Saarbrucken

Researchers are investigating new treatments for high-risk, early-stage breast cancers that are either triple-negative or hormone receptor-low positive and HER2-negative. These types of breast cancer have limited amounts of certain proteins that affect growth, making them challenging to treat. This Phase 3 trial aims to compare the effects of adding sacituzumab tirumotecan, a targeted therapy, to pembrolizumab and chemotherapy against pembrolizumab with chemotherapy alone in controlling cancer growth and spread. Participants are randomly assigned to one of two treatment groups. One group receives sacituzumab tirumotecan intravenously every two weeks along with pembrolizumab every three weeks for 12 weeks, followed by pembrolizumab combined with carboplatin and paclitaxel for another 12 weeks. After this, surgery and optional radiation therapy occur, followed by pembrolizumab infusions for up to about 28 weeks. Additional treatments such as olaparib, capecitabine, or doxorubicin with cyclophosphamide may be given if cancer remains. The other group receives chemotherapy drugs carboplatin, paclitaxel, cyclophosphamide, and doxorubicin or epirubicin alongside pembrolizumab during similar time frames, followed by surgery, radiation, and pembrolizumab maintenance with possible additional treatments. Throughout the study, participants undergo assessments including surgery to remove tumors, imaging, and laboratory tests. Researchers measure cancer cell presence after surgery and monitor how long participants live without cancer progression or recurrence, as well as overall survival. Quality of life and side effects are tracked using questionnaires over several years. Safety is monitored by recording adverse events and treatment discontinuations. The study may last up to around 115 months for long-term follow-up.

Researchers are evaluating the safety, tolerability, and effectiveness of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC that tests positive for human papillomavirus 16 HPV16 and expresses the protein PD-L1. This Phase IIIII trial includes patients whose tumors have a combined positive score of 1 or higher for PD-L1. The study is designed to generate important safety and efficacy data for these treatments in this patient group. The trial consists of two parts Part A is a non-randomized safety run-in phase to confirm the safety and tolerability of BNT113 with pembrolizumab. Part B is a randomized phase comparing BNT113 combined with pembrolizumab versus pembrolizumab alone. Treatments are given by intravenous injection or infusion. Patients may receive treatment for up to 24 months. An optional pre-screening phase allows tumor samples to be tested centrally for HPV16 DNA and PD-L1 expression before entering the main trial. Participants will undergo regular assessments including monitoring for treatment-emergent adverse events, overall survival, and progression-free survival for up to 48 months. Researchers will also measure response rates and duration, disease control, and any dose adjustments due to side effects. Patients provide tumor tissue samples before treatment and are monitored closely throughout the study period. The trial aims to collect comprehensive data on safety, treatment effects, and patient outcomes over this extended follow-up.

Researchers are evaluating treatments for patients with high-risk chronic lymphocytic leukemia CLL, a type of blood cancer that is aggressive and currently incurable. This phase 3, open-label, multicenter, randomized study aims to compare the effectiveness of a triple drug combination acalabrutinib, obinutuzumab, and venetoclax against a double combination obinutuzumab and venetoclax in prolonging progression-free survival PFS for patients with specific high-risk genetic features such as 17p-deletion, TP53 mutation, complex karyotype, or unmutated IGHV gene status. The study addresses a crucial medical need for better treatments in this difficult-to-treat group. Participants will be randomly assigned to one of two treatment groups. One group receives the triple combination of acalabrutinib, obinutuzumab, and venetoclax, while the other group receives obinutuzumab plus venetoclax. Obinutuzumab is given as intravenous infusions on specific days across six cycles. Venetoclax is taken orally with a carefully planned dose escalation and maintenance over 12 cycles. Acalabrutinib is administered orally twice daily during cycles 15 to 24. The study explores whether adding acalabrutinib improves outcomes by using these fixed-duration, chemotherapy-free regimens. Throughout the study, participants will undergo regular assessments to monitor response and safety, including checks for minimal residual disease MRD and overall survival. These evaluations occur up to 50 months after the first patient is enrolled. Researchers will also track progression-free survival, complete and overall response rates, event-free survival, duration of response, and time to next treatment. Safety monitoring and laboratory tests will be performed as part of study visits. The total study participation is expected to last several years to capture long-term outcomes for this high-risk patient population.

Researchers are evaluating the effectiveness and safety of combining inavolisib with a CDK46 inhibitor and letrozole compared to a placebo combined with a CDK46 inhibitor and letrozole. This study focuses on participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive, HER2-negative advanced breast cancer. The trial is a Phase III, multicenter, randomized, double-blind, placebo-controlled study sponsored by Hoffmann-La Roche. Participants are assigned to one of two groups one receiving oral inavolisib daily along with letrozole and a CDK46 inhibitor, and the other receiving a placebo with letrozole and a CDK46 inhibitor. The CDK46 inhibitor is given either on Days 1-21 or Days 1-28 of each 28-day cycle. Treatment will continue as per the study protocol while monitoring responses and safety. During the trial, participants will have measurable disease evaluated regularly using RECIST v1.1 criteria. Researchers will monitor progression-free survival from randomization up to seven years, alongside other outcomes such as overall survival, response rates, duration of response, and quality of life measures including pain and physical function. Safety will be assessed through adverse event tracking and patient-reported outcomes throughout the follow-up period.

Researchers are evaluating treatments for people with hormone receptor positivehuman epidermal growth factor receptor-2 negative HRHER2- breast cancer that cannot be removed by surgery or has spread to other parts of the body. This study compares sacituzumab tirumotecan alone and in combination with pembrolizumab to the Treatment of Physicians Choice TPC. The goal is to see which approach better controls disease progression based on specific tumor response criteria. Participants are assigned to one of three groups one group receives sacituzumab tirumotecan intravenously every two weeks, another group receives the same drug plus pembrolizumab intravenously every six weeks for up to about two years, and the third group receives chemotherapy chosen by the doctor, which may include various drugs administered either by infusion or orally. Treatments continue until the disease worsens or participants stop treatment. During the study, participants undergo regular assessments to monitor how well treatments control cancer progression, overall survival, and response to therapy. Quality of life and physical and emotional functioning are also measured using specific questionnaires. Safety is closely watched by tracking any side effects or reasons for stopping treatment. The study lasts up to several years, with some outcomes followed for up to about six years after starting treatment.

Researchers are investigating sacituzumab tirumotecan alone or combined with pembrolizumab to treat triple negative breast cancer TNBC that is locally recurrent, unresectable, or metastatic and expresses PD-L1 at a combined positive score less than 10. The study aims to determine if these treatments help people live longer overall or without their cancer growing or spreading compared to chemotherapy selected by their physician. This is a phase 3, randomized, open-label study sponsored by Merck Sharp Dohme LLC. Participants are randomly assigned to one of three groups sacituzumab tirumotecan given intravenously every two weeks sacituzumab tirumotecan every two weeks plus pembrolizumab every six weeks for up to about two years or chemotherapy chosen by the physician, which includes options like paclitaxel, nab-paclitaxel, gemcitabine plus carboplatin with various dosing schedules. Pre-medications are given before sacituzumab tirumotecan infusions to help manage side effects. Treatments continue until disease progression, unacceptable side effects, or discontinuation. During the study, participants will be monitored for overall survival and progression-free survival up to about 61 months. Researchers will assess tumor response, duration of response, quality of life using questionnaires, and safety including adverse events and treatment discontinuations. The study includes regular visits for treatment administration, assessments, and follow-up to evaluate how participants respond and tolerate the treatments over time.

Researchers are evaluating trastuzumab deruxtecan T-DXd as a treatment for adult patients with advanced HER2-positive gastric or gastroesophageal junction GEJ adenocarcinoma who have previously received a trastuzumab-based regimen. This study aims to assess the real-world effectiveness of T-DXd, patient characteristics, treatment patterns, and safety in this population. It also includes data collection on patients receiving conventional therapies for exploratory comparison. This is a non-interventional observational study where patients receive T-DXd or conventional therapies as part of routine clinical care according to approved guidelines SmPC. No investigational drugs are given. The study tracks patients starting T-DXd as a second-line or later treatment and collects data on other therapies such as chemotherapy and immunotherapy used in clinical practice. Participants will be followed for up to approximately 2 years from baseline to monitor outcomes including time to next treatment, changes in treatment, physician-reported safety events, use of prophylactic treatments, and quality of life using validated questionnaires. Data on physician visits, treatment discontinuation, and safety events will also be collected to understand treatment tolerability and patient experience in a real-world setting.

Researchers are evaluating zolbetuximab combined with pembrolizumab and chemotherapy for adults with stomach or gastroesophageal junction GEJ cancer that is locally advanced, unresectable, or metastatic. This study focuses on cancers that do not have the HER2 protein but do express Claudin 18.2 and PD-L1 proteins. The goal is to find out how long people live after receiving zolbetuximab with pembrolizumab and chemotherapy compared to a placebo with the same treatments. Participants will receive treatment in 6-week cycles. The study treatment includes zolbetuximab or a placebo given by infusion every 2 or 3 weeks, combined with pembrolizumab infusions every 3 or 6 weeks. Chemotherapy options include CAPOX capecitabine tablets twice daily and oxaliplatin infusion or mFOLFOX6 infusions of oxaliplatin, folinic acid, and 5-fluorouracil. After several cycles, participants may receive parts of the chemotherapy alone. Treatment continues until the cancer worsens, side effects prevent continuation, or another cancer treatment is needed. Pembrolizumab may be given for up to 2 years. During the study, participants will visit the clinic for treatment and health checks, including scans to monitor cancer changes. Researchers will watch for medical problems related to zolbetuximab and other treatments. Tumor samples may be collected if treatment stops because of cancer progression. After stopping treatment, participants will have continued health checks and scans every 9 to 12 weeks, plus telephone check-ins every 3 months. The frequency of visits depends on each persons health and treatment status.

Researchers are studying new treatment options for people with proficient mismatch repair pMMR endometrial cancer that is either advanced or has returned after surgery. This type of cancer starts in the lining of the uterus and pMMR means the cancer cells have certain normal proteins. The study aims to see if combining sacituzumab tirumotecan sac-TMT with pembrolizumab helps people live longer without their cancer worsening compared to pembrolizumab alone. Participants begin with an Induction Phase where they receive pembrolizumab along with carboplatin and either paclitaxel or docetaxel every three weeks for six cycles about 4 months. After this, if the cancer does not progress, participants enter the Maintenance Treatment Phase and are randomly assigned to receive pembrolizumab plus sac-TMT or pembrolizumab alone every six weeks for up to 14 cycles about 19 months. Those whose cancer progresses may enter a Subsequent Treatment Phase and receive either pembrolizumab plus sac-TMT or sac-TMT alone on a similar schedule. Throughout the study, participants will have regular assessments including scans to measure cancer progression, evaluations of overall health, and questionnaires about quality of life. Researchers will track how long participants live without cancer worsening and overall survival for up to approximately 44 to 54 months. Safety and side effects will also be monitored closely during the treatment phases. Total participation may last several years depending on individual treatment and response.

Researchers are evaluating the safety and effectiveness of inavolisib combined with Phesgo compared to a placebo combined with Phesgo as maintenance treatment in people with untreated HER2-positive advanced breast cancer that has a specific PIK3CA mutation. This study is a Phase III, randomized, double-blind trial designed to assess this combination after initial induction therapy. Participants will first receive induction therapy with Phesgo and taxane-based chemotherapy. After this, they will be randomly assigned to receive either inavolisib tablets daily plus Phesgo administered subcutaneously every three weeks, or a matching placebo tablet plus Phesgo on the same schedule. Optional endocrine therapies may be given based on the investigators choice. Treatment cycles last 21 days, and the study includes long-term follow-up. During the trial, participants will undergo regular assessments including scans, laboratory tests, and quality of life questionnaires. Researchers will monitor progression-free survival for up to approximately 40 months and overall survival and other response measures for up to 111 months. Safety will be closely observed throughout treatment and for 30 days after the last dose. Plasma levels of inavolisib will be checked at specific times, and participants will be followed periodically for survival and health status.