Atlanta

Researchers are investigating CGT9486, also known as bezuclastinib, in an open-label Phase 2 study for patients with Advanced Systemic Mastocytosis AdvSM. This includes those diagnosed with Aggressive Systemic Mastocytosis ASM, Systemic Mastocytosis with an Associated Hematologic Neoplasm SM-AHN, and Mast Cell Leukemia MCL. The study aims to evaluate the safety, effectiveness, pharmacokinetics, and pharmacodynamics of bezuclastinib in this patient population. Participants will receive bezuclastinib tablets orally, taken continuously in 28-day cycles. The study is divided into two parts Part I focuses on identifying effective and tolerable dosing exposures over 18 months, while Part II evaluates the drugs efficacy by measuring objective response rates and confirming the exposure-response relationship, also over 18 months. Additional assessments include effects on mutation allele burden, serum tryptase levels, histopathologic changes, spleen and liver volume, and safety monitoring. During the study, participants will undergo various clinical evaluations, including laboratory tests, imaging to monitor organ size changes, and assessments of disease response and progression. Researchers will track adverse events and pharmacokinetic profiles throughout the 18 months. The study involves continuous monitoring of participants to understand the treatments impact on survival and disease progression over this period.

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 studying how the duration of oxaliplatin infusion affects nerve damage in patients with gastrointestinal cancers. This phase II trial compares giving oxaliplatin over 2 hours versus 6 hours to see if a longer infusion can reduce or delay nerve damage, which may allow patients to stay on standard chemotherapy doses longer without delays. The European Organization for Research and Treatment of Cancers patient-reported neuropathy scale CIPN-20 is used to measure nerve damage severity. Participants are randomly assigned to one of two groups one receives oxaliplatin and leucovorin intravenously over 2 hours along with fluorouracil given in two doses a quick low dose and a continuous higher dose on day 1 the other receives oxaliplatin over 6 hours with leucovorin and fluorouracil as in the first group. Treatments are repeated every 14 days unless disease progresses or side effects are unacceptable. After treatment, patients are followed up at 1, 3, 6, 12, and 18 months. Throughout the study, patients undergo evaluations including measurements of nerve damage using the CIPN-20 scale, pharmacokinetic tests to assess drug concentration and clearance, tumor size monitoring, and records of therapy duration, dose adjustments, and treatment delays. These assessments help researchers understand how infusion time affects nerve damage severity and overall treatment delivery. The total participation duration includes the treatment period and up to 18 months of follow-up.

Researchers are evaluating the long-term safety and tolerability of LB-102 in adults with stable schizophrenia who have had inadequate responses, side effects, or issues with their current antipsychotic medications, or who have completed prior LB-102 studies. This Phase 3, open-label, multicenter trial focuses on patients aged 18 to 65 years with stable disease and aims to provide extended monitoring of this treatment. Participants will receive LB-102 with flexible dosing ranging from 50 mg to 100 mg. This single-group study involves administering the drug openly over 52 weeks to assess how well patients tolerate it and to monitor safety during this period. Throughout the study, participants will undergo evaluations including monitoring adverse events and treatment-emergent events. Effectiveness will be assessed using the Positive and Negative Syndrome Scale PANSS. The study lasts up to 52 weeks, during which safety and tolerability are carefully observed and recorded.

Researchers are evaluating the safety and effectiveness of tenapanor in adults with Chronic Idiopathic Constipation CIC. This study is a 26-week, multi-center, randomized, double-blind, placebo-controlled trial followed by a 4-week treatment-free safety follow-up period. It aims to compare three different doses of tenapanor with a placebo taken twice daily to assess their impact on constipation symptoms. The study includes a 2-week screening period to confirm eligibility, followed by a 26-week randomized treatment period where patients receive either 5 mg, 25 mg, or 50 mg of tenapanor twice daily, or a matching placebo. Patients record their constipation symptoms daily in an electronic diary. After the treatment period, there is a 4-week safety follow-up without treatment to monitor any adverse effects. Participants will have regular visits every 2 to 6 weeks for safety checks including medical assessments, vital signs, ECG, and lab tests. Their symptom diaries will be reviewed throughout the study. The main outcome measured is the durable complete spontaneous bowel movements response at 12 weeks. Secondary outcomes include changes in bowel movement frequency, stool consistency, and straining. The total study duration is approximately 32 weeks including all phases.

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 MDNA11, a long-acting beta-only recombinant interleukin-2 designed to activate immune cells that kill cancer while minimizing activation of immunosuppressive cells. This Phase 12 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with the checkpoint inhibitor pembrolizumab in patients with advanced solid tumors. The study is conducted at multiple sites with regulatory and ethical approvals and includes about 115 patients. The trial has several parts dose escalation and expansion for MDNA11 monotherapy and for its combination with pembrolizumab. MDNA11 is given intravenously every two weeks with doses adjusted to find the recommended dose for expansion. Tumor assessments using CT or MRI scans happen every 8 weeks to monitor response until disease progression or other study-end criteria occur. Treatment may continue beyond progression under certain conditions. Participants undergo evaluations including tumor imaging, laboratory tests, and safety monitoring over up to 24 months. Researchers measure recommended dose levels, treatment-related adverse events, pharmacokinetics, immune response, and anti-tumor activity such as response rates and progression-free survival. Patients can withdraw anytime, and safety follow-up continues to understand MDNA11s effects alone and with pembrolizumab.

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.

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 evaluating the safety, efficacy, and optimal dosing of a combination of two investigational treatments, BNT323 trastuzumab pamirtecan and BNT327 pumitamig, in people with advanced breast cancer. This includes those with hormone receptor-positive or -negative, HER2-positive, HER2-low, HER2-ultralow, HER2-null breast cancer, or triple-negative breast cancer. The study is a Phase III multi-site, open-label trial with a focus on advanced breast cancer treatment options. The study has two parts. Part 1 involves dose escalation of BNT323 combined with BNT327 to determine the recommended Phase 2 dose using six different dose levels. Part 2, which begins after Part 1 completion, includes dose optimization and exploratory cohorts. Cohort 1 in Part 2 uses randomization into four treatment arms, including combination therapy at different doses and monotherapies of either BNT323 or BNT327. Other cohorts receive the recommended dose without randomization. Participants will undergo assessments including tumor scans and cardiac function tests, with monitoring for side effects and tumor response up to 36 months. Researchers will track dose-limiting toxicities and treatment-emergent adverse events during early treatment cycles and monitor objective response rates and disease control over time. Safety and efficacy data will be collected through scheduled visits and tumor assessments during and after treatment to evaluate the study drugs effects and tolerability.