Anchorage

Researchers are evaluating the efficacy and safety of ACR-368, an experimental drug, as a monotherapy or combined with ultra-low dose gemcitabine ULDG in participants with high-grade endometrial cancer. This open-label Phase 2 study divides participants into groups based on tumor sensitivity predicted by the OncoSignature Companion Diagnostic test or without requiring this test. The study aims to assess the anti-tumor activity of ACR-368 alone or with ULDG in different participant cohorts. Participants are assigned to one of four arms Arm 1 and Arm 4 receive ACR-368 alone, while Arm 2 and Arm 3 receive ACR-368 with ULDG sensitization. Arms 1 and 2 include participants selected based on OncoSignature results, while Arms 3 and 4 include those without this selection. Treatment continues until disease progression, unacceptable side effects, or withdrawal. European Union sites only enroll participants in Arms 3 and 4. Participants will be monitored every 8 weeks for tumor response using imaging for up to 2 years or until death. Safety assessments, including tracking of adverse events and pharmacokinetic testing, will be conducted throughout. Additional outcomes like overall survival, duration of response, and progression-free survival are evaluated. Participants must provide tumor tissue samples as required, and their organ function and general health will be assessed before and during the study.

Researchers are evaluating the use of pemigatinib for adults with advanced or metastatic pancreatic cancer that has spread locally or to distant parts of the body. This study focuses on patients whose cancer has specific abnormal changes in the FGFR gene, which can promote cancer growth. The goal is to see if pemigatinib can block these abnormal genes to stop tumor growth and improve quality of life. Participants take pemigatinib orally once daily for 14 days in each 21-day cycle, continuing as long as the cancer does not worsen or side effects are manageable. During the study, patients undergo blood tests, CT andor MRI scans, and optical coherence tomography OCT. Additional scans like whole body bone scans and eye exams may be performed if needed. After treatment, patients are followed up 30 days later and then every 4 months for one year. Throughout the study, researchers assess tumor response using imaging and blood tests, including monitoring cell-free DNA to track response and resistance. They measure overall response rate up to 24 months and evaluate progression-free survival, disease control, overall survival, and side effects up to 12 months. Safety and tolerability are closely monitored, and patients overall health and treatment effects are regularly checked to understand the impact of pemigatinib.

Researchers are evaluating the efficacy and safety of rilvegostomig combined with fluoropyrimidine and trastuzumab deruxtecan T-DXd compared to trastuzumab, chemotherapy, and pembrolizumab in patients with HER2-positive locally advanced or metastatic gastric or gastroesophageal junction GEJ adenocarcinoma whose tumors express PD-L1 CPS 1. A separate study arm will assess rilvegostomig combined with trastuzumab and chemotherapy to understand the contribution of each treatment component. This is a Phase 2, randomized, open-label, sponsor-blinded clinical trial conducted globally at about 200-250 sites in approximately 25 countries. Participants will be assigned to one of three treatment groups Arm A receives T-DXd, rilvegostomig, and fluoropyrimidine capecitabine or 5-FU Arm B receives pembrolizumab, trastuzumab, and chemotherapy 5-FU plus cisplatin or capecitabine plus oxaliplatin Arm C receives rilvegostomig, trastuzumab, and chemotherapy 5-FU plus cisplatin or capecitabine plus oxaliplatin. Most drugs are administered by intravenous infusion every three weeks, except capecitabine, which is given orally twice daily. The study compares the effects of these combinations as first-line treatments. Participants will be monitored for up to approximately six years to measure outcomes such as progression-free survival and overall survival. Other assessments include response rates, duration of response, adverse events, pharmacokinetics, immunogenicity, and impact on feeding and side effect burden. The study includes regular evaluations of tumor status using RECIST criteria, organ function, cardiac function, and collection of tumor tissue samples. Safety and treatment effects will be followed closely throughout the study duration.

Researchers are evaluating real-world patient characteristics, treatment methods, and long-term outcomes in people with symptomatic obstructive hypertrophic cardiomyopathy HCM in the United States and Europe. The study includes patients receiving mavacamten, other treatments, or no treatment due to intolerance or treatment failure. The US sub-study focuses on safety of mavacamten, while the European sub-study assesses both safety and effectiveness of mavacamten in everyday care. Participants may receive mavacamten or standard treatments like beta blockers, non-dihydropyridine calcium channel blockers, or disopyramide as prescribed by their doctors. The study observes these groups over time in routine clinical settings without altering their care. The study includes two main groups based on treatment type and monitors outcomes up to five years. Participants undergo evaluations including echocardiograms, heart function assessments using New York Heart Association NYHA class, left ventricular outflow tract gradient measurements, and patient-reported health questionnaires. Researchers also track heart failure events, arrhythmias, major cardiovascular events, hospitalizations, mortality, and biomarkers like NT-proBNP and cardiac troponin. Follow-up varies by region, lasting up to 18 months in Europe and up to 5 years in the United States.

Researchers are evaluating the effectiveness and safety of combining divarasib and pembrolizumab compared to pembrolizumab with pemetrexed and carboplatin or cisplatin for first-line treatment in adults with KRAS G12C-mutated advanced or metastatic non-squamous non-small cell lung cancer NSCLC. This phase III study focuses on patients who have not received prior systemic treatment for this type of lung cancer and aims to provide new options for this specific mutation. Participants are randomly assigned to one of two groups. One group receives an oral daily dose of divarasib along with pembrolizumab given by intravenous infusion every three weeks. The other group receives pembrolizumab combined with pemetrexed and either carboplatin or cisplatin, also administered intravenously every three weeks. Treatments continue according to the study schedule to assess how well each combination works and their safety profiles. Throughout the study, participants will be closely monitored for progression-free survival and overall survival for up to approximately five years. Additional assessments include tumor response, quality of life related to lung cancer symptoms, duration of response, and side effects reported by patients. Safety is also tracked by recording adverse events and their impact on daily activities. This comprehensive monitoring helps researchers understand the full effects of the treatments over time.

This research aims to gather long-term safety information from men with prostate cancer who have previously been treated with enzalutamide in an earlier study sponsored by Astellas or Medivation. The study focuses on participants who are still benefiting from enzalutamide treatment after the primary analysis or evaluation period of their prior trial has ended. Participants will continue taking the same treatment they received in their previous study, including enzalutamide once daily. Depending on which prior study they were part of, some may also take additional medications like abiraterone acetate with prednisone, or leuprolide acetate every 12 weeks alongside enzalutamide. Any dose changes require medical approval. The study also continued as a post-marketing clinical study in South Korea after local drug approval. During the study, participants will visit their institution every 24 weeks to review any side effects, medications, and confirm eligibility to continue. They will return every 12 weeks to return and receive study medication if applicable. Researchers will collect and monitor all adverse events, including serious ones, from consent until study completion, up to 96 months. This allows for thorough long-term safety monitoring while participants follow their usual care.

Researchers are investigating the best way to combine chemotherapy and radiation therapy for patients aged 3 to 29 years with localized non-germinomatous germ cell tumors NGGCT in the brain. This phase II trial aims to optimize treatment based on how well the tumor responds to initial chemotherapy, with the goal of reducing spinal cord relapses and adjusting therapy for better disease control. The study also compares different radiation types and examines cognitive and physical effects in children and young adults with NGGCT. Participants first receive induction chemotherapy consisting of carboplatin, etoposide, and ifosfamide over six cycles every 21 days. Based on tumor response, patients are assigned to one of two plans Plan A involves whole ventricular plus spinal canal irradiation WVSCI, delivered daily for 6 weeks, while Plan B includes high-dose chemotherapy with stem cell transplant followed by radiation therapy to the whole brain and spine. Some patients may undergo second-look surgery depending on tumor response before continuing treatment. Throughout the study, participants undergo MRI scans, collection of cerebrospinal fluid and blood samples, and questionnaires assessing cognitive, social, and behavioral functioning. Researchers monitor tumor response, progression-free survival, overall survival, and patterns of disease recurrence for up to 10 years. Safety and side effects are also evaluated to better understand long-term outcomes of these treatment approaches.

Researchers are evaluating camizestrant, an oral selective estrogen receptor degrader, compared to standard endocrine therapy in patients with early-stage ER-positive, HER2-negative breast cancer. This Phase III open-label study focuses on individuals at intermediate or high risk for disease recurrence who have completed locoregional therapy and at least 2 years, up to 5 years, of standard adjuvant endocrine therapy. The goal is to assess if camizestrant improves invasive breast cancer-free survival and other related outcomes. Participants are randomly assigned to receive either camizestrant or continue with standard endocrine therapy chosen by their investigator, which may include aromatase inhibitors such as exemestane, letrozole, anastrozole, or tamoxifen. Treatment duration for both groups is planned for 60 months 5 years. The study allows prior use of CDK46 inhibitors and excludes patients with specific medical conditions or prior use of similar investigational agents. During the study, patients will be regularly monitored for invasive breast cancer-free survival, invasive disease-free survival, distant relapse-free survival, overall survival, and safety measures, including adverse events and changes in laboratory and vital signs. Quality of life assessments related to symptoms like arthralgia, hot flushes, and vaginal dryness will also be conducted. Follow-up for participants will continue for up to 10 years from the last patients randomization.

Researchers are evaluating how well combination chemotherapy works in treating patients with newly diagnosed stages 2 to 4 diffuse anaplastic Wilms tumor DAWT and patients with relapsed favorable histology Wilms tumor FHWT. This phase II trial compares the effects of two chemotherapy regimens, UH-3 and ICECycloTopo, on event-free survival and overall survival, aiming to improve outcomes based on different relapse risk groups and prior treatments. The study also explores kidney toxicity, genetic markers, surgery impacts, and radiation therapy techniques to reduce side effects and better understand tumor behavior. Participants are assigned to one of two treatment groups. In Arm I Regimen UH-3, patients receive cycles of vincristine, doxorubicin, cyclophosphamide, carboplatin, etoposide, and irinotecan intravenously over various days in a 21-day cycle, with radiation therapy at week 7 of cycle 3 if needed. In Arm II Regimen ICECycloTopo, patients receive cycles of carboplatin, etoposide, ifosfamide, cyclophosphamide, and topotecan intravenously over 10 cycles every 21 days, with surgery andor radiation therapy during certain cycles as clinically indicated. Throughout the trial, patients undergo multiple imaging tests including CT scans, PET scans, chest x-rays, MRIs, abdominal ultrasounds, and bone scans, along with blood sample collections and biopsies. After completing treatment, follow-up visits occur every 3 months for the first 2 years, then every 6 months for years 3 and 4, and once at year 5. The main outcomes measured are event-free survival and overall survival up to 5 years from study entry, with ongoing monitoring for treatment effects and safety.

Researchers are evaluating the combination of intismeran autogene plus pembrolizumab compared to placebo plus pembrolizumab as adjuvant treatments for participants with margin negative, completely resected Stage II, IIIA, or IIIB with nodal involvement N2 non-small cell lung cancer NSCLC. The study aims to determine if intismeran autogene plus pembrolizumab improves disease-free survival DFS compared to placebo plus pembrolizumab. This is a phase 3, randomized, double-blind clinical trial sponsored by Merck Sharp Dohme LLC. Participants are randomly assigned to one of two groups one receives 1 mg of intismeran autogene by intramuscular injection every 3 weeks for 9 doses plus 400 mg of pembrolizumab by intravenous infusion every 6 weeks for up to 9 doses, and the other receives a placebo injection matching intismeran autogene on the same schedule plus pembrolizumab. Treatment continues until disease recurrence, unacceptable side effects, or approximately 1 year, whichever occurs first. During the study, participants will be closely monitored for disease-free survival over about 78 months and overall survival and lung cancer-specific outcomes for up to 12 years. Researchers will assess quality of life, physical and role functioning, breathlessness, coughing, chest pain, and record any adverse events or treatment discontinuations. The study includes long-term follow-up to evaluate safety and effectiveness outcomes.