Gqeberha

Researchers are investigating new treatments for people with high-risk, early-stage breast cancer, specifically targeting triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/HER2-negative breast cancer. These types have little or no HER2 protein and involve hormones like estrogen or progesterone. The study aims to evaluate if the addition of sacituzumab tirumotecan (sac-TMT), a targeted therapy, combined with pembrolizumab and chemotherapy can improve outcomes compared to pembrolizumab with chemotherapy alone. Participants receive treatments including sacituzumab tirumotecan, pembrolizumab, and chemotherapy drugs such as carboplatin and paclitaxel, all given by intravenous infusion. Rescue medications like antihistamines, acetaminophen, dexamethasone, or steroid mouthwash may be used as needed. The study is randomized and open-label, comparing sac-TMT followed by chemotherapy plus pembrolizumab to chemotherapy and pembrolizumab without sac-TMT. During the study, researchers will monitor participants up to about 30 weeks to assess the percentage of people with no remaining cancer cells at surgery. They will also follow participants for up to approximately 92 months to track event-free survival, meaning time without cancer growth, spread, or return. Participants will undergo imaging, clinical assessments, and laboratory tests to evaluate treatment effects and safety throughout the study.

Researchers are evaluating the effectiveness and safety of opevesostat combined with hormone replacement therapy compared to alternative treatments with abiraterone acetate or enzalutamide in people with metastatic castration-resistant prostate cancer (mCRPC) who have already been treated with one next-generation hormonal agent. This Phase 3 study aims to determine whether opevesostat improves radiographic progression-free survival, assessed by independent central review, in participants with or without androgen receptor ligand binding domain mutations. Participants will receive either oral opevesostat along with hormone replacement therapy drugs such as dexamethasone and fludrocortisone acetate, or they will receive alternative oral treatments including abiraterone acetate with prednisone acetate or enzalutamide. Hydrocortisone can be used as a rescue drug if needed. The study is open-label and randomized, comparing these treatment strategies in participants who have progressed after prior hormonal therapy. During the study, participants will undergo assessments including imaging scans to monitor disease progression. Researchers will measure radiographic progression-free survival up to approximately 52 months. Safety and overall survival are also monitored as secondary outcomes. Participants must attend scheduled visits for evaluations, provide tumor tissue samples, and have ongoing monitoring of organ function, hormone levels, and other relevant health parameters throughout the study period.

Researchers are evaluating quabodepistat-based treatment regimens for adults and adolescents aged 14 years and older with rifampicin-resistant or multidrug-resistant pulmonary tuberculosis (RR/MDR-TB). This Phase 3, randomized, open-label, multicenter trial aims to determine if quabodepistat combined with other tuberculosis drugs can shorten treatment to 4 months and offer similar or better effectiveness and safety compared to the current 6-month WHO-recommended treatments. The study includes two main groups based on fluoroquinolone sensitivity: fluoroquinolone-sensitive and fluoroquinolone-resistant RR/MDR-TB. Participants will be randomly assigned to receive either experimental or control treatments. For fluoroquinolone-sensitive RR/MDR-TB, the experimental regimen is BPaQM (bedaquiline, pretomanid, quabodepistat, moxifloxacin) for 4 months, compared to the control BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) for 6 months. For fluoroquinolone-resistant RR/MDR-TB, the experimental treatment is BPaQ (bedaquiline, pretomanid, quabodepistat) for 6 months, versus the control BPaL (bedaquiline, pretomanid, linezolid) for 6 months. Drug dosing schedules vary by regimen, with bedaquiline dosing starting with daily doses followed by maintenance doses and all other drugs dosed once daily. Participants will be followed for 16 months after randomization, during which time researchers will assess treatment effectiveness by measuring the proportion of participants with unfavorable outcomes up to 12 months following randomization. Safety and tolerability will be monitored through recording adverse events from the first dose until two weeks after treatment ends. The study includes sputum sample collection, chest X-rays, laboratory tests, and monitoring for side effects. Independent committees oversee data monitoring and outcome adjudication to ensure participant safety and study integrity.

Researchers are evaluating sacituzumab tirumotecan alone and combined with pembrolizumab compared to the treatment chosen by a physician for people with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer that cannot be removed by surgery or has spread to other parts of the body. This study focuses on participants whose cancer has progressed despite prior endocrine therapy, including treatment with a CDK4/6 inhibitor. The main goal is to see if these treatments improve progression-free survival, which means the length of time the cancer does not worsen, over up to approximately 38 months. Participants receive sacituzumab tirumotecan as an intravenous infusion, either alone or combined with intravenous pembrolizumab. The comparison group receives the treatment of physician's choice, which may include intravenous paclitaxel, nab-paclitaxel, liposomal doxorubicin, or oral capecitabine. The study is open-label and randomized, meaning participants are assigned to different treatment groups openly. Treatments are administered according to the study protocols, with ongoing monitoring during the treatment period. Throughout the study, participants are monitored regularly to assess their cancer status and overall health. This includes evaluations by blinded independent central review using RECIST 1.1 criteria to measure tumor progression. Researchers also assess safety, organ function, and performance status. The total participation time may last up to around 38 months to track progression-free survival and other outcomes. Careful monitoring helps ensure participant safety and collects data on treatment effectiveness and side effects.

Researchers are evaluating the pharmacokinetics, efficacy, safety, and immune response of MB12, a proposed pembrolizumab biosimilar, compared to Keytruda® in patients with advanced stage IV non-squamous non-small cell lung cancer (NSCLC). This Phase 3, randomized, double-blind study involves patients who have not received prior systemic treatment for metastatic NSCLC and includes a range of international centers. The trial focuses on patients without EGFR activating mutations or ALK translocations and measures outcomes up to 24 weeks. Participants receive either MB12, EU-sourced Keytruda®, or US-sourced Keytruda®, each given as a 200 mg intravenous infusion every 3 weeks on Day 1. These immunotherapy drugs are combined with chemotherapy agents pemetrexed (500 mg/m2 IV every 3 weeks on Day 1) and either carboplatin (area under the curve 5 IV every 3 weeks on Day 1 for 4 cycles) or cisplatin (75 mg/m2 IV every 3 weeks on Day 1 for 4 cycles). The combination treatment is administered as a first-line therapy for metastatic NSCLC. During the study, patients are monitored for drug levels in the blood, treatment effectiveness, safety, and immune response. Regular assessments include imaging to measure tumor lesions using RECIST 1.1 criteria and evaluations of overall health and organ functions. The study aims to confirm that MB12 is similar to Keytruda® in how it is processed by the body and in its treatment results. Participants are followed for at least 24 weeks to collect data on these outcomes.

This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor (palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant endocrine therapy.

Researchers are evaluating the combination of the investigational drug PF-06821497 (mevrometostat) with enzalutamide compared to enzalutamide alone in men with metastatic castration-resistant prostate cancer (mCRPC) who have not previously received androgen receptor signaling inhibitors (ARSi) or abiraterone. This global, multicenter Phase 3 study focuses on participants whose cancer has progressed despite androgen deprivation therapy (ADT) or first-generation anti-androgens but who have not started other systemic anti-cancer treatments for mCRPC. The study excludes those with prior treatment using enzalutamide, darolutamide, apalutamide, or abiraterone in any setting, though chemotherapy is allowed in the hormone-sensitive setting. The study includes a Screening Phase, followed by randomization where participants are assigned equally to one of two groups: one receiving PF-06821497 plus enzalutamide, and the other receiving placebo plus enzalutamide. All treatments are taken orally on a continuous basis. After the treatment phase, participants enter a Safety Follow-up and a Long-Term Follow-up period to monitor ongoing effects. Participants will undergo assessments during the study to evaluate radiographic progression-free survival over about three years. Researchers will collect imaging data such as bone scans and CT or MRI scans to monitor disease progression. Additional evaluations include performance status, life expectancy assessments, and safety monitoring for adverse events. The study duration spans from screening through treatment and follow-up phases to gather comprehensive data on the combination therapy's impact on mCRPC.

This is a Phase III open-label study to assess if camizestrant improves outcomes compared to standard adjuvant endocrine therapy for patients with ER+/HER2- early breast cancer with intermediate-high or high risk for disease recurrence who completed definitive locoregional therapy (with or without chemotherapy). The planned duration of treatment in either arm of the study is 7 years. Eligible patients must have intermediate-high or high risk of recurrence as defined by specified clinical and biologic criteria. Concurrent use of abemaciclib is permitted in both arms. The primary endpoint of the study is Invasive breast cancer-free survival (IBCFS) and main secondary endpoints include Invasive disease-free survival (IDFS), Distant relapse-free survival (DRFS), Overall survival (OS), Safety and Clinical Outcome Assessments (COAs). Patients will be followed for 10 years from randomization of the last patient.

Researchers are evaluating a nurse-led treatment approach for rifampicin-resistant tuberculosis (RR-TB) in primary care clinics compared to the standard physician-led treatment at district hospitals in South Africa. This multi-site, cluster randomized, non-inferiority trial spans five years and aims to assess treatment outcomes, safety, and patient costs. The study includes participants from KwaZulu-Natal, Gauteng, and Eastern Cape provinces and considers patients regardless of HIV status. The trial compares nurse-led RR-TB care delivered in primary care clinics, where nurses visit once or twice weekly on a rotating schedule, to physician-led outpatient care in hospitals. This approach aims to create equal access and management responsibilities between the two models. The nurse-led care model is designed to be patient-centered and closer to patients' homes, following World Health Organization recommendations for decentralized treatment of RR-TB with six-month regimens. Participants will be closely monitored throughout the study, with assessments covering treatment outcomes at six months, safety through severe adverse events over twelve months, and evaluation of patient-related catastrophic costs within a year. Researchers will also examine treatment initiation times, microbiological conversion, HIV treatment progress, adherence to dosing guidelines, and cost-effectiveness. The study involves thorough clinical and laboratory evaluations, including access to necessary labs, X-rays, and ECGs, with ongoing safety and effectiveness monitoring over the trial duration.

Researchers are evaluating the effectiveness and safety of two oral drug combinations, Bemnifosbuvir-Ruzasvir (BEM/RZR) and Sofosbuvir-Velpatasvir (SOF/VEL), in adults with chronic Hepatitis C virus (HCV) infection. This Phase 3 trial compares these treatments to determine which is better at reducing the virus in the blood. Participants include adults aged 18 to 85 years, including those with compensated liver cirrhosis, and some with controlled HIV-1 infection under specific treatment conditions. Participants will receive either BEM/RZR tablets once daily for 8 weeks if they do not have cirrhosis, or for 12 weeks if they have compensated cirrhosis. Those in the comparison group will take SOF/VEL tablets once daily for 12 weeks. The study is randomized, controlled, and open-label, meaning both participants and researchers know which treatment is given. During the study, researchers will monitor patients to see how many achieve very low levels of HCV RNA in their blood by week 24. The study will include regular medical assessments, safety monitoring, and evaluation of treatment adherence. Participants will be followed from the start of treatment until 24 weeks later to assess outcomes and any side effects.