Plerin

Researchers are evaluating the effectiveness and safety of combining inavolisib with a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole compared to placebo plus CDK4/6i and letrozole. This study focuses on participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. It aims to assess treatment outcomes in the first-line setting for this specific breast cancer type. Participants will be assigned to receive either oral inavolisib once daily or a matching oral placebo once daily. All participants will also receive a CDK4/6 inhibitor on either Days 1-21 or Days 1-28 of each 28-day cycle, along with daily oral letrozole. This randomized, double-blind study will compare these two treatment combinations to monitor differences in disease progression and safety. Throughout the study, researchers will evaluate progression-free survival from the time of randomization until disease progression or death, up to 7 years. Participants will undergo assessments including tumor measurements by RECIST criteria, performance status evaluations, and monitoring of blood and organ function before treatment begins. Safety and efficacy will be closely observed during treatment, aiming to provide detailed long-term data on the study therapies.

Researchers are evaluating the effectiveness and safety of combining ficlatuzumab with cetuximab compared to cetuximab alone in adults with recurrent or metastatic human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). This phase 3 study focuses on participants whose cancer has returned or spread and who have previously been treated with anti-PD-1/PD-L1 immune checkpoint inhibitors and platinum-based chemotherapy. The main goal is to see if the combination improves progression-free survival and overall survival. Participants will be randomly assigned to one of three groups: two groups will receive different doses of ficlatuzumab plus cetuximab, and the third group will receive a placebo plus cetuximab. Treatments involve infusions of biological agents, with ficlatuzumab being a monoclonal antibody targeting hepatocyte growth factor (HGF) and cetuximab being an epidermal growth factor receptor (EGFR) antagonist. The study will enroll about 410 participants and is double-blinded, meaning neither participants nor researchers know who is receiving ficlatuzumab or placebo. During the study, participants will be monitored regularly through imaging scans (CT or MRI) to measure tumor response, along with physical exams and laboratory tests. Researchers will track overall survival from the time of randomization until death from any cause, which may take approximately 44 months. Safety assessments and compliance with study procedures will also be closely observed throughout the trial.

Researchers are evaluating the safety and effectiveness of Raludotatug Deruxtecan (R-DXd) in people with platinum-resistant, high-grade ovarian, primary peritoneal, or fallopian tube cancer. This study includes two parts: Phase 2 to find the best dose based on safety and response, and Phase 3 to compare R-DXd with the investigator's choice of chemotherapy. R-DXd is an antibody-drug conjugate that targets CDH6, a protein overexpressed in tumor cells. Participants will receive R-DXd through intravenous infusions. In Phase 2 (Part A), the dose will be optimized, and biopsies will be collected before and during treatment if possible. In Phase 3 (Part B), participants will be randomly assigned to receive either R-DXd or chemotherapy chosen by their doctor, which may include paclitaxel, topotecan, or PLD, all given by IV infusion. The study monitors treatment effects up to 18 months in Phase 2 and up to 26 months in Phase 3. During the study, participants will have regular scans and assessments to measure tumor response and progression-free survival. Researchers will monitor safety and organ function through lab tests and performance status evaluations. Participants must be willing to follow the study visits and procedures, which include biopsy samples in Phase 2 and imaging assessments to evaluate treatment response. The study aims to provide detailed information about how well R-DXd works and its safety in this patient group.

Researchers are investigating the use of raludotatug deruxtecan (R-DXd) monotherapy for patients with locally advanced or metastatic solid tumors that show various levels of cadherin-6 (CDH6) expression. This includes several gynecological cancers such as endometrial cancer, cervical cancer, and non-high-grade serous ovarian cancer, as well as genitourinary cancers like urothelial cancer and clear cell renal cell carcinoma (ccRCC). The study is a phase 2, multi-center, open-label trial focusing on evaluating the treatment's effectiveness and safety. Participants will receive raludotatug deruxtecan administered intravenously every three weeks. The trial includes different cohorts based on tumor type: for most cohorts except ccRCC, the main measure is the objective response rate evaluated by investigators using RECIST 1.1 criteria. For the ccRCC group, the primary measure is disease control rate. The study also monitors safety and tolerability across all groups. Treatment and assessments will continue up to 32 months from baseline. During the study, participants will undergo regular evaluations including imaging to measure tumor response, safety monitoring for any adverse events, and collection of biopsy samples before treatment begins. Researchers will track treatment-emergent adverse events, serious adverse events, and any adverse events of special interest. The study involves close follow-up and assessments to understand both the benefit and side effects of the treatment over an extended period, with total participation lasting up to 32 months.

Researchers are evaluating zolbetuximab combined with pembrolizumab and chemotherapy in adults with locally advanced, unresectable, or metastatic stomach or gastroesophageal junction (GEJ) cancer. This study focuses on cancer cells that are HER2-negative but positive for the Claudin 18.2 protein and PD-L1, exploring how well zolbetuximab helps the immune system attack the tumor alongside immunotherapy and chemotherapy. The trial is a phase 3, randomized, double-blind study designed to compare the overall survival of participants receiving zolbetuximab with pembrolizumab and chemotherapy versus those receiving a placebo with pembrolizumab and chemotherapy. Participants receive study treatment in 6-week cycles, with zolbetuximab or placebo given by infusion every 2 or 3 weeks. Chemotherapy regimens include either CAPOX (capecitabine tablets and oxaliplatin infusion) or mFOLFOX6 (infusions of 5-fluorouracil, folinic acid, and oxaliplatin) administered on schedules matching the cycles. Pembrolizumab is infused every 3 or 6 weeks. Treatment continues until cancer worsens, is not tolerated, or another therapy is needed, with pembrolizumab given for up to 2 years. After initial cycles, some chemotherapy drugs are adjusted to only include oral capecitabine or certain infusions. During the study, participants visit the clinic for treatments, health checks, and scans to monitor cancer changes and side effects. Researchers also track medical problems related to the treatments and may collect tumor samples if cancer worsens. After stopping treatment, participants have follow-up visits and scans every 9 to 12 weeks, along with telephone check-ins every 3 months. The primary outcome measured is overall survival up to 72 months, with ongoing monitoring to evaluate safety and treatment effects.

Researchers are evaluating new treatment options for people with proficient mismatch repair (pMMR) endometrial cancer (EC) that is advanced or has come back after prior treatment. This type of cancer starts in the lining of the uterus and is considered advanced when it has spread locally or to other body parts and cannot be removed by surgery. The study aims to compare the effectiveness of sacituzumab tirumotecan (sac-TMT), an antibody drug conjugate, combined with pembrolizumab versus pembrolizumab alone, to see which approach helps people live longer without the cancer worsening. Participants first receive an induction phase of six cycles, each lasting three weeks, of pembrolizumab combined with carboplatin and either paclitaxel or docetaxel through intravenous infusions. Those whose cancer does not progress after this phase enter the maintenance treatment phase, where they are randomly assigned to receive either pembrolizumab plus sac-TMT or pembrolizumab alone. If the cancer does progress, participants may enter a subsequent treatment phase and be randomly assigned to pembrolizumab plus sac-TMT or sac-TMT alone. During the study, researchers monitor participants for progression-free survival and overall survival for up to approximately 44 and 54 months, respectively. Participants undergo regular imaging, assessments, and laboratory tests to evaluate cancer status and treatment effects. The study also tracks safety and tolerability throughout all phases, providing a comprehensive follow-up to understand treatment impact over time.

Researchers are evaluating sacituzumab tirumotecan as a second-line treatment for female participants with recurrent or metastatic cervical cancer who have previously received platinum chemotherapy and anti-PD-1/PD-L1 therapy. This study has two phases: a safety run-in to assess the safety and efficacy of sacituzumab tirumotecan, followed by a Phase 3 portion comparing sacituzumab tirumotecan to treatment chosen by physicians. The study aims to determine if sacituzumab tirumotecan improves overall survival, especially in participants with high TROP2 expression. Participants will receive intravenous infusions of sacituzumab tirumotecan during the safety run-in phase. In the Phase 3 portion, participants are randomized to receive either sacituzumab tirumotecan or one of several physician-chosen treatments including pemetrexed, tisotumab vedotin, topotecan, vinorelbine, gemcitabine, or irinotecan, all given by IV infusion. This setup allows comparison of sacituzumab tirumotecan monotherapy against standard second-line therapies. Throughout the study, participants will undergo evaluations for tumor response, adverse events, and overall survival, with monitoring lasting up to approximately 51 months for the safety run-in and about 43 months for the Phase 3 portion. Researchers will use imaging and tumor tissue analysis to assess measurable disease and TROP2 expression. Safety and treatment tolerability will be closely observed, including tracking discontinuations due to adverse events.

Researchers are evaluating the safety and effectiveness of sacituzumab tirumotecan with or without bevacizumab compared to standard care in women with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer. This phase 3 study aims to learn how well patients tolerate these treatments and whether they live longer without their cancer worsening. The study focuses on those who have already undergone second-line platinum-based chemotherapy and have specific cancer stages and types. Participants receive sacituzumab tirumotecan and may also receive bevacizumab through intravenous infusion. Before sacituzumab tirumotecan, rescue medications such as H1 and H2 receptor antagonists, acetaminophen, dexamethasone, and steroid mouthwash are given to help manage side effects. The study includes multiple treatment phases and compares these interventions to standard care. These treatments are administered under close medical supervision throughout the study. During the study, participants are monitored for adverse events and treatment tolerability over approximately six weeks in the first part, followed by progression-free survival tracking for up to about four years. Assessments include physical exams, performance status evaluations, and safety monitoring. Researchers also collect tumor tissue samples and conduct laboratory tests to evaluate treatment effects. The total participation time involves ongoing observation to measure safety and effectiveness outcomes.

This research investigates the effectiveness and safety of combining capivasertib with CDK4/6 inhibitors and fulvestrant in adults with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer that is locally advanced, inoperable, or metastatic. It includes a Phase Ib dose-finding portion to establish safe dosages for the triple combination, followed by a Phase III study comparing this combination to CDK4/6 inhibitors plus fulvestrant alone. The study focuses on patients who have not received prior endocrine therapy for advanced disease and aims to assess added benefit in a high-risk population. During Phase Ib, participants receive capivasertib orally twice daily for 4 days followed by 3 days off each week, combined with fulvestrant injections and one of the CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) at varying doses to find the recommended dose for Phase III. In Phase III, participants are randomized to receive capivasertib plus fulvestrant and a CDK4/6 inhibitor at the established dose or fulvestrant plus a CDK4/6 inhibitor alone, with dosing schedules maintained over 28-day cycles. Participants undergo regular monitoring including scans for tumor assessment, blood tests, and safety evaluations over extended periods—up to 47 months for progression-free survival assessment. Researchers track adverse events, serious side effects, and treatment tolerability throughout. Mandatory tumor and blood samples are collected for biomarker analysis. The study evaluates key outcomes such as dose-limiting toxicities, treatment-related adverse events, and progression-free survival, supporting long-term safety and effectiveness evaluation.

Researchers are exploring a treatment approach for women with early-stage hormone receptor-positive, HER2-negative breast cancer who face an intermediate risk of cancer recurrence. This phase III trial builds on previous findings that adding the drug ribociclib, a CDK4/6 inhibitor, to standard hormone therapy after surgery can extend the time patients remain free from invasive disease. The study aims to see if using ribociclib allows some patients to avoid chemotherapy and its side effects without compromising treatment effectiveness. Participants will either receive chemotherapy followed by hormone therapy combined with ribociclib or a de-escalated treatment plan that reduces or omits chemotherapy while still using ribociclib and hormone therapy. Ribociclib will be administered for three years as part of the adjuvant treatment after surgery. The study is designed to reflect routine clinical practices for deciding chemotherapy eligibility, using standard pathological assessments and genomic tests. Throughout the trial, women will undergo regular monitoring, including clinical visits, laboratory tests, and heart function assessments, to ensure safety and treatment adherence. Researchers will measure invasive breast cancer-free survival over a period of up to 12 years from randomization. The study also tracks patients' ability to comply with treatment schedules and evaluates long-term outcomes to confirm if chemotherapy can be safely reduced or avoided in this group.