Appleton

Researchers are evaluating the safety and effectiveness of combining durvalumab with domvanalimab compared to durvalumab with a placebo in adults who have locally advanced (Stage III), unresectable non-small cell lung cancer (NSCLC) that has not worsened after platinum-based concurrent chemoradiotherapy. This Phase III, randomized, double-blind, placebo-controlled international study aims to understand if adding domvanalimab improves outcomes in this patient group. Participants will receive either durvalumab plus domvanalimab or durvalumab plus placebo as intravenous infusions every four weeks, starting on Day 1, for up to 12 months. The study includes two groups: one receiving the experimental combination and the other receiving durvalumab with placebo. The treatment phase spans a maximum of one year. During the study, participants will be closely monitored through various assessments including tumor tissue analysis and performance status evaluations. Researchers will measure progression-free survival up to 8 years after randomization as the main outcome. Additional outcomes include overall survival, response rates, duration of response, and safety markers. The study involves long-term follow-up to assess durability of outcomes and treatment effects.

Researchers are conducting a prospective, longitudinal, non-interventional study involving participants with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC). The study focuses on molecular biomarker profiling using tissue and blood samples collected during participants' standard care treatment, aiming to enhance understanding of prognostic and predictive biomarkers over a five-year period. Participants planned for first-line immunotherapy or combination therapy will be included, with no additional interventions applied by the study. Up to 500 participants with tumors located in the pharynx, larynx, oral cavity, or oropharynx will be observed. Tissue samples representative of current disease and longitudinal blood samples will be collected to analyze DNA, RNA, immune, and other multiomic biomarkers. Throughout the study, participants will undergo biomarker assessments from blood and tumor tissue collected at diagnosis and progression. Researchers will explore changes in circulating tumor DNA (ctDNA) and other biomarkers to understand treatment responses and resistance mechanisms. The study will last up to five years, focusing on real-world outcomes and biomarker evolution during routine care without altering treatment plans.

Researchers are evaluating the combination of pembrolizumab and sacituzumab govitecan-hziy compared to standard chemotherapy treatments in patients with urothelial cancer that has spread locally or to other parts of the body. This phase III trial aims to assess overall survival, progression-free survival, response rates, clinical benefit, and treatment safety. The study also explores quality of life and fatigue changes during treatment to better understand patient experiences. Participants are randomly assigned to one of two groups. One group receives standard chemotherapy options such as carboplatin or cisplatin with gemcitabine, or alternatively docetaxel or paclitaxel, given intravenously in cycles every 21 days for up to six cycles. The other group receives pembrolizumab intravenously on day 1 and sacituzumab govitecan-hziy intravenously on days 1 and 8 of each 21-day cycle, continuing for up to 35 cycles or two years, unless the disease progresses or toxicity occurs. Both groups undergo blood sample collection and imaging scans like CT or MRI throughout the study. During the study, participants will have regular visits for treatment administration, blood tests, and imaging to monitor disease status and treatment effects. Researchers will collect data on survival, tumor response, side effects, and quality of life using questionnaires at multiple time points up to five years from the start of treatment. After finishing treatment, patients are followed up 30 days later and then once a year for five years to track long-term outcomes and safety.

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 CDK4/6 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 patient's randomization.

Researchers are studying repotrectinib (TPX-0005) in adults and adolescents with advanced solid tumors that have specific gene rearrangements in ALK, ROS1, or NTRK1-3. The trial aims to find the safest and most effective dose in Phase 1, and then evaluate how well the drug works in Phase 2 across different patient groups with these gene changes. This includes patients with tumors that have spread and those with brain involvement, focusing on response rates and survival outcomes. The study involves oral doses of repotrectinib. Phase 1 includes dose escalation to determine dose-limiting toxicities, maximum tolerated dose, and recommended dose for Phase 2. A sub-study also examines drug interactions with midazolam. In Phase 2, participants are assigned to one of six groups based on their tumor type and prior treatments, including different lines of targeted therapy and chemotherapy. Treatments continue according to protocol with regular monitoring. Participants will have measurable tumors confirmed by imaging reviewed centrally. They undergo physical exams, lab tests, and safety assessments throughout the study. Researchers measure response rates, duration of response, progression-free survival, overall survival, and clinical benefit over several years. The study monitors drug levels in blood and evaluates safety closely. Participation may last years with follow-up to assess long-term outcomes and effects on brain metastases.

Researchers are evaluating the addition of Tersolisib (LY4064809/STX-478) to other anti-cancer drugs as a first treatment for adults with advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer that has a specific genetic mutation called PIK3CA. This phase 3 study aims to assess both the effectiveness and safety of this combination treatment. Participants can remain in the study as long as the treatment is helping control the cancer without causing unbearable side effects. Participants will receive Tersolisib orally in combination with an oral CDK4/6 inhibitor and endocrine therapy (ET), which may be given orally or by intramuscular injection. The study includes different groups: one receiving two different doses of Tersolisib plus CDK4/6 inhibitor and ET, another receiving one dose of Tersolisib plus CDK4/6 inhibitor and ET, and a placebo group receiving placebo with CDK4/6 inhibitor and ET. The CDK4/6 inhibitors used include ribociclib, palbociclib, or abemaciclib, while ET options include anastrozole, letrozole, exemestane, or fulvestrant. During the study, participants will undergo evaluations that include measuring tumor response, progression-free survival, overall survival, and quality of life using questionnaires. Researchers will monitor participants regularly through scans, lab tests, and clinical assessments to track treatment response and side effects. The study may last up to 7 years to observe long-term outcomes, and participants will be closely followed to assess how the cancer responds and how the treatments affect their health and well-being over time.

Researchers are evaluating whether adding the immunotherapy drug durvalumab to the usual chemotherapy treatment can improve outcomes for adults with MammaPrint High 2 Risk (MP2) stage II-III hormone receptor positive, HER2 negative breast cancer. This phase III trial compares standard chemotherapy alone to chemotherapy combined with durvalumab. Previous evidence suggests patients with this specific cancer profile may respond better to chemotherapy and immunotherapy, so this study aims to see if durvalumab helps prevent cancer from returning. Participants are first screened with MammaPrint testing on tumor tissue to confirm MP2 status. Those eligible are then randomly assigned to one of two treatment groups. One group receives paclitaxel intravenously on days 1 and 8 every 14 days for 6 cycles, followed by doxorubicin and cyclophosphamide every 14 days for 4 cycles. The other group receives the same chemotherapy schedule plus durvalumab intravenously during specific cycles. Mammography is done during screening, and optional tumor tissue and blood samples are collected throughout the study. During the trial, participants undergo regular assessments including mammograms, tissue biopsies, and blood tests to monitor response and safety. Researchers measure event-free survival, pathologic complete response, residual cancer burden, distant relapse-free survival, and overall survival for up to 10 years after treatment. Quality of life is also evaluated through questionnaires during and after treatment. Participants are followed long-term to track outcomes and side effects.

Researchers are evaluating camizestrant, a new oral drug, compared to standard adjuvant endocrine therapies for patients with early breast cancer that is estrogen receptor positive and HER2 negative. This trial focuses on patients at intermediate-high or high risk for the cancer returning who have completed local treatments like surgery, with or without chemotherapy. The study is a Phase III open-label trial sponsored by AstraZeneca, aiming to see if camizestrant improves invasive breast cancer-free survival over a planned treatment duration of seven years. Participants will be randomly assigned to one of two treatment groups: one receiving standard endocrine therapy chosen by the doctor (including aromatase inhibitors such as exemestane, letrozole, or anastrozole, or tamoxifen) with or without abemaciclib, and the other receiving camizestrant with or without abemaciclib. Treatments are taken orally, and both groups are followed for up to 10 years from the last patient's randomization to monitor outcomes and safety. During the study, participants will have regular assessments to monitor invasive breast cancer-free survival, overall survival, and other outcomes like distant relapse-free survival and quality of life. Safety evaluations include tracking side effects using established criteria and patient-reported measures. Pharmacokinetics of camizestrant will be studied for six months, with adverse events monitored up to 28 days after the last treatment dose. The total involvement can last up to 14 years including treatment and follow-up periods.

Researchers are studying the effects of NGM120 in people with colorectal cancer who also have cancer cachexia, a condition involving significant weight loss. This is a Phase 2, randomized, double-blind, placebo-controlled study conducted at multiple centers to assess the safety, tolerability, and potential benefits of NGM120 in this population. Participants will receive either NGM120 or a placebo through subcutaneous injections. NGM120 is given in different dosing schedules: low dose every 4 weeks, high dose every 4 weeks, or high dose every 8 weeks. Placebo is administered every 4 weeks. These treatments will be compared to evaluate differences. Throughout the study, participants' body weight changes will be monitored for 12 weeks to assess treatment impact. Safety will be evaluated by tracking adverse events over 44 weeks. Participants will undergo regular assessments, including monitoring for treatment effects and side effects, with the total study duration extending up to 44 weeks.

Researchers are evaluating the addition of olaparib, a targeted therapy that blocks the PARP enzyme involved in DNA repair, in patients with pancreatic cancer who have had surgery to remove their tumor and carry a mutation in BRCA1, BRCA2, or PALB2. This phase II trial aims to determine if olaparib can improve relapse-free survival compared to placebo after chemotherapy completion. The study also explores overall survival and differences based on mutation type and chemotherapy received. Participants are randomly assigned to one of two groups. One group receives oral olaparib twice daily for 28-day cycles, up to 12 cycles, while the other group receives a placebo on the same schedule. Throughout treatment, patients undergo CT or MRI scans and blood collection. After treatment, patients are followed for up to 10 years with regular visits to monitor health and disease status. During the study, participants complete imaging scans and blood tests to assess disease progression and treatment effects. Researchers track relapse-free survival from the time of randomization until disease recurrence or death, with assessments extending up to 44 months. Safety and survival outcomes are monitored for up to 10 years. Follow-up visits occur 30 days after treatment and then every 4 months in the first year, followed by every 6 months for years 2 through 10.