, which lasts about 52 weeks. Zorevunersen is given by intrathecal injection at specific doses and intervals throughout this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen for additional dosing over several months. Patients who complete the study may have the chance to join an open-label extension to continue receiving the drug. During the study, participants will undergo regular assessments including seizure monitoring, behavioral and cognitive evaluations, and health-related quality of life measurements. The primary outcome is the change in major motor seizure frequency at Week 28, with secondary outcomes assessed at Week 52. Safety and tolerability are also closely monitored. Overall participation lasts through both treatment periods and possible extension, with detailed follow-up to evaluate the drugs potential for disease modification.

Researchers are establishing a European registry and sample sharing network called EUREKA to collect new cases of AL amyloidosis from referral centers and their satellite sites across Europe. This observational study aims to use advanced molecular technologies and big data analysis, including artificial intelligence, to better understand the disease mechanisms, improve early diagnosis, and guide treatment decisions. The study also seeks to describe the natural history of AL amyloidosis in patients receiving modern anti-plasma cell therapies and to refine methods for detecting minimal residual disease after treatment. The study involves creating a biorepository and sample sharing network to study disease-causing light chains and plasma cells using cutting-edge molecular techniques. A dedicated site will support the consortium with big data and AI applied to health data. Participants will be followed over time at participating centers, with data collected to assess outcomes such as mortality and hematologic relapse in those achieving complete response to therapy. Participants will be involved through regular follow-up visits at their treatment centers, with collection of clinical data and biological samples. Researchers will monitor outcomes including mortality at 24 months after diagnosis and rates of relapse in patients with minimal residual disease. The study duration allows for long-term observation to better understand disease progression and response to treatment in a real-world setting.

Researchers are evaluating VVD-130037, a Kelch-like ECH Associated Protein 1 KEAP1 activator, in adults with advanced solid tumors in a first-in-human study. The study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of VVD-130037, both alone and combined with other cancer treatments. This is an open-label, phase 1 trial sponsored by Vividion Therapeutics, Inc., focusing on patients whose cancer has progressed despite prior standard therapies. Participants receive escalating doses of VVD-130037 orally once or twice daily in 21- or 28-day treatment cycles. In Part 1 dose escalation, VVD-130037 is tested alone and combined with intravenous docetaxel, paclitaxel, or pembrolizumab at established schedules. Part 2 dose expansion administers VVD-130037 at the recommended dose for expansion RDE, alone or in combination, to further evaluate safety and activity. Treatment cycles vary by combination, with docetaxel given every 3 weeks and paclitaxel given on days 1, 8, and 15 of each cycle. Participants undergo regular assessments including monitoring for dose-limiting toxicities during the first treatment cycle and tracking adverse events over up to 4 years. Laboratory tests, electrocardiograms, and imaging evaluations measure drug concentrations, heart rhythm, and tumor response. Researchers also evaluate overall response rates, duration of response, progression-free survival, and disease control rates. Safety follow-up and detailed pharmacokinetic studies are part of the long-term observation to understand the effects of VVD-130037 and its combinations.

Researchers are evaluating AZD8421 alone and in combination with targeted anti-cancer drugs in patients with ER HER2- advanced breast cancer and metastatic high-grade serous ovarian cancer. This first-in-human study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AZD8421, both as a single treatment and combined with other therapies, in participants previously treated for these cancers. The study includes two main treatment modules AZD8421 monotherapy to determine a recommended dose in patients with specific advanced breast and ovarian cancers, and AZD8421 combined with camizestrant and CDK46 inhibitors in advanced breast cancer patients. Participants receive these treatments in cycles, with safety and response monitored closely. The study uses a sequential model to evaluate these approaches. Participants will undergo various assessments including clinical lab tests, vital signs, ECGs, and tumor measurements to monitor treatment effects and safety throughout the study, which includes an approximately 18-month safety follow-up. Researchers will track dose-limiting toxicities, adverse events, response rates, tumor changes, and pharmacokinetic profiles during treatment and follow-up periods.

Researchers are studying MEN2501, an oral drug, in adults with platinum-resistant ovarian cancer including high-grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. This first-in-human, open-label trial aims to assess the safety, tolerability, how the drug moves through the body, its effects, and antitumor activity. The study is conducted in two parts dose escalation and dose expansionoptimization. In Part A, participants receive increasing doses of MEN2501 to evaluate dose-limiting toxicities during the first 28-day cycle. Part B focuses on determining the recommended phase 2 dose over approximately six months. The drug is given orally as tablets. The trial uses a sequential study model with randomized allocation and no masking. Participants will be monitored for treatment-emergent adverse events, tumor response rates, duration of response, clinical benefit, progression-free survival, overall survival, and drug concentration levels. These assessments occur over periods ranging from about six to twelve months. The total study duration extends to June 2028, with ongoing safety and efficacy follow-up through primary and secondary outcome measures.

Researchers are evaluating the safety, tolerability, and preliminary effectiveness of IMP1734, a PARP1 selective inhibitor, in people with advanced solid tumors. This study includes patients with breast cancer, metastatic prostate cancer, ovarian cancer, and other solid tumors who have previously received certain treatments. The goal is to find an optimal dose for future clinical development by studying how the drug affects the body and how the body processes it. The study has two parts Part 1 involves gradually increasing doses of IMP1734 given as a daily oral tablet to identify the highest safe dose or maximum achievable dose. This includes testing the drug alone and in combination with other treatments for specific cancers like metastatic prostate, ovarian, and breast cancer. Part 2 focuses on refining the dose to find the best amount for future studies. Treatment can last up to three years after the first dose. Participants will be monitored closely with assessments of side effects, blood tests to study drug levels and effects, and evaluations of tumor response using standard criteria. Safety monitoring continues up to 30 days after the last dose. Researchers measure how well the drug is tolerated and its impact on the cancer over time. The total participation may extend up to three years, with ongoing evaluations during this period.