Haifa

Researchers are evaluating new treatments for advanced renal cell carcinoma RCC, a type of kidney cancer. This study compares the effects of combining two targeted therapies, belzutifan and zanzalintinib, against belzutifan with a placebo. The goal is to see if the combination can help people live longer and prevent the cancer from getting worse after other treatments have failed. Participants will take 120 mg of belzutifan orally and either 60 mg of zanzalintinib or a matching placebo once daily for about 24 months. The study is randomized and double-blind, meaning neither participants nor researchers know who receives the active combination or placebo. Two groups are compared belzutifan plus zanzalintinib and belzutifan plus placebo. During the study, participants will be monitored for progression-free survival and overall survival, with assessments up to around 30 to 50 months. Researchers will also evaluate tumor response, duration of response, quality of life, and side effects. Safety and tolerability will be tracked throughout treatment and follow-up periods. The study is sponsored by Merck Sharp & Dohme LLC and aims to provide important information on treating advanced RCC.

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 investigating new treatments for extensive-stage small cell lung cancer ES-SCLC, a type of lung cancer that has spread widely within the lungs or to other parts of the body. This study evaluates the combination of two study medicines, gocatamig and I-DXd ifinatamab deruxtecan, with or without standard chemotherapy and immunotherapy. The research aims to understand the safety and tolerance of these combinations and whether they can shrink or eliminate tumors in people with ES-SCLC. Participants are assigned to one of several treatment groups. Some receive gocatamig and I-DXd during maintenance after completing standard chemotherapy and immunotherapy, while others receive these study medicines during both induction and maintenance phases. Additional groups receive gocatamig and I-DXd followed by gocatamig and atezolizumab, or standard treatment with carboplatin, etoposide, and atezolizumab followed by atezolizumab maintenance. Treatments are given intravenously and continue until disease progression or other study-specified criteria. During the study, participants will have regular assessments to monitor safety, side effects, and treatment response, including scans to measure tumor size and laboratory tests to evaluate drug levels and immune response. The study will track adverse events, treatment tolerability, and cancer control over up to approximately 58 months. Participants health status and responses to the treatments will be closely observed throughout this period, with periodic evaluations to understand long-term effects and outcomes.

Researchers are studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

This research investigates treatments for metastatic castration-resistant prostate cancer mCRPC focusing on a drug called ifinatamab deruxtecan I-DXd. The study aims to assess the safety, how well participants tolerate the treatments, and appropriate dosing levels of I-DXd alone or combined with other therapies. Researchers will also monitor participants prostate specific antigen PSA levels during treatment to understand its effects. Participants are assigned to one of several treatment groups. One group receives docetaxel every three weeks for up to 10 cycles. Other groups receive I-DXd alone or combined with either opevesostat or androgen receptor pathway inhibitors such as abiraterone acetate or enzalutamide. I-DXd is given every three weeks until unacceptable side effects, disease progression, death, or withdrawal, while the other drugs continue until specific discontinuation criteria are met. Premedication is required before each I-DXd dose to prevent nausea and vomiting. Throughout the study, participants undergo various assessments including monitoring of dose-limiting toxicities, adverse events, and PSA response rates. Researchers also track objective response rates, progression-free survival, overall survival, and other clinical outcomes over up to approximately 54 months. The study involves regular evaluations to assess safety and treatment effects until study completion.

Researchers are evaluating MK-1045, an immunotherapy, in people with two types of non-Hodgkin lymphoma NHL follicular lymphoma FL, which grows slowly, and diffuse large B-cell lymphoma DLBCL, which grows more quickly. NHL is a cancer of the lymphatic system causing swollen lymph nodes. This study aims to assess the safety and tolerability of MK-1045 and to see if it can shrink or eliminate these lymphomas. Participants are randomly assigned to one of four groups receiving different doses or methods of MK-1045 administration. Dosages A, B, and D are given by intravenous IV infusion, while Dosage C is given by subcutaneous SC injection. Treatment lasts for up to approximately one year or until participants stop treatment for any reason. During the study, participants will be monitored for adverse events and treatment side effects, with measurements including tumor response using specific criteria. Blood levels of MK-1045 will also be tracked. The study involves regular visits for infusions and assessments. Participant safety and treatment effects will be followed for up to about 49 months in total.

Researchers are evaluating the safety and tolerability of MK-4716, a drug being studied alone or combined with other treatments in people with certain advanced or metastatic solid tumors that have KRAS alterations. This phase 1, open-label study includes participants with locally advanced unresectable or metastatic solid tumors or metastatic non-small cell lung cancer, focusing on those with measurable disease and specific prior treatment histories. Participants receive MK-4716 at varying dose levels and schedules as monotherapy or combined with Pembrolizumab or Cetuximab. MK-4716 is given orally, while Pembrolizumab and Cetuximab are administered intravenously. The study uses a parallel design with several experimental arms to assess different combinations and dosing. During the study, participants are monitored for dose-limiting toxicities up to about 28 days and for adverse events up to approximately four years. Researchers measure drug concentrations in the blood at designated timepoints, pharmacokinetics, and overall safety. Participants undergo regular evaluations to assess side effects, treatment tolerability, and disease status throughout the study period, which lasts until study completion in December 2030.

Researchers are studying MK-8294, a targeted therapy designed to treat advanced solid tumors, including various squamous cell carcinomas and breast, endometrial, and bladder cancers. This phase 1 open-label study aims to evaluate the safety of MK-8294, determine if patients can tolerate it, and identify the highest dose level that participants can handle. The study enrolls adults with confirmed advanced or metastatic solid tumors who have limited or no standard treatment options. Participants will receive MK-8294 as a monotherapy in escalating intravenous doses starting from 30 micrograms up to 70 milligrams, given on Days 1, 8, and 15 of each 21-day cycle. There is no maximum number of treatment cycles, and participants will continue treatment until criteria for stopping are met. Some participants may also undergo optional PET imaging using a CD8 tracer to help assess treatment effects. Throughout the study, participants will be carefully monitored for side effects and treatment tolerance, with dose-limiting toxicities tracked up to about 35 days. Researchers will also observe adverse events and reasons for discontinuing treatment for up to approximately two years. Blood samples will be collected during each cycle to measure MK-8294 levels and immune responses. The overall study duration may last up to two years to fully assess safety and treatment effects.

Researchers are investigating new treatment options for breast cancer that is hormone receptor-positive HR and human epidermal growth factor receptor 2-negative HER2-, specifically for cases that are unresectable locally advanced or metastatic. This type of breast cancer involves cancer cells that depend on hormones like estrogen or progesterone and have low HER2 protein levels. The study focuses on comparing the effects of patritumab deruxtecan against chemotherapy or trastuzumab deruxtecan in patients whose cancer has progressed despite prior treatments. Participants receive either patritumab deruxtecan through intravenous infusions every three weeks for about 13 months or a treatment chosen by their physician, which may include various chemotherapy drugs or trastuzumab deruxtecan, administered according to specific schedules for up to 13 months. The study is randomized and open-label, meaning participants are randomly assigned to one of the treatment groups, and both the patients and researchers know which treatment is given. Throughout the study, participants undergo regular assessments to monitor cancer progression and overall survival for up to approximately 85 months. Researchers evaluate tumor response, duration of response, and changes in quality of life using standardized questionnaires. Safety is carefully monitored by recording adverse events and treatment discontinuations. The goal is to understand if patritumab deruxtecan can improve outcomes compared to current treatment options.

Researchers are exploring new treatments for women with relapsed high-grade serous ovarian cancer, which is a fast-growing cancer starting in ovarian cells, the lining of the belly, or fallopian tubes. The study evaluates raludotatug deruxtecan R-DXd, a type of antibody drug conjugate, combined with other therapies, to understand safety, tolerability, and cancer response. This includes women with platinum-sensitive and platinum-resistant recurrent ovarian cancer who have had prior treatments. The study has two parts Part 1 involves gradually increasing doses of R-DXd combined with chemotherapy drugs like carboplatin, paclitaxel, bevacizumab, or pembrolizumab to find a recommended dose. Part 2 uses this recommended dose to further assess treatment effects. Participants receive intravenous infusions every three weeks, with chemotherapy cycles lasting up to about four months and pembrolizumab up to two years. The combinations vary depending on cancer sensitivity and treatment history. Participants undergo regular treatment visits where cancer response and side effects are monitored. Tumor tissue samples are collected before treatment. Researchers track adverse events, dose-limiting toxicities, and how long the cancer responds to treatment. The study lasts up to approximately three years, allowing for long-term safety and effectiveness assessments, with ongoing evaluation of participants health throughout the trial.