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Researchers are evaluating two different methods of pacing the heart in patients with slow heart rates (bradycardia). This multi-center randomized controlled trial, called PROTECT-HF, aims to compare the standard right ventricular pacing approach with a newer physiological pacing technique, which includes His bundle and left bundle area pacing. The study will enroll 2600 patients to assess differences in outcomes related to heart function and survival. Participants will be randomly assigned to receive either right ventricular pacing or physiological pacing through pacemaker implantation. The physiological pacing method may involve His bundle pacing or left bundle pacing, with biventricular pacing used if these are not possible. Both treatments will be performed at participating centers, with patients and outcome assessors blinded to the treatment allocation. A subgroup of 500 patients will also take part in an optional echocardiographic sub-study to observe heart changes over 24 months. During the study, participants will be monitored from the time of consent for up to 78 months. Evaluations will occur at the start and every six months afterward to track mortality and heart failure-related health events. Researchers will gather data on heart function, treatment effects, and safety. The main analysis will consider all patients as originally assigned, and additional analysis will assess those who received the assigned treatment.

Researchers are evaluating amivantamab, an investigational drug, in patients with high-grade malignant brain tumors, specifically glioblastoma multiforme (GBM) and related molecular subtypes. This Phase 1b trial aims to assess the safety, tolerability, and preliminary antitumor activity of amivantamab when given at the recommended Phase 2 dose. The study is part of the Minderoo 5G platform, focusing on biomarker-guided therapies for patients with molecularly defined brain tumors characterized by EGFR amplification and other genetic markers. Amivantamab is given as an intravenous infusion weekly for the first 4 weeks, followed by every 2 weeks until disease progression or unacceptable side effects occur. The initial dose is split over two days to improve tolerance, starting with 350 mg over 4 hours and then 1400 mg over 6 hours. Subsequent doses are 1750 mg over 2-5 hours in the first cycle and 2-3 hours thereafter if well tolerated. The trial includes an adaptive design with decision points led by a Safety Review Committee to guide further study steps and progression to Phase 2 depending on emerging data. Participants will undergo regular evaluations including clinical assessments, laboratory tests, and imaging to monitor tumor response and safety over an 18-month period. Researchers will measure safety outcomes and preliminary efficacy using established criteria for tumor response. Patients must meet specific eligibility criteria related to diagnosis, previous treatments, and general health status. The study also includes monitoring for side effects and adherence to study protocols throughout participation.

Researchers are evaluating the safety, tolerability, and preliminary antitumour activity of the investigational drugs avutometinib and defactinib in patients with malignant brain tumors, specifically glioblastoma and other molecularly defined high-grade brain tumors. This Phase 1/2 trial is part of the Minderoo 5G platform and includes biomarker-guided treatment arms targeting tumors with specific genetic features such as hyperactivating BRAF mutations or NF1 loss. The study uses a Bayesian multi-arm, open-label, adaptive design for efficient hypothesis testing and patient assignment. In the Phase 1b portion, patients with relapsed glioblastoma multiforme (GBM) receive double therapy with oral avutometinib at 3.2 mg twice weekly (total 6.4 mg per week) and oral defactinib at 200 mg twice daily (total 400 mg per day). Treatment arms progress to Phase 2 upon meeting predefined success criteria, where efficacy is tested in the front-line minimal residual disease setting. Phase 2 may involve doublet therapy or triplet therapy adding temozolomide capsules, given either concurrently or sequentially based on emerging data and safety review committee decisions. Participants undergo screening and assessments including molecular tumor profiling, neurological evaluations, and laboratory tests before and during treatment. Researchers monitor safety, tolerability, and tumor response over 9 to 12 months depending on the phase. The trial includes ongoing safety reviews and adaptive decision points to guide treatment continuation or modification. Participant involvement includes oral medication administration, clinical follow-up, and data collection on tumor activity and side effects throughout the trial duration.

Researchers are evaluating whether an investigational drug called OHB-607 can prevent Bronchopulmonary Dysplasia (BPD), a common chronic lung disease, in extremely premature infants. The study compares infants receiving OHB-607 alongside standard neonatal care to those receiving standard care alone to reduce the burden of this lung condition. This is a Phase 2b, multicenter, randomized, open-label study focused on safety and clinical efficacy. Participants will receive an intravenous infusion of OHB-607 from birth until reaching a postmenstrual age (PMA) of 29 weeks and 6 days. The study includes two arms: one group receives the investigational drug plus standard care, while the other group receives only standard neonatal care. The treatment period ends at 29 weeks plus 6 days PMA, after which infants are monitored. Throughout the study, researchers will track the incidence of severe BPD or death up to 36 weeks PMA, whichever occurs first. Assessments will include clinical evaluations and monitoring for safety and any side effects. The study also involves long-term follow-up to observe the infants' health outcomes beyond the treatment period. Participation involves consent from parents and collection of birth and medical history information.

Researchers are evaluating the safety and effectiveness of ifinatamab deruxtecan (I-DXd) alone or combined with other treatments in people with metastatic castration-resistant prostate cancer (mCRPC). This study aims to understand how well patients tolerate the treatment, find a safe dose for combining I-DXd with other drugs, and measure prostate-specific antigen (PSA) levels during treatment. The study is part of a larger master screening protocol and includes patients with confirmed prostate adenocarcinoma who have progressive disease despite prior therapies. Participants receive treatments including I-DXd given through intravenous infusion, sometimes combined with other drugs such as docetaxel (IV), MK-5684, abiraterone, or enzalutamide (all oral). Before each I-DXd dose, patients take premedication to prevent nausea and vomiting. The study includes both a safety lead-in phase and an efficacy phase, with ongoing monitoring for side effects and tolerability. The combination therapies are carefully dosed and scheduled according to the study protocol. During the study, participants undergo regular assessments to monitor side effects, measure PSA response, and track any dose-limiting toxicities. Safety is closely followed, particularly during the first 21 days for combination treatments, and throughout up to 54 months for long-term outcomes. Researchers also observe if participants discontinue treatment due to adverse events. The study requires ongoing visits and evaluations to ensure participant health and collect data on treatment effects over time.

Researchers are evaluating sotatercept as a potential treatment for pulmonary arterial hypertension (PAH), a condition where blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and overworking the heart. PAH symptoms include difficulty breathing and reduced ability to be active. Current standard treatments address symptoms but do not stop disease progression. This Phase 3 study focuses on the long-term safety and tolerability of sotatercept when added to standard PAH therapy. Participants in this long-term follow-up study receive sotatercept through subcutaneous injections every three weeks. Only individuals who completed prior sotatercept PAH studies without early discontinuation may join. This study continues the observation and assessment of participants over an extended period to learn about the effects and safety of sotatercept combined with background PAH treatments. During the study, participants will be regularly monitored for adverse events, treatment discontinuations, and the presence of anti-drug antibodies for up to approximately 90 months. Laboratory tests will evaluate blood components such as platelets, hemoglobin, creatinine, bilirubin, and liver enzymes. Changes from baseline in body weight, blood pressure, and electrocardiogram readings will also be tracked. The study involves adherence to visit schedules and compliance with study procedures to ensure comprehensive long-term safety data collection.

Researchers are investigating treatments for women with recurrent endometrial cancer that expresses different levels of the HER2 protein. The study has two groups based on the tumor's HER2 score: Cohort 1 includes patients with HER2 IHC 1+ or 2+ who have previously received immune checkpoint inhibitors and platinum-based chemotherapy, while Cohort 2 includes patients with HER2 IHC 3+. The purpose is to compare the effectiveness and safety of the investigational drug BNT323 (also called DB-1303) against chemotherapy in Cohort 1 and to evaluate BNT323 alone in Cohort 2. The study also looks at how the drug affects the immune system, the body's handling of the drug, quality of life, and potential side effects. Participants in Cohort 1 are randomly assigned to receive either BNT323 via intravenous infusion or a chemotherapy drug chosen by the investigator (doxorubicin, paclitaxel, or docetaxel if paclitaxel is unsuitable). Treatment continues until the cancer progresses, unacceptable side effects occur, or the participant withdraws consent. Those in Cohort 2 receive BNT323 alone until disease progression or other discontinuation criteria are met. The study includes a screening period, a treatment period expected to last about six months, followed by safety monitoring, efficacy follow-up, and long-term survival follow-up lasting up to approximately 53 months. During the study, participants undergo regular assessments including imaging scans to measure tumor response by RECIST criteria, safety monitoring for adverse effects, and evaluations of quality of life. Researchers also study the pharmacokinetics of BNT323 and the immune response. The main outcomes measured are progression-free survival in Cohort 1 and objective response rate in Cohort 2. Safety follow-up ensures ongoing monitoring after treatment to evaluate longer-term effects and participant wellbeing.

Researchers are conducting a Phase I/II, multi-site, open-label study to evaluate the safety, effectiveness, and optimal dosing of the investigational treatments BNT323 combined with BNT327 in adults with advanced breast cancer. This includes those with hormone receptor-positive or negative types, HER2-positive, HER2-low, HER2-ultralow, HER2-null breast cancer, or triple-negative breast cancer. The study aims to understand how these treatments work alone and together in this patient population. The study has two parts: Part 1 involves dose escalation where participants with chemotherapy-pretreated advanced breast cancer receive BNT323 and BNT327 together to find the recommended Phase 2 dose. Part 2 is an expansion phase that tests the safety and effectiveness of the chosen dose, including randomized comparisons of combination therapy at different doses and monotherapies. Participants may be assigned to one of four treatment arms, with dosing administered via intravenous infusion. Participants will be monitored for dose-limiting toxicities during the first 21 days of treatment, as well as adverse events up to 90 days after the last dose. Tumor response will be assessed for up to 36 months. Evaluations include heart function tests, tumor imaging, safety assessments, and tracking of side effects. The study carefully monitors treatment safety, effectiveness, and participant health throughout the trial duration.

Researchers are evaluating the safety, tolerability, and therapeutic effects of a combination treatment using BNT113 and pembrolizumab compared to pembrolizumab alone for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that is positive for human papillomavirus 16 (HPV16+) and expresses the PD-L1 protein with a combined positive score of 1 or higher. This Phase II/III trial includes patients whose cancer cannot be treated with local therapies and who have not received prior systemic anticancer therapy for their current disease condition. The trial consists of two parts. Part A is a non-randomized Safety Run-In Phase to confirm the safety and tolerability of BNT113 combined with pembrolizumab at the selected dose. Part B is a randomized phase that compares BNT113 plus pembrolizumab against pembrolizumab alone as first-line treatment. Patients in Part A continue their treatment without randomization. Treatments are given by intravenous injection or infusion, and patients may receive either combination therapy or monotherapy for up to 24 months. There is also an optional pre-screening phase to test tumor samples for HPV16 DNA and PD-L1 expression before entering the main trial. Participants undergo regular assessments including tumor measurements based on RECIST 1.1 criteria confirmed by independent review. Researchers monitor treatment-emergent adverse events for up to 27 months in Part A and evaluate overall survival and progression-free survival for up to 48 months in Part B. Tumor tissue samples are collected before treatment to confirm eligibility. The study involves ongoing safety monitoring and efficacy evaluations throughout the treatment and follow-up periods.

Researchers are evaluating AZD8421, a CDK2 inhibitor, alone and combined with other targeted anti-cancer drugs in female patients with ER+ HER2- advanced breast cancer and metastatic high-grade serous ovarian cancer. This Phase I/IIa study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary effectiveness of AZD8421. The study includes patients previously treated with CDK4/6 inhibitors or platinum-based chemotherapy, focusing on those with progressing metastatic or locoregionally recurrent disease. The study includes two main parts: AZD8421 monotherapy and combination therapy. Monotherapy evaluates AZD8421 alone to find the recommended Phase II dose in patients with advanced breast or ovarian cancer. Combination therapy tests AZD8421 with a CDK4/6 inhibitor (abemaciclib, ribociclib, or palbociclib) and camizestrant, an oral SERD, in breast cancer patients previously treated with CDK4/6 inhibitors. Treatment safety and drug behavior are closely monitored throughout. Participants will undergo assessments for dose limiting toxicities and adverse events from treatment start through an approximately 18-month safety follow-up. Researchers will also monitor laboratory tests, vital signs, ECGs, and reasons for stopping AZD8421 due to toxicity. The study requires measurable or assessable tumor lesions and performance status evaluations, ensuring patients meet specific health criteria. Total participation duration includes treatment and extended safety monitoring.