Harderwijk

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 conducting a Phase 3 study to compare two front-line treatments for adults with nonsquamous non-small cell lung cancer (NSCLC) that is stage IV or advanced stage IIIB/C. The study focuses on patients whose tumors have a KRAS p.G12C mutation and are negative for PD-L1 expression. The main goal is to evaluate how each treatment affects progression-free survival and overall survival over about 2.5 years. Participants will be randomly assigned to receive either sotorasib combined with platinum doublet chemotherapy or pembrolizumab combined with platinum doublet chemotherapy. Sotorasib is given orally, while pembrolizumab is given intravenously. Both groups will receive the combination therapies as their initial treatment for advanced NSCLC. During the study, participants will be monitored regularly to assess treatment effects and safety. Researchers will track how long patients live without the cancer worsening and overall survival over approximately 2.5 years. The study includes evaluations to determine eligibility and ongoing assessments to monitor health and treatment response throughout the trial period.

Researchers are evaluating the safety and effectiveness of divarasib combined with pembrolizumab compared to pembrolizumab with pemetrexed and either carboplatin or cisplatin. The study focuses on adults with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation. This is a Phase III trial aiming to improve first-line treatment options for these patients. Participants will receive one of two treatment combinations. One group will take divarasib orally once daily along with pembrolizumab given through an intravenous infusion every three weeks. The other group will receive pembrolizumab with pemetrexed and either carboplatin or cisplatin, all administered by intravenous infusion every three weeks. Treatment schedules and dosages are carefully monitored during the study. Throughout the study, participants will be regularly assessed for progression-free survival and overall survival, with follow-up lasting up to approximately five years. Researchers will perform various evaluations including tumor measurements and safety monitoring. This long-term observation helps to understand the treatments' effects and safety over time, supporting informed decisions for future lung cancer therapies.

Researchers are evaluating the safety and effectiveness of calderasib combined with pembrolizumab as a first treatment in adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation and a PD-L1 tumor proportion score of 50% or higher. This Phase 3 trial aims to test if the combination of calderasib and pembrolizumab improves progression-free survival and overall survival compared to pembrolizumab with a placebo. Participants receive oral calderasib tablets or placebo along with pembrolizumab given by intravenous infusion. The study compares these two treatment groups to see which provides better outcomes. Treatments continue during the study, and there are no additional interventions described beyond these drugs. During the trial, participants undergo regular assessments including scans and tests to monitor their cancer's progression and overall health. The main outcomes measured are progression-free survival for up to about 42 months and overall survival for up to about 56 months. Safety is monitored throughout, and participants are followed for several years to evaluate long-term effects of the treatments.

Researchers are evaluating the effectiveness of adding LY3537982 (olomorasib) to standard anti-cancer drugs compared to standard treatment alone in participants with untreated advanced non-small cell lung cancer (NSCLC) that has a specific KRAS G12C gene mutation. This pivotal Phase 3 trial includes participants with locally advanced or metastatic NSCLC and considers their programmed death-ligand 1 (PD-L1) expression levels. The study includes multiple parts: Dose Optimization, Part A, and Part B are randomized, while Safety Lead-In for Part B and Part C are non-randomized. Treatments being assessed include LY3537982 taken orally, pembrolizumab administered intravenously, and standard chemotherapy drugs such as cisplatin, carboplatin, and pemetrexed given intravenously. Participants receive these treatments according to their assigned groups based on their PD-L1 expression and tumor histology. Participants will be monitored with regular assessments including measuring disease progression, safety evaluations, and treatment emergent adverse events for up to approximately one year, with overall study participation potentially lasting up to three years depending on individual response and health status. Outcome measures focus on progression-free survival and safety, capturing any adverse events from the start of treatment until disease progression or death.

Researchers are evaluating the safety and effectiveness of telisotuzumab vedotin compared to docetaxel in adults with previously treated non-squamous non-small cell lung cancer (NSCLC) that overexpresses c-Met. This phase 3 study focuses on participants with advanced or metastatic NSCLC who have specific genetic markers and have progressed after prior therapies. The study aims to assess changes in disease activity and adverse events over time. Participants will be randomly assigned to receive either intravenous telisotuzumab vedotin every two weeks or intravenous docetaxel every three weeks. Treatment continues until predefined discontinuation criteria are met. Those who benefit from the study treatment may have the option to continue receiving it through an extension or rollover study. Approximately 698 adults will be enrolled worldwide at about 330 sites. During the study, participants will attend regular hospital or clinic visits for medical assessments, blood tests, side effect monitoring, and questionnaires. Researchers will measure progression-free survival and overall survival for up to approximately 39 months. The study includes careful safety monitoring and evaluates the impact of treatment on disease progression and patient well-being.

Researchers are comparing the effectiveness of two treatments for participants with stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC) who have PD-L1 expression of 1% or higher. This phase 3, randomized, open-label study focuses on first-line treatment options and aims to evaluate overall survival over up to five years for participants with PD-L1 levels between 1% and 49%. The trial involves participants with measurable disease and good performance status who have not received prior systemic therapy for advanced disease. The study compares a combination of Nivolumab and Relatlimab plus chemotherapy against Pembrolizumab plus chemotherapy. Chemotherapy drugs include Carboplatin, Pemetrexed, and Cisplatin, administered at specified doses on scheduled days. Participants are randomly assigned to receive either the Nivolumab and Relatlimab combination with chemotherapy or Pembrolizumab with chemotherapy as their initial treatment. Treatment schedules and doses are defined but not detailed here. Participants will be closely monitored throughout the study, which may last up to five years. Researchers will assess overall survival as the primary outcome, along with regular imaging tests like CT or MRI to measure disease status. Eligibility screening includes assessing PD-L1 levels, performance status, and other health factors. Safety monitoring and follow-up will continue to evaluate treatment effects and participant well-being during and after treatment.

Researchers are investigating the safety and effectiveness of Dato-DXd combined with osimertinib or alone compared to platinum-based doublet chemotherapy in treating adults with epidermal growth factor receptor-mutated (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC). This Phase III, open-label study includes participants whose disease has worsened despite prior osimertinib treatment. The goal is to evaluate progression-free survival (PFS) over up to 2.5 years. Participants are randomly assigned to one of three groups: Dato-DXd plus osimertinib, Dato-DXd alone, or platinum-based doublet chemotherapy. Dato-DXd and chemotherapy drugs (pemetrexed, carboplatin, or cisplatin) are given by intravenous infusion, while osimertinib is taken orally. Treatment continues until the cancer progresses based on imaging, unacceptable side effects occur, or other reasons require stopping treatment. After stopping the study drugs, participants will have an end-of-treatment visit within 35 days and safety follow-up about one month later. During the trial, researchers will monitor participants with radiological scans and assess progression-free survival. Safety evaluations will continue after treatment ends to detect any side effects. The study includes adults aged 18 to 130 years with good performance status and adequate organ function who have progressed on prior osimertinib therapy. The total study duration includes treatment and follow-up periods to ensure thorough assessment of treatment effects and safety.

Patients in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) with non-metastatic colon cancer that gave consent for additional blood withdrawals are enrolled in the observational PLCRC-MEDOCC substudy. In this study, blood is collected before surgery, after surgery and during follow-up. Within PLCRC-MEDOCC, patients with stage II colon cancer that are not considered to have an indication for adjuvant chemotherapy, can be included in the MEDOCC-CrEATE subcohort under the condition that they gave informed consent in PLCRC for biobanking of tissue and for future studies (Trial within Cohorts design). Patients included in MEDOCC-CrEATE will be randomized 1:1 to the (A) ctDNA-based treatment group versus (B) the standard of care group. A total of 1320 patients will be randomized. Patients randomized to the ctDNA-based treatment group will have their post-surgery samples analysed directly after informed consent for MEDOCC-CrEATE. All patients with detectable ctDNA will be offered adjuvant chemotherapy (3 months CAPOX). Patients with undetectable ctDNA will receive routine follow-up at the surgical department. The aim of this Trial within Cohorts study is to investigate how many patients with detectable ctDNA after surgery start with adjuvant chemotherapy.

Researchers are evaluating chemotherapy dosing strategies for older patients aged 70 years and above who have metastatic colorectal cancer and are candidates for palliative chemotherapy. This phase III, open-label, randomized controlled trial aims to compare upfront dose-reduced chemotherapy with standard full-dose chemotherapy to see if the reduced dose is not worse in terms of progression-free survival (PFS). The study also examines secondary outcomes including severe toxicity, quality of life, physical function, overall survival, treatment cycles, dose reductions, hospital admissions, cumulative dosage, and cost-effectiveness. Participants are classified based on their risk of chemotherapy toxicity using the Geriatric 8 (G8) questionnaire. Those at low risk are randomized to receive either full-dose or 25% dose-reduced doublet chemotherapy (a fluoropyrimidine combined with oxaliplatin). Patients at high risk receive either full-dose or dose-reduced monotherapy with a fluoropyrimidine. Targeted treatments like bevacizumab or EGFR inhibitors may be added. Dose adjustments are made for moderate kidney impairment. Treatments are given on schedules involving oral and intravenous chemotherapy drugs administered every 2 to 3 weeks. During the study, participants undergo assessments including clinical evaluations, laboratory tests to monitor blood counts and organ function, and questionnaires for quality of life and physical functioning. Progression-free survival is tracked for at least one year after randomization. Researchers closely monitor treatment toxicity, hospitalizations, dose modifications, and survival. The total planned enrollment is 587 patients, with follow-up for safety and effectiveness throughout the treatment period.