NTRK Fusion

Researchers are studying the use of Ensartinib in people with advanced ALK-positive non-small cell lung cancer (NSCLC). The study aims to evaluate how well Ensartinib works and its safety, as well as to understand how the drug moves through the body and how resistance to it may develop. This research is observational and focuses on patients whose cancer has progressed after previous ALK-TKI treatments. Participants will take Ensartinib orally at a dose of 225 mg once daily. Treatment continues until the disease worsens or if certain conditions like patient choice, side effects, or pregnancy occur. When the disease progresses, patients enter a follow-up period to monitor survival until death, withdrawal, or study end. Blood samples will be collected three times: before starting treatment, after 8 weeks, and at disease progression, to analyze genetic material and drug levels. During the study, participants will undergo routine blood tests and assessments of their cancer status. Researchers will track progression-free survival over 36 months as the main outcome. They will also measure response rates, overall survival up to 48 months, and record any adverse events. This comprehensive monitoring helps evaluate how patients respond to Ensartinib and understand the safety of treatment over time.

Researchers are evaluating the safety, pharmacokinetics, and preliminary effectiveness of NST-628, an oral drug targeting the MAPK pathway, in adults with advanced solid tumors that have specific genetic mutations and have exhausted standard treatments. This Phase 1, open-label, multi-center study includes patients with tumors dependent on the MAPK pathway, such as melanoma and glioma, aiming to find a suitable dose and observe tumor responses. The study has two parts: Part A involves dose escalation where increasing doses of NST-628 are given once daily in 28-day cycles to determine the maximum tolerated dose and the recommended dose for expansion. Part B involves dose expansion with several cohorts of patients harboring specific MAPK pathway mutations receiving the recommended dose to further assess safety and tumor response. Dose adjustments may be made based on observed effects. Participants will undergo regular assessments including safety evaluations, tumor response measurements using standardized criteria, and pharmacokinetic analyses throughout the study, which lasts about one year on average for primary outcomes and up to two years for survival monitoring. Tumor tissue samples are required, and patients will be followed until the last visit of the final participant. Safety, tumor response, progression-free survival, overall survival, and drug behavior in the body are key outcomes measured.

Researchers are evaluating the safety, effectiveness, and tolerability of APL-101 in treating various advanced solid tumors, especially non-small cell lung cancer (NSCLC) with MET Exon 14 skipping mutations, MET amplification, MET fusion, and tumors with overexpression of HGF and MET. This Phase 2 study follows a completed Phase 1 enrollment and focuses on patients with unresectable or metastatic cancers who have varying prior treatment histories and genetic tumor profiles. The study also examines APL-101 as an add-on therapy with EGFR inhibitors for NSCLC patients who developed resistance due to MET amplification. Participants receive APL-101 as oral capsules taken twice daily. The study includes multiple cohorts based on tumor type, prior treatment, and genetic characteristics, such as treatment-naive NSCLC patients with MET mutations, those previously treated with or without MET inhibitors, and patients with other solid tumors harboring specific MET alterations. One cohort also receives APL-101 combined with standard EGFR inhibitors. The treatment continues in cycles of 28 days, with ongoing assessment of response and safety. Throughout the study, participants undergo regular evaluations including imaging to identify measurable tumor lesions, laboratory tests, and functional assessments such as ECOG performance status or Karnofsky Performance Status for CNS tumors. Researchers measure outcomes like objective response rate, duration of response, time to progression, progression-free survival, and overall survival over periods extending up to three years. Safety monitoring includes organ function tests and tracking adverse effects. The total duration varies by participant based on treatment response and progression.

Researchers are studying Canadian cancer patients who have rare genetic changes in their tumors, such as alterations in genes like ALK, EGFR, ROS1, BRAF, and KRAS G12C. These rare molecular alterations can affect how the cancer responds to certain targeted drugs called tyrosine kinase inhibitors (TKIs). The study aims to better understand the natural history of these cancers and compare treatment outcomes, including side effects and patient-reported experiences, across different therapies. The study observes cancer patients who have received or are currently receiving TKIs or other targeted therapies. It includes three groups: living patients with confirmed rare molecular alterations, deceased patients with such alterations, and a comparator group of cancer patients without these rare changes. Patient-reported outcomes are collected through surveys at baseline and every three months, especially when treatments change. Participants provide molecular testing reports and complete quality of life questionnaires regularly for up to 10 years. Researchers track progression-free survival or overall survival, the development of brain metastases, and economic impacts related to treatment. The study collects data from medical records and patient surveys to understand treatment patterns, effectiveness, and quality of life in the real-world Canadian context.

Researchers are evaluating a cancer peptide vaccine to prevent or delay acquired resistance in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) who are currently receiving ALK targeted therapy. This pilot study focuses on assessing the safety of the vaccine in these patients with stage IV NSCLC or recurrent NSCLC not suitable for definitive multimodality therapy. The study is sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and includes patients with documented ALK rearrangement and stable disease on ALK inhibitors for at least 4 months. All participants will receive the peptide vaccine intervention during the study. The vaccine is a biological agent designed to target specific ALK acquired resistance alterations that the patients do not currently have. The study does not include a placebo or comparison group; instead, it monitors the treatment-related adverse events and vaccine-specific immune responses over up to two years. The trial spans phases 1 and 2 and involves ongoing treatment with approved ALK inhibitors such as crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib. Participants will be closely monitored for safety and immune reactions related to the vaccine. Researchers will collect data on treatment-related side effects and immune responses for up to two years after vaccination. Eligibility evaluations include confirming ALK rearrangement by various testing methods and stable disease status. Patients with certain other malignancies, recent chemotherapy or immunotherapy, systemic immune suppression, or symptomatic central nervous system metastases are excluded. The study aims to provide important information on vaccine safety and immune effects in this patient population over the course of the trial.

Researchers are evaluating a new approach for women with recurrent ovarian cancer using a novel mRNA-based test called Signal Transduction Activation (STA) analysis. This technique identifies the main active signal transduction pathway (STP) driving tumor growth to guide targeted therapy with existing drugs that have manageable side effects. The goal is to improve progression-free survival and maintain quality of life by matching therapy to each patient's tumor biology. The study includes women with platinum-resistant recurrent ovarian cancer or those who are not yet eligible or who decline standard chemotherapy. After a biopsy of the recurrent tumor, STA analysis determines the dominant pathway. Patients with active estrogen receptor, androgen receptor, phosphoinositide 3-kinase, or Hedgehog pathways will receive corresponding targeted drugs such as Letrozole, Bicalutamide, Everolimus, or Itraconazole daily until disease progression. Treatment decisions are reviewed by a multidisciplinary tumor board. Participants will be monitored regularly with imaging every 12 weeks to assess tumor response and progression according to RECIST 1.1 criteria. Researchers will collect data on progression-free survival comparing current therapy to prior treatment, side effects, quality of life, and overall survival for up to 36 months. Additional evaluations include changes in pathway activity scores and health economics. The study runs up to 36 months with ongoing safety and treatment effect monitoring.

Researchers are evaluating ICP-723 in patients with advanced solid tumors or primary central nervous system (CNS) tumors that have NTRK gene fusions. This open-label, multi-center Phase 2 basket clinical trial aims to assess ICP-723's effects in people who have not previously received NTRK inhibitor treatment. The study focuses on patients with measurable tumors and good performance status to better understand treatment responses and safety. Participants receive ICP-723 tablets orally once a day, with each treatment cycle lasting 28 days. This is a non-randomized study without a placebo group, and all participants are given the study drug. The trial spans an average of four years during which researchers monitor tumor responses and other health outcomes. Throughout the study, participants undergo regular evaluations including tumor measurements using RECIST, RANO, or INRC criteria, depending on tumor type. Safety is closely monitored by assessing adverse events and heart function. Researchers also measure drug levels in the blood and track survival and disease progression. The total study duration allows for long-term follow-up of effectiveness and side effects.

Researchers are studying the safety, how the body processes, and the effects of TAS0953/HM06, a selective RET inhibitor, in adults with advanced solid tumors that have specific RET gene abnormalities. The study is conducted in two phases: Phase 1 focuses on finding the highest dose patients can tolerate and the best dose for Phase 2, while Phase 2 evaluates how well this dose works. This research is sponsored by Taiho Pharmaceutical Co., Ltd. and spans both Phase 1 and Phase 2 clinical trial stages. In the first phase, participants receive TAS0953/HM06 orally, starting at 20 mg twice daily, with continuous daily dosing in 21-day cycles. Dose escalation and expansion continue until the appropriate Phase 2 dose is determined. In the second phase, participants take the recommended dose twice daily in similar 21-day cycles. Treatment is given continuously during both phases to assess safety and efficacy across different patient groups, including those with prior exposure to similar inhibitors and those without. Throughout the study, participants undergo regular assessments such as physical exams, blood tests, and imaging scans to monitor tumor response and drug levels. In Phase 1, dose tolerance and pharmacokinetics are evaluated at the end of the first cycle and over approximately 10 months. Phase 2 participants are monitored for tumor response every 6 weeks for 6 months, then every 9 weeks during treatment, with follow-up extending up to two years. Safety is closely tracked through adverse event reporting and heart monitoring, with additional evaluations after treatment ends.