Barretos

Researchers are studying treatments for locally advanced or metastatic colorectal cancer mCRC that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This trial aims to evaluate if adding the targeted therapies calderasib and cetuximab to the standard chemotherapy regimen mFOLFOX6 can provide better outcomes compared to mFOLFOX6 with or without bevacizumab. The study focuses on the safety and tolerability of these combinations and whether they can help people live longer without their cancer growing or spreading. Participants will be assigned to one of two groups. One group will receive calderasib orally, cetuximab every two weeks, and mFOLFOX6 chemotherapy including oxaliplatin, leucovorin or levofolinate calcium, and 5-fluorouracil every two weeks. The other group will receive mFOLFOX6 chemotherapy with or without bevacizumab every two weeks, based on the investigators decision. Treatments will continue until certain stopping criteria are met. During the study, participants will be monitored for side effects and treatment tolerance, with regular assessments of cancer progression. Researchers will measure outcomes such as dose-limiting toxicities, adverse events, progression-free survival, and overall survival. Quality of life will also be evaluated through questionnaires. The study may last up to several years, with monitoring continuing for safety and effectiveness throughout the treatment period and follow-up.

Researchers are studying new treatment options for people with high-risk non-muscle invasive bladder cancer HR NMIBC, including cases with carcinoma in situ CIS. HR NMIBC affects the lining of the bladder but has not spread to muscle or beyond. The study aims to learn if adding intismeran autogene V940 to the standard Bacillus Calmette-Guerin BCG immunotherapy can improve outcomes by helping the immune system attack the cancer more effectively. Participants are divided into groups receiving different treatments. One group Cohort A receives both intismeran autogene via intramuscular injection every 3 weeks for 9 doses and BCG instillations weekly in specific weeks over about 75 weeks. Another group receives only BCG following the same weekly schedule. A third group Cohort B receives intismeran autogene alone every 3 weeks for 9 doses. The study evaluates these treatments over several years. During the study, participants will have regular treatments and follow-up visits where researchers will monitor cancer progression, recurrence, and survival for up to approximately 5 years. Assessments include event-free survival, recurrence-free survival, overall survival, response rates, time to cystectomy, and safety outcomes such as adverse events and treatment discontinuation. The study is randomized and open-label, with detailed long-term monitoring planned.

Researchers are studying MK-1084, a targeted therapy, to treat advanced or metastatic non-squamous non-small cell lung cancer NSCLC with a specific KRAS G12C mutation. The study aims to evaluate the safety and tolerability of MK-1084 when combined with other treatments, and to see how many participants experience tumor shrinkage or disappearance. This trial is part of a larger master protocol and includes participants who have previously received certain cancer therapies. Participants will receive MK-1084 combined with either patritumab deruxtecan HER3-DXd or sacituzumab tirumotecan Sac-TMT until treatment is stopped due to side effects, adverse events, or investigator decision. MK-1084 is taken orally, while the other drugs are given by intravenous infusion. The arm combining MK-1084 with cetuximab was discontinued per protocol amendment. Throughout the study, participants will undergo assessments to monitor dose-limiting toxicities, adverse events, and treatment response for up to approximately 63 months. Researchers will also evaluate progression-free survival and drug concentration levels in the blood. Safety and treatment effects will be closely tracked, and participants may receive rescue medications to manage symptoms like nausea. The total study duration extends to 2032, with primary outcome evaluation by 2029.

Researchers are investigating new treatments for metastatic cervical cancer, which is cancer that has spread beyond the cervix, the lower part of the uterus. This study evaluates the safety and effectiveness of the antibody drug conjugate sacituzumab tirumotecan sac-TMT combined with pembrolizumab and bevacizumab. The goal is to find out if these treatments, given together or with some variations, help patients live longer or delay cancer progression compared to standard care. The study has two parts. In Part 1, participants receive sac-TMT, pembrolizumab, and bevacizumab together to assess safety. In Part 2, all participants first get standard induction treatment with pembrolizumab, paclitaxel, and cisplatin or carboplatin, possibly with bevacizumab. Those whose cancer does not worsen then enter maintenance treatment, where they are randomly assigned to receive either pembrolizumab alone or sac-TMT plus pembrolizumab, with optional bevacizumab. Participants are involved for up to about 20 months during maintenance treatment after up to 4 months of induction. The study monitors safety by tracking side effects and treatment discontinuations. Effectiveness is measured by progression-free survival and overall survival up to several years. Quality of life and physical functioning are also assessed through questionnaires. Treatments and evaluations occur through regular intravenous infusions and periodic monitoring visits.

Researchers are investigating new treatments for high-risk, early-stage breast cancer, specifically targeting two types triple-negative breast cancer TNBC and hormone receptor-low positiveHER2-negative breast cancer. These cancers are characterized by low or no HER2 protein and low hormone receptor presence. The study aims to evaluate if adding sacituzumab tirumotecan sac-TMT to pembrolizumab and chemotherapy can better reduce cancer cells in tumors and lymph nodes and improve the length of time patients live without cancer progression compared to pembrolizumab with chemotherapy alone. Participants in this trial receive one of two treatment plans. One group gets sacituzumab tirumotecan intravenously every two weeks plus pembrolizumab every three weeks for 12 weeks, followed by pembrolizumab with carboplatin and paclitaxel for another 12 weeks. After 3 to 6 weeks, surgery and optional radiation therapy take place, followed by pembrolizumab for about 28 weeks. Participants with remaining disease may receive additional treatments chosen by their doctors, including olaparib, capecitabine, doxorubicin, epirubicin, or cyclophosphamide. The other group receives chemotherapy drugs carboplatin and paclitaxel with pembrolizumab initially, then pembrolizumab with cyclophosphamide and doxorubicin or epirubicin, followed by surgery, optional radiation, and pembrolizumab for about 28 weeks, with similar additional options for residual disease. During the study, participants undergo core needle biopsies, receive intravenous infusions of study drugs, and have surgery and possible radiation therapy. Researchers assess outcomes such as the percentage of participants with no detectable cancer cells at surgery pathological complete response, event-free survival up to about 92 months, and overall survival up to nearly 10 years. Quality of life and side effects are monitored through questionnaires and adverse event tracking. The study lasts several years, with various assessments throughout treatment and follow-up periods to gather comprehensive data on treatment effects and safety.

Researchers are evaluating the safety, tolerability, and therapeutic effects of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first-line treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC positive for human papilloma virus 16 HPV16 and expressing the protein PD-L1 with a combined positive score of 1 or higher. This is an open-label, multi-site, Phase IIIII clinical trial consisting of two parts an initial safety run-in phase and a randomized phase. In the safety run-in phase Part A, patients receive BNT113 in combination with pembrolizumab to confirm safety and tolerability at selected dose levels. The randomized phase Part B compares BNT113 combined with pembrolizumab against pembrolizumab monotherapy. Treatments are given by intravenous injection or infusion and continue for up to 24 months. An optional pre-screening phase allows tumor samples to be tested for HPV16 DNA and PD-L1 expression before the main trial screening. Participants will be closely monitored throughout the study. Assessments include safety evaluations, tumor response, and survival outcomes such as overall survival and progression-free survival. Tumor tissue samples must be provided for testing. Researchers will measure treatment-emergent adverse events, response rates, duration of response, and disease control. The study may last up to 48 months, with ongoing safety and efficacy monitoring during and after treatment.

Researchers are evaluating the safety and effectiveness of rilvegostomig combined with platinum-based chemotherapy compared to pembrolizumab combined with platinum-based chemotherapy as a first treatment for patients with locally advanced or metastatic squamous non-small cell lung cancer mNSCLC whose tumors express programmed death-ligand 1 PD-L1. This Phase III global study focuses on patients with PD-L1 tumor cell expression of 1% or higher and aims to determine which treatment provides better overall and progression-free survival. Participants will be randomly assigned to one of two study groups one group will receive rilvegostomig plus carboplatin and either paclitaxel or nab-paclitaxel chemotherapy, while the other group will receive pembrolizumab plus the same chemotherapy options. Rilvegostomig and pembrolizumab are both given intravenously on Day 1 of each 21-day cycle, with chemotherapy given up to 4 cycles. Nab-paclitaxel may be administered on Days 1, 8, and 15 of each cycle. Treatment continues with rilvegostomig or pembrolizumab until disease progression or other criteria are met. During the study, participants will undergo regular assessments including imaging scans to measure tumor response, laboratory tests to monitor organ function, and patient questionnaires about physical function and quality of life. Researchers will track overall survival, progression-free survival, response rates, and duration of response for up to approximately 6 years. Safety and immune response to rilvegostomig will also be evaluated. Participants will be closely monitored throughout the treatment and follow-up periods.

Researchers are evaluating the efficacy and safety of volrustomig compared to observation in participants with unresected locally advanced head and neck squamous cell carcinoma LA-HNSCC who have not progressed after receiving definitive concurrent chemoradiotherapy cCRT. This phase III, randomized, open-label global study aims to assess whether volrustomig can improve outcomes in this patient population. Participants are randomly assigned to one of two groups those who receive volrustomig as sequential therapy, and those who undergo observation without additional treatment. The study compares these two approaches following prior curative concurrent chemoradiotherapy. The trial includes long-term follow-up to monitor patient outcomes. During the study, participants will be regularly assessed for progression-free survival, overall survival, physical functioning, and quality of life. Researchers will also monitor for the presence of anti-drug antibodies and adverse events related to volrustomig. Follow-up evaluations may continue for up to approximately eight years to fully understand the treatment impact and safety profile.

Researchers are evaluating the efficacy and safety of combining durvalumab and domvanalimab compared to durvalumab plus placebo in adults with locally advanced Stage III, unresectable non-small cell lung cancer NSCLC whose disease has not progressed after definitive platinum-based concurrent chemoradiotherapy cCRT. This Phase III, randomized, double-blind, placebo-controlled, international study aims to provide new insights into treatment options for this patient population. Participants will receive either durvalumab and domvanalimab or durvalumab plus placebo as intravenous infusions every four weeks, beginning on Day 1 and continuing for up to 12 months. The study includes two groups one receiving the combination of durvalumab and domvanalimab, and the other receiving durvalumab with a placebo. Both treatments are given through infusion to assess their effects on disease progression and safety. During the trial, participants will undergo regular assessments including monitoring progression-free survival for up to 8 years after randomization. Other measures include overall survival, response rates, duration of response, and various time-to-event outcomes related to disease progression and symptom deterioration. Researchers will also evaluate drug concentrations and immune responses approximately 12 weeks after the last dose. Participants can expect scheduled visits for infusions and evaluations as part of this long-term study.

Researchers are evaluating whether retatrutide and tirzepatide can prevent major adverse liver outcomes in adults with metabolic dysfunction-associated steatotic liver disease MASLD who are at high risk based on non-invasive tests. This Phase 3 randomized controlled trial aims to assess these treatments compared to placebo in about 4,500 adults over approximately 224 weeks. The study is sponsored by Eli Lilly and Company and focuses on liver disease progression and related health measures. Participants will be randomly assigned to receive retatrutide, tirzepatide, or placebo, all administered by subcutaneous injection. The trial includes two placebo groups corresponding to each experimental drug. After completing the main study, eligible participants may join a 2-year extension where all will receive either retatrutide or tirzepatide regardless of their initial assignment. During the study, participants may attend around 25 to 30 clinic visits for health monitoring, study procedures, and assessments of liver function and disease status. Researchers will measure the time to major adverse liver outcomes, changes in liver fibrosis scores, liver stiffness, liver fat content, liver enzyme levels, body weight, and cardiovascular events. Monitoring will continue from baseline through study completion, with detailed evaluations at multiple timepoints including week 104.