Norwich

This research aims to evaluate the safety and effectiveness of two dose levels of anvumetostat, a film-coated tablet, in participants with advanced non-small cell lung cancer (NSCLC) that has a specific genetic deletion called MTAP. The study is a Phase 2 trial focusing on participants who have previously been treated for their advanced NSCLC. It also assesses the treatment's effect through independent blinded review to better understand its impact on the cancer. Participants receive anvumetostat as a monotherapy, with dosing schedules tracked closely. The study includes detailed monitoring of drug levels in the blood at various times during treatment cycles to understand how the medicine is absorbed and processed. Treatment continues through several cycles, with specific days designated for blood sampling to measure drug concentration and timing. During the study, participants will be regularly assessed for tumor response using CT or MRI scans according to established criteria (RECIST 1.1). Researchers will also monitor the occurrence of any side effects or adverse events related to the treatment. The study period for measuring outcomes extends up to 35 months, allowing for long-term observation of safety, treatment response, and drug behavior in the body.

Researchers are evaluating a blood-based test called the Episwitch CiRT4, which maps 3D genome conformation, to predict how patients with stage III and IV cancer will respond to PD-(L)-1 immune checkpoint inhibitors. This test provides a binary likelihood of response (high vs. low probability) and aims to compare these predictions with actual treatment outcomes across multiple cancer types. The study also explores the relationship between social factors and test results or patient outcomes. Patients eligible for immune checkpoint inhibitor therapy will be offered the Episwitch CiRT4 test before starting treatment or while already receiving it. Those predicted to have a high probability of response will have repeat testing every three months. Participants will be followed for up to six months, during which treatment details and clinical outcomes such as disease-free survival, overall survival, stable disease, progressive disease, complete response, and time to recurrence will be collected. Throughout the study, researchers will gather comprehensive data on social determinants of health to analyze any connections to response likelihood or resistance. They will also collect physician questionnaires and patient-reported outcomes. The main outcomes include correlating the test's low probability predictions with actual responses, evaluating potential cost savings from avoiding ineffective therapies based on test results, and examining social factors influencing outcomes, all tracked from enrollment through the 24-week follow-up.

Researchers are evaluating treatments for people with extensive stage small-cell lung cancer (ES-SCLC). This phase 3 study compares the effectiveness of adding tarlatamab to a combination of durvalumab, carboplatin, and etoposide against the combination without tarlatamab. The main goal is to see which treatment better prolongs overall survival and progression-free survival over about 3.5 years. Participants receive intravenous infusions of the study drugs. One group gets tarlatamab combined with durvalumab, carboplatin, and etoposide, while the other group receives durvalumab, carboplatin, and etoposide alone. All treatments are given as first-line therapy for their lung cancer. During the study, participants will be monitored regularly to assess their response to treatment and overall health. Researchers will measure overall survival and progression-free survival to evaluate treatment benefit. The study also involves ongoing safety monitoring, and participants will be followed for up to approximately 3.5 years to collect these outcomes.

Researchers are evaluating the safety and effectiveness of targeted therapies and immunotherapy, alone or in combination, in people with metastatic colorectal cancer (mCRC) whose tumors show specific biomarkers. This open-label, exploratory Phase I/Ib study assigns participants to treatment groups based on their tumor biomarker test results. The goal is to understand how well these treatments work and how safe they are for different patient subgroups defined by biomarker status. Participants may receive various study drugs, including oral medications like Inavolisib, SY-5609, and Divarasib, or intravenous drugs such as Bevacizumab, Cetuximab, Atezolizumab, Tiragolumab, FOLFOX, and FOLFIRI. The specific treatment and schedule depend on the assigned study arm and the participant's biomarker profile. Biomarker testing is done using validated tests, including the FoundationOne Liquid CDx blood test, to guide treatment allocation. During the study, participants will be monitored for safety and treatment response over approximately 84 months, focusing on the objective response rate. Evaluations include tumor measurements using RECIST criteria, collection of tumor tissue samples for biomarker research, and regular assessments of organ function and overall health. Safety is closely tracked, and participants must be able to follow the study protocol and attend scheduled visits throughout their participation.

Researchers are comparing how long participants with KRAS/NRAS and BRAF wild-type recurrent, unresectable, or metastatic colorectal cancer remain disease-free and their overall survival time when treated with two different regimens. This phase 3 study focuses on patients who have previously received chemotherapy. The study aims to evaluate progression-free survival and overall survival in participants receiving amivantamab plus FOLFIRI versus cetuximab or bevacizumab plus FOLFIRI. The study involves two treatment groups: one receiving amivantamab combined with chemotherapy drugs 5-fluorouracil, leucovorin calcium or levoleucovorin, and irinotecan (FOLFIRI), and the other receiving either cetuximab or bevacizumab with the same chemotherapy regimen. Participants will be randomly assigned to one of these treatment arms. The treatments will be administered according to protocol to assess their effects on the cancer. Participants will be monitored for up to 2 years and 1 month to measure progression-free survival through blinded independent central review and followed for overall survival for up to 4 years and 4 months. The study includes assessments of tumor response, safety, and other clinical evaluations. Tissue samples and detailed clinical data will also be collected. This comprehensive monitoring will help determine the comparative effectiveness of the treatment options over time.

Researchers are evaluating nemtabrutinib compared with the investigator's choice of ibrutinib or acalabrutinib in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have not received any prior therapy. This Phase 3 study aims to determine if nemtabrutinib is not worse than ibrutinib or acalabrutinib in terms of objective response rate and if it is better regarding progression-free survival, both assessed using standardized disease criteria by independent review. Participants will be randomly assigned to receive one of the three oral treatments: nemtabrutinib, ibrutinib, or acalabrutinib. The study compares the effectiveness of nemtabrutinib against the other two drugs chosen by the investigator to treat first-line CLL/SLL. Treatment continues with monitoring over months to assess response and disease progression. During the study, participants will undergo evaluations based on the International Workshop on Chronic Lymphocytic Leukemia criteria, including blinded independent central reviews of their disease status. Researchers will track objective response rates up to about 33 months and progression-free survival up to around 104 months. Participants will also be monitored for safety and treatment adherence throughout the trial period.

Researchers are evaluating whether adding intismeran autogene to pembrolizumab after surgery can help people with non-small cell lung cancer (NSCLC) remain cancer-free longer compared to pembrolizumab with a placebo. This study focuses on patients with NSCLC whose tumors did not completely respond to treatment before surgery and aims to prevent the cancer from returning. It is a Phase 3 randomized, double-blind study involving participants with resectable Stage II to IIIB (N2) NSCLC. Participants receive treatments including pembrolizumab given as an intravenous infusion and either intismeran autogene or placebo administered as an intramuscular injection. Before surgery, patients have received neoadjuvant pembrolizumab combined with platinum-based doublet chemotherapy, but only those who did not achieve a complete pathological response are eligible. The study compares the effects of pembrolizumab with or without intismeran autogene following surgery. During the study, participants are closely monitored for disease-free survival over a period of up to approximately 97 months. Researchers will assess whether the cancer returns and evaluate overall safety. Participants undergo regular evaluations including clinical assessments and laboratory tests to monitor their health and treatment response throughout the study period.

Researchers are evaluating how well sonrotoclax combined with obinutuzumab or rituximab compares to venetoclax plus rituximab in treating adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This phase 3, open-label study will also assess the safety of these treatment combinations. The study is sponsored by BeOne Medicines, previously known as BeiGene, and involves multiple centers. Participants will receive one of the following treatments: sonrotoclax taken orally with intravenous obinutuzumab, sonrotoclax taken orally with intravenous rituximab, or venetoclax taken orally with intravenous rituximab. The treatments are given according to the study protocol, and participants are randomly assigned to one of these groups. The study monitors how these combinations work over time. During the study, participants will be regularly assessed through evaluations such as imaging, laboratory tests, and physical exams to monitor disease progression and treatment effects. Researchers will measure progression-free survival, which is how long participants live without disease worsening, with follow-up lasting up to about 51 months. Safety is also closely monitored to understand any side effects. The total duration of participation depends on the individual treatment and follow-up schedules.

Researchers are evaluating the maximum tolerated dose (MTD) and recommended combination dose of the PRMT5 inhibitor Anvumetostat when given with other therapies in adults with metastatic or locally advanced thoracic tumors that have a homozygous MTAP deletion. The study focuses on adults with thoracic tumors, including non-small cell lung cancer (NSCLC), to understand the safety and tolerability of these combinations. This is a Phase 1b study aiming to assess the safety profile of Anvumetostat combined with other treatments in this patient population. The study tests Anvumetostat administered orally alone or combined with intravenous therapies including carboplatin, paclitaxel, pembrolizumab, and pemetrexed, or oral sotorasib. Different treatment arms focus on specific histologies and biomarker statuses: one arm combines Anvumetostat with carboplatin, paclitaxel, and pembrolizumab for predominantly squamous NSCLC; another combines Anvumetostat with carboplatin, pemetrexed, and pembrolizumab for predominantly non-squamous NSCLC; a third arm combines Anvumetostat with pembrolizumab for PD-L1 positive tumors. A subgroup includes NSCLC patients with brain metastases meeting measurable disease criteria. Participants will be monitored for dose-limiting toxicities within approximately 21 days and for treatment-emergent and serious adverse events up to three years. Assessments include safety, tolerability, pharmacokinetics, and efficacy outcomes. Participants must provide tumor tissue samples or undergo biopsy if archival tissue is unavailable. The study evaluates disease status using RECIST v1.1 criteria and follows participants over time to track adverse events and treatment responses.

Researchers are evaluating the effectiveness of the Change4Better (C4B) mobile app in reducing the severity of problem gambling compared to standard treatment as usual (TAU). This 6-month randomized clinical trial involves individuals with gambling disorder who are either enrolled in or seeking outpatient treatment at facilities affiliated with the Bettor Choice Gambling Treatment Programs in Connecticut. The study aims to assess the feasibility and benefits of adding a cognitive behavioral therapy-based app to usual treatment. Participants will be randomly assigned to one of two groups: one receiving standard TAU alone and the other receiving TAU plus access to the Change4Better mobile app. The app provides cognitive behavioral therapy strategies targeting common concerns related to gambling, such as gambling debts and cognitive distortions about gambling outcomes. Participants can use the app as often as they wish on their own smartphones. Standard treatment is provided by outpatient clinics, and clinicians will continue their usual services without additional research duties. During the study, participants will be monitored for changes in gambling symptom severity from baseline to six months. Assessments include clinical interviews and self-reported measures of gambling behavior and severity. The research team will manage app access and support, and safety screening will identify participants with significant psychiatric or substance dependence concerns. Overall participation lasts six months, focusing on evaluating the app's impact alongside usual care.