Subiaco

Researchers are evaluating the combination of BNT324, a B7-H3 antibody-drug conjugate, with BNT327, a bispecific antibody targeting PD-L1 and VEGF, in participants with advanced, metastatic, or relapsed small cell lung cancer SCLC and non-small cell lung cancer NSCLC. This multi-part study aims to find safe doses, optimize treatment, assess preliminary effects, and confirm clinical efficacy in different lung cancer groups. The study includes participants with confirmed lung cancer who have measurable disease and meet specific health criteria. Participants will receive intravenous infusions of BNT324 combined with BNT327 in a dose escalation design to establish two recommended dose levels RP2D and RP2D-1. The study has two parts Part 1 focuses on dose finding in NSCLC and SCLC Part 2 compares these doses in treatment-naive and relapsed lung cancer cohorts, with some randomized groups. Additional participants may join at the optimal dose to further evaluate safety and effectiveness. Participants will undergo screening, followed by treatment, safety follow-up, and long-term survival monitoring. Researchers will assess dose-limiting toxicities, adverse events, treatment interruptions, and response rates using standardized criteria. Outcomes include objective response rate, disease control, progression-free survival, duration of response, and overall survival, with evaluations continuing up to 87 months. Safety is closely monitored during and after treatment, and participants health status is regularly assessed.

Researchers are evaluating ONM-501, a drug given as intratumoral injections, alone and in combination with cemiplimab, an immune checkpoint inhibitor, in patients with advanced solid tumors and lymphomas. This phase 1 study aims to find the maximum tolerated dose, minimum effective dose, and recommended dose for expansion of ONM-501. The study includes patients with various advanced cancers who have no alternative standard therapies available. The trial has three parts monotherapy dose escalation, combination therapy dose finding, and combination therapy dose expansion. ONM-501 is given once per week for three weeks followed by three weeks off, in 21-day cycles. Cemiplimab is given intravenously every three weeks during the combination phases. Dose escalation uses special methods to gradually increase doses, and after doses are established, patients will enroll in expansion cohorts for specific tumor types. Participants will have regular assessments including monitoring for side effects, blood tests to measure drug levels, and evaluation of tumor response over up to 24 months. Researchers will track treatment-emergent adverse events, dose-limiting toxicities, and serious adverse events. Outcomes such as objective response rate, duration of response, progression-free survival, and overall survival will also be recorded. The study involves close safety monitoring and follow-up throughout the treatment and observation periods.

Researchers are assessing the survivorship and patient-reported outcomes after implantation of the Insignia hip stem in people undergoing cementless total hip replacement surgery. The study compares this new hip stem to currently available stems used for the same procedure, aiming to evaluate if the 2-year implant survivorship of the Insignia stem is not worse than the benchmark for similar devices. The trial focuses on patients with arthritis conditions such as osteoarthritis, degenerative joint disease, and rheumatoid arthritis. All participants will receive the Insignia hip stem prosthesis during their cementless total hip arthroplasty surgery. This surgery typically lasts about two hours and is performed by experienced orthopedic surgeons trained in this procedure. The study is conducted at multiple centers before the device is widely marketed. Data collection includes follow-up over two years to monitor implant survival and patient health outcomes. Participants will be involved in assessments before surgery and at 6 months, 12 months, and 2 years after surgery. These assessments include various hip function scores, pain scales, quality of life questionnaires, and monitoring for complications such as stem loosening or femoral fractures. Mortality rates at 1 and 2 years post-surgery will also be recorded. The study includes close monitoring for any adverse events related to the implant during the follow-up period.

This research aims to evaluate the effectiveness and safety of zanidatamab combined with a physicians choice of chemotherapy compared to trastuzumab combined with chemotherapy in treating adults with metastatic HER2-positive breast cancer who have either progressed on or cannot tolerate previous trastuzumab deruxtecan T-DXd treatment. Zanidatamab has shown promising results against various HER2-positive advanced tumors, including metastatic breast cancer, and may serve as a potential treatment option for these patients. The study also investigates patient-reported tolerability and physical functioning, as well as the pharmacokinetics and immune response to zanidatamab with chemotherapy. Participants will be randomly assigned to receive either zanidatamab or trastuzumab, each given by intravenous infusion alongside one of several chemotherapy options chosen by the physician eribulin, vinorelbine, gemcitabine, or capecitabine the latter is taken orally. Treatment will be administered according to the assigned group, and the study is open-label and multicenter, designed to compare these two treatment combinations in this patient population. During the study, participants will undergo regular assessments to monitor disease progression using imaging criteria RECIST version 1.1, evaluate survival, treatment response, and duration of response. Safety and side effects will be tracked through adverse event reporting and patient questionnaires on symptoms and physical function. Blood samples will be collected to study drug levels and immune reactions. Participants will be followed until disease progression, death, or for up to approximately 44 months for key outcomes, with overall survival monitored for up to about 80 months.

Researchers are evaluating the efficacy and safety of azenosertib ZN-c3, an oral drug that inhibits WEE1, in people with platinum-resistant, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. This Phase 2 study includes patients whose tumors test positive for Cyclin E1 protein. The study is designed to understand how azenosertib affects cancer cell growth by allowing damaged cells to continue the cell cycle, leading to cancer cell death. The study has two parts Part 1 included all patients regardless of biomarker status and has completed enrollment. Part 2 focuses on patients with Cyclin E1 positive tumors. Participants receive azenosertib orally at doses of either 300mg or 400mg daily, following a schedule of five days on treatment followed by two days off. Several study arms explore different dosing groups within this intermittent treatment plan. Participants will be monitored for up to approximately 12 months after the last patients enrollment. The study includes regular assessments of tumor response using RECIST criteria, measurement of biomarkers like CA-125, and tracking of side effects. Researchers will measure objective response rate as the primary outcome, along with duration of response, progression-free survival, clinical benefit rate, and treatment-emergent adverse events. This comprehensive monitoring aims to understand the treatments effects and safety profile over time.

Researchers are evaluating the effectiveness and safety of Ifinatamab Deruxtecan I-DXd compared to the treatment chosen by a physician for people with relapsed small cell lung cancer SCLC. This Phase 3 study aims to see if I-DXd can help participants live longer than current treatments, while also examining other effects such as patient-reported outcomes, immune response, and the drugs behavior in the body. Participants will be randomly assigned to one of two groups. One group will receive I-DXd as an intravenous infusion at a dose of 12 mgkg every 21 days until the disease worsens, unacceptable side effects occur, or other stopping reasons arise. The other group will receive one of the standard treatments chosen by their doctortopotecan, lurbinectedin, or amrubicinaccording to local approved dosing guidelines and until treatment discontinuation criteria are met. During the study, participants will be closely monitored with regular imaging and assessments to track tumor response, disease progression, and quality of life using questionnaires. Safety events and immune responses will also be recorded. Pharmacokinetic samples will be collected at specified times to understand how I-DXd behaves in the body. Participants may remain in the study for up to approximately 3.7 years, allowing for long-term evaluation of outcomes and safety.

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.

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 evaluating the efficacy and safety of ifinatamab deruxtecan I-DXd in adults with various recurrent or metastatic solid tumors. These tumor types include endometrial cancer, head and neck squamous cell carcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, hepatocellular carcinoma, adenocarcinoma of the esophagus, gastroesophageal junction and stomach, urothelial carcinoma, ovarian cancer, cervical cancer, biliary tract cancer, HER2-low and HER2 IHC 0 breast cancer, cutaneous melanoma, and neuroendocrine carcinoma. The study includes multiple phases to assess treatment effects and safety in these diverse groups. Participants receive I-DXd via intravenous infusion, typically dosed at 12 milligrams per kilogram, except in hepatocellular carcinoma where the dose is determined separately. The study is divided into three parts Stage 1, Stage 2, and an optional Stage 3 expansion for endometrial cancer, depending on safety and efficacy results. Each participant starts at Stage 1 and may continue to Stage 2 based on observed data. The hepatocellular carcinoma group includes a safety run-in phase to evaluate tolerability. Participants engage in regular assessments including imaging scans to measure tumor response and disease progression. Researchers monitor treatment-related side effects and collect blood samples to study how the drug behaves in the body over time. The studys main goal is to measure the objective response rate up to about 60 months after the first dose. Safety evaluations continue during treatment and for 47 days after the last dose. Participants may remain in the study for up to five years to track long-term outcomes and overall survival.