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Researchers are evaluating the safety and effectiveness of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM whose symptoms are not well controlled by SDT alone. This randomized, double-blind, placebo-controlled Phase 23 study includes multiple parts to assess different doses and durations of elenestinib treatment, including an open-label extension for participants finishing earlier phases. The study also enrolls participants who have previously received an approved selective KIT inhibitor and includes pharmacokinetic groups. Participants receive oral elenestinib or placebo once daily alongside SDT, which is personalized based on individual symptom management needs. Part 1 focuses on short-term treatment lasting up to 12 weeks, while Part 2 extends treatment to approximately 48 weeks. Part 3 and other parts allow treatment for up to about 5 years. The study monitors participants through these phases to evaluate how elenestinib affects symptoms, disease markers, and safety over time. During the study, participants undergo regular assessments of symptoms using the ISM-Symptom Assessment Form ISM-SAF, laboratory tests including serum tryptase and KIT D816V allele levels, bone marrow evaluations, and quality of life measures. Researchers track adverse events and changes in disease-related factors at various points up to 5 years. This thorough monitoring helps measure treatment effects and safety over both short and long-term periods, with total participation lasting several years depending on the study part.

Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Researchers are conducting a Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of rilzabrutinib in adults with active Immunoglobulin G4-related disease IgG4-RD. The study aims to measure the time to the first adjudicated disease flare and assess other important outcomes such as flare-free rates, disease activity control, glucocorticoid use, and safety parameters including adverse events, laboratory tests, and electrocardiograms ECG. Participants will be assigned to one of two groups one receiving rilzabrutinib tablets and the other receiving placebo tablets, both administered orally. The treatment period lasts 52 weeks in a double-blind manner, preceded by a 4 to 6 week screening period. After treatment, there is a 2-week follow-up, with an optional open-label extension lasting up to 108 weeks. The study includes a total of 16 visits during the main period and up to 9 additional visits during the optional extension. During their participation, adults diagnosed with IgG4-RD will undergo repeated imaging procedures such as CT, MRI, PET, or ultrasound to assess disease status. Researchers will monitor disease flares, remission status, glucocorticoid dosage, clinical activity scores, laboratory values, vital signs, and ECG results. Safety monitoring continues up to week 160 to capture treatment-emergent adverse events. Overall, participation lasts up to 60 weeks, with possible extension for those continuing in the optional phase.

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 investigating new treatments for advanced renal cell carcinoma RCC that has returned after prior therapy. The study aims to find out if the combination of belzutifan and zanzalintinib can help people with recurrent advanced RCC live longer without their cancer worsening compared to the drug cabozantinib. This is a phase 3 randomized trial evaluating these treatments in participants who have experienced recurrence during or after prior anti-PD-1L1 therapy. Participants are randomly assigned to receive either belzutifan plus zanzalintinib taken orally once daily or cabozantinib taken orally once daily. They continue their assigned treatment until certain reasons require stopping the study intervention. The study compares the effects of these treatments on cancer progression and survival among people with advanced RCC who have had disease recurrence after adjuvant therapy. During the study, participants will be regularly monitored for progression-free survival and overall survival for up to about 73 months. Researchers will also assess tumor response, duration of response, adverse events, and quality of life using questionnaires over approximately 25 months. The study involves ongoing evaluations to understand how these treatments affect symptoms, functioning, and overall health during long-term follow-up.

Researchers are evaluating if combining the medicines calderasib and subcutaneous pembrolizumab can more effectively treat people with non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The study aims to find out whether patients receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a Phase 3 clinical trial focusing on first-line treatment for advanced or metastatic nonsquamous NSCLC. Participants are assigned to one of two groups. One group receives subcutaneous pembrolizumab plus berahyaluronidase alfa every 6 weeks for up to 18 cycles about 2 years along with oral calderasib until treatment discontinuation criteria are met. The other group receives the same pembrolizumab and berahyaluronidase alfa regimen plus chemotherapy with pemetrexed and either carboplatin or cisplatin infusions during the early cycles. Treatment continues based on individual response and tolerability. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess progression-free survival, overall survival, response rates, and quality of life using questionnaires and symptom scores over several years. Safety will be monitored through adverse event reporting. The trial lasts up to about 7 years with ongoing evaluation of health outcomes and side effects to understand the impact of these treatment combinations.

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.