Plerin

Researchers are evaluating new treatments for advanced ovarian cancer in women who have completed initial surgery and chemotherapy. The study focuses on non-HRD positive ovarian cancer, comparing a targeted therapy called sacituzumab tirumotecan sac-TMT given alone or with bevacizumab, against standard care options such as bevacizumab maintenance or observation. The goal is to see if sac-TMT with or without bevacizumab can help patients live longer without their cancer worsening. Participants in the experimental group will receive sac-TMT through intravenous infusion on days 1, 15, and 29 of every 6-week cycle until the cancer progresses, side effects become prohibitive, or other reasons for stopping arise. They may optionally receive bevacizumab on days 1 and 22 of each cycle. The comparator group will either receive bevacizumab alone every 3 weeks for up to 22 courses or be monitored without active treatment. Supportive medications like steroid mouthwash and other rescue drugs are recommended before sac-TMT infusions. Throughout the study, participants will be regularly monitored for how long they live without their disease progressing, overall survival, side effects, and quality of life using specialized questionnaires. These assessments will continue for up to approximately 78 months. The study is randomized, with single masking, and led by Merck Sharp & Dohme LLC. Participants can expect regular visits for treatment and monitoring during this period.

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor CDK46i and letrozole compared to placebo plus CDK46i and letrozole in adults with endocrine-sensitive PIK3CA-mutated hormone receptor-positive HR, HER2-negative advanced breast cancer. This phase III, randomized, double-blind study focuses on participants who have measurable disease and meet specific hormone receptor and HER2 status criteria. Participants are randomly assigned to receive either oral inavolisib once daily along with letrozole and CDK46i or placebo once daily with letrozole and CDK46i. The CDK46i is given on a schedule of either Days 1-21 or Days 1-28 of each 28-day cycle. The study includes parallel groups to compare these treatment combinations over time. During the study, participants will be monitored for progression-free survival, overall survival, response rates, duration of response, clinical benefit, and changes in pain, physical function, and global health status. Safety will be assessed by tracking adverse events and patient-reported treatment side effects using questionnaires. The study will follow participants for up to seven years, with regular evaluations to track disease status and quality of life.

Researchers are evaluating the efficacy and safety of combining ficlatuzumab with cetuximab compared to cetuximab alone in people with recurrent or metastatic RM HPV-negative head and neck squamous cell carcinoma HNSCC. This Phase 3, randomized, double-blind, placebo-controlled study focuses on participants who have not responded to prior anti-PD-1PD-L1 immune checkpoint inhibitors and platinum-based chemotherapy. The goal is to see if adding ficlatuzumab improves survival outcomes in this patient group. Participants are assigned to one of three groups two groups receive different doses of intravenous ficlatuzumab plus cetuximab on days 1 and 15 of each 28-day cycle, while the third group receives a placebo plus cetuximab on the same schedule. The study will enroll about 410 participants and compare progression-free survival and overall survival among these groups. Treatment cycles continue until disease progression or other study endpoints. During the study, participants will undergo regular imaging scans CT or MRI to assess tumor response every 8 weeks during the first year, then every 12 weeks in years 2 and 3, and every 6 months thereafter. Researchers will monitor safety, quality of life, and immune responses, including antidrug antibodies. The study period spans approximately 44 months with ongoing evaluations from randomization until death or last response assessment.

Researchers are evaluating the effects of the drug imlunestrant LY3484356 in premenopausal women with early estrogen receptor-positive ER, HER2-negative breast cancer. The study includes two groups one that explores imlunestrant alone or combined with ovarian suppression, and another that studies imlunestrant without ovarian suppression. The trial compares imlunestrants impact on breast cancer cells and ovarian function to tamoxifen, a known treatment. Participants in Cohort 1 will receive imlunestrant orally either alone or with goserelin a drug given by injection to suppress ovarian function for up to 29 days. Some in this group will take tamoxifen orally as a comparator. Cohort 2 participants will take imlunestrant or tamoxifen orally for up to 6 months without ovarian suppression. The study is open-label, randomized, and phase 2, designed to assess treatment effects in parallel groups. During the study, participants will provide tumor samples before and during treatment, and researchers will monitor changes in specific cancer markers like Ki-67, estrogen receptor ER, and progesterone receptor PR expression. They will also track the rate of ovarian cysts up to 180 days. Participants must attend scheduled visits for evaluations, including performance status checks and safety assessments. The trial is expected to continue until December 2029.

Researchers are evaluating the safety and effectiveness of Raludotatug Deruxtecan R-DXd in adults with platinum-resistant, high-grade ovarian, primary peritoneal, or fallopian tube cancer. This study includes a Phase 2 dose-optimization part to find the best dose based on safety and effectiveness, followed by a Phase 3 part comparing R-DXd to chemotherapy chosen by the investigator. The study targets tumors that overexpress CDH6, a protein that R-DXd specifically binds to. Participants are randomly assigned to receive intravenous R-DXd at various doses every three weeks or an investigators choice of chemotherapy drugs including paclitaxel, pegylated liposomal doxorubicin, or topotecan. The Phase 2 portion focuses on determining the optimal dose, while the Phase 3 portion compares the recommended dose with standard chemotherapy. Treatments are given through IV infusions according to the assigned group. During the study, participants undergo scheduled visits for drug administration, safety monitoring, and evaluations including imaging scans to assess tumor response. Researchers measure outcomes such as objective response rate, progression-free survival, overall survival, duration of response, symptom changes, and pharmacokinetics over periods up to 40 months. Safety is closely monitored through adverse event tracking and laboratory tests, with participants followed until the studys completion in 2030.

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 zolbetuximab combined with pembrolizumab and chemotherapy in adults with stomach or gastroesophageal junction GEJ cancer. This study focuses on cancers that do not have the HER2 protein but do express Claudin 18.2. The goal is to understand how well zolbetuximab works with pembrolizumab and chemotherapy compared to a placebo with pembrolizumab and chemotherapy in people with advanced or metastatic disease that cannot be removed by surgery or has spread to other parts of the body. Participants will be randomly assigned to receive either zolbetuximab or a placebo, both given via intravenous infusion every 2 or 3 weeks, alongside pembrolizumab infusions every 3 or 6 weeks. Chemotherapy will be administered using one of two regimens, CAPOX or modified FOLFOX6, over multiple cycles lasting about 42 days each. Treatment continues until the cancer worsens, side effects prevent further use, or another therapy is needed. Pembrolizumab may be given for up to 2 years. During the study, participants will visit the clinic for infusions and health monitoring, including scans to check cancer status. Medical problems and treatment side effects will be recorded. After treatment ends, participants will continue to have regular health checks and scans every 9 to 12 weeks, along with phone check-ins every 3 months. The study will measure overall survival, disease progression, response rates, and safety over several years, with up to 72 months of follow-up for some outcomes.

This research aims to evaluate the safety and effectiveness of Mirvetuximab Soravtansine in female participants aged 18 years and older who have platinum-resistant advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high levels of folate receptor alpha FR. The study includes two groups a randomized Phase 2 group and a hepatic impairment group, with about 110 participants expected worldwide. The purpose is to better understand how this investigational antibody drug conjugate works by targeting cancer cells carrying FR to deliver a cell-killing drug. Participants in the randomized Phase 2 group receive Mirvetuximab Soravtansine intravenously on one of two schedules either a standard dose on day 1 every 21 days or a lower dose on days 1 and 15 every 28 days. The hepatic impairment group evaluates the starting dose for participants with moderately abnormal liver function, receiving different doses on day 1 of a 21-day cycle. Treatment and monitoring continue for up to about 24 months, including dose optimization and safety assessments. During the study, participants will visit the hospital or clinic regularly for medical exams, blood tests, and scans to track treatment effects and side effects. Researchers will measure responses including corneal adverse events, tumor response rates, drug concentrations in the body, and survival outcomes. Safety is closely monitored through assessments of vital signs, laboratory values, and physical exams. The total participation time is approximately 24 months, with ongoing evaluations to determine how well the treatment works and its safety profile.

Ovarian cancer is a serious disease with a high number of new cases and deaths worldwide. This study evaluates the safety and disease activity changes of mirvetuximab soravtansine combined with carboplatin, bevacizumab, or bevacizumab alone in female participants with ovarian cancer confirmed to express folate receptor alpha FR. The trial is a Phase 2 study involving approximately 400 participants worldwide, assessing different treatment combinations given by intravenous infusion. Participants will be assigned to one of three substudies and receive treatment in groups called arms. Substudy 1 includes arms where participants receive one of two doses of mirvetuximab soravtansine with bevacizumab or bevacizumab alone. Substudy 2 involves mirvetuximab soravtansine with carboplatin followed by mirvetuximab soravtansine alone. Substudy 3 combines mirvetuximab soravtansine, bevacizumab, and carboplatin followed by mirvetuximab soravtansine with bevacizumab. Treatments are given by intravenous infusion, and the study duration ranges up to approximately 40 months depending on the substudy. Participants will attend regular visits at hospitals or clinics where they will receive infusions and undergo medical assessments including blood tests and scans. Researchers will monitor treatment-emergent adverse events, ocular events, overall response, progression-free survival, and other outcomes up to about 40 months. The study includes careful safety monitoring and evaluation of disease activity during and after treatment to assess the effects and safety of these drug combinations.

Researchers are investigating new treatments for people with proficient mismatch repair pMMR endometrial cancer that is advanced or has returned after surgery. This cancer starts in the tissues inside the uterus and has spread locally or to other parts of the body, making it not removable by surgery. The study aims to learn if combining sacituzumab tirumotecan sac-TMT with pembrolizumab helps people live longer and without their cancer worsening compared to pembrolizumab alone. All participants first receive an Induction Phase of six cycles, each lasting three weeks, which includes pembrolizumab combined with carboplatin or cisplatin and paclitaxel or docetaxel. Those whose cancer does not progress then enter a Maintenance Treatment Phase and are randomly assigned to receive either pembrolizumab plus sac-TMT or pembrolizumab alone. If the cancer progresses, participants may enter a Subsequent Treatment Phase where they are randomly assigned to pembrolizumab plus sac-TMT or sac-TMT alone. During maintenance and subsequent phases, sac-TMT is given on Days 1, 15, and 29 of each 6-week cycle, and pembrolizumab is given on Day 1 of each 6-week cycle. Participants are involved throughout the study, receiving intravenous treatments over several months and up to 14 maintenance cycles lasting about 19 months. Researchers will monitor cancer progression and survival up to approximately 44 to 54 months. They also assess safety by tracking adverse events and quality of life using questionnaires. The study requires regular visits for treatment and evaluation over this period to understand how well the treatments work and their effects on participants.