Duarte

Researchers are investigating the drug bezuclastinib in an open-label, two-part Phase 2 study for patients with Advanced Systemic Mastocytosis (AdvSM), including 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, and how the drug behaves in the body for these serious conditions. Bezuclastinib is given orally as tablets taken continuously in 28-day cycles. The study has two parts: Part I focuses on identifying safe and tolerable doses of bezuclastinib over 18 months, while Part II evaluates its effectiveness by measuring the objective response rate and confirming the relationship between drug exposure and response during another 18-month period. Participants will undergo assessments including clinical evaluations, laboratory tests, and monitoring of their disease status to determine treatment effects and safety. Researchers will track the drug's impact on the disease and patient health throughout the study, which involves continuous treatment and follow-up over the specified time frames.

PRIMARY OBJECTIVE: I. To evaluate the immune response induced by the combination of lutetium Lu 177 vipivotide tetraxetan (177\^Lu-PSMA-617) and sipuleucel-T, using changes in anti-prostatic acid phosphatase (PAP) immunoglobulin G (IgG) antibody titers. SECONDARY OBJECTIVES: I. To evaluate anti-PA2024 antibody titers in patients receiving 177\^Lu-PSMA-617 alone versus in combination with sipuleucel-T. II. To assess the safety and tolerability of 177\^Lu-PSMA-617 plus sipuleucel-T. III. To evaluate the clinical efficacy of 177\^Lu-PSMA-617 alone versus in combination with sipuleucel-T. EXPLORATORY OBJECTIVES: I. To characterize the pharmacokinetics (PK) of 177\^Lu-PSMA-617 plus sipuleucel-T in the blood. II. To determine the impact of 177\^Lu-PSMA-617 in combination with sipuleucel-T on systemic immunomodulation. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A (CONTROL GROUP): Patients receive 177\^Lu-PSMA-617 intravenously (IV). Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, PSMA positron emission tomography (PET)/computed tomography (CT), bone scan, and magnetic resonance imaging (MRI) throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study. ARM B (EXPERIMENTAL GROUP): Patients receive 177\^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Starting during week 8 of treatment, patients receive sipuleucel-T IV over 1 hour. Treatment repeat every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo leukapheresis, blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study. After completion of study treatment, patients are followed up at 30 days, every 3 months for up to 1 year then every 6 months until progression followed by survival follow until death or withdrawal of consent.

Researchers are evaluating a new conditioning treatment combining 225Ac-DOTA-Anti-CD38 daratumumab, fludarabine, melphalan, and total marrow and lymphoid irradiation (TMLI) for donor stem cell transplant in patients with high-risk acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). This phase I trial focuses on testing the safety, side effects, best dose, and potential effectiveness of this combination. Daratumumab is a monoclonal antibody targeting CD38 on certain immune and cancer cells, and when linked to a radioactive substance, it may help kill cancer cells. The study also aims to determine the maximum tolerated dose and recommended phase II dose of this approach. During the treatment, patients receive intravenous daratumumab followed by indium In 111-DOTA-daratumumab and then actinium Ac 225-DOTA-daratumumab approximately 15 days before transplant. Total marrow and lymphoid irradiation is given twice daily over four days, followed by fludarabine over three days and melphalan on the day before the stem cell transplant. Additionally, patients receive graft-versus-host disease (GVHD) prevention with sirolimus and tacrolimus starting one day before transplant. Several scans and biopsies are performed throughout the study, including CT scans, nuclear and SPECT imaging, echocardiography or MUGA scans, and bone marrow sampling. Participants are closely monitored after treatment with visits twice weekly for the first 100 days post-transplant, then twice monthly for six months, and monthly thereafter until immunosuppressive therapy is stopped without GVHD, with at least yearly follow-up for two years. Researchers track adverse events, survival outcomes, relapse rates, and pharmacokinetics of the radioimmunotherapy. Blood samples and imaging help assess treatment safety and effectiveness over time.

Researchers are evaluating 64Cu-LNTH-1363S, a radiolabeled FAP inhibitor, in patients with sarcomas or gastrointestinal tract cancers. This multicenter, open-label Phase 1/2a study aims to assess the safety and tolerability of the agent, establish dosimetry, and identify the optimal imaging dose and timing. The study also compares the imaging biodistribution of 64Cu-LNTH-1363S with FAP expression measured by immunohistochemistry in tumor tissues. The study is divided into two parts. Part 1 involves six patients with metastatic sarcomas receiving a single dose of approximately 8 ± 1 mCi of 64Cu-LNTH-1363S, followed by serial PET/CT scans at multiple timepoints on the intervention day to determine biodistribution and optimal imaging parameters. Part 2 includes twenty patients with non-metastatic, operable sarcomas or gastrointestinal cancers planned for surgery within 60 days. These patients undergo imaging with the agent, and tissue samples collected during surgery are analyzed for FAP expression. Both parts monitor cardiac safety through ECG assessments. Participants will go through screening up to 14 days before intervention, receive the imaging dose on one day, and have safety follow-ups for 1 to 7 days depending on the study part. Assessments include serial PET/CT imaging at specified timepoints post-dose, tumor tissue sampling for immunohistochemistry, and cardiac monitoring for changes in heart rate and QT intervals. Part 2 extends up to 10 to 11 weeks to cover the surgical tissue collection period. The study measures biodistribution, dose optimization, correlation with FAP expression, and cardiac safety throughout the participation period.

Hepatocellular carcinoma (HCC) is a serious liver cancer often diagnosed at late stages, leading to poor outcomes. Early detection is crucial for improving survival, but current non-invasive biomarkers like alpha-fetoprotein (AFP) have limited sensitivity, especially for early-stage HCC. This research aims to develop and validate a new blood test using cell-free tRNA-derived small RNAs (cf-tsRNAs) to better detect early-stage HCC and guide timely treatment decisions. The study involves analyzing blood samples from patients with confirmed HCC using advanced RNA sequencing and PCR-based tests. Researchers will identify and validate specific cf-tsRNA biomarkers that distinguish HCC from non-disease controls. Machine learning will be used to create a diagnostic classifier from these biomarkers, aiming for a highly sensitive and non-invasive liquid biopsy test. Participants will provide blood samples before any curative treatment begins. Researchers will monitor the sensitivity of the cf-tsRNA assay over about one year. The study focuses on measuring how accurately the test detects HCC early, which could help doctors decide on surgery or additional therapies. This process includes detailed biomarker testing and ongoing assessment to improve early liver cancer diagnosis.

Researchers are evaluating a new treatment called ifinatamab deruxtecan (I-DXd) for men with metastatic castration-resistant prostate cancer (mCRPC). This study compares I-DXd to chemotherapy to see if it helps people live longer overall and live longer without their cancer worsening. It is a Phase 3, open-label trial focused on patients who have progressed on prior therapies and have evidence of metastatic disease. Participants receive either I-DXd through an intravenous infusion every 3 weeks or docetaxel chemotherapy administered every 3 weeks. Prednisone tablets are also given daily as part of the treatment plan. Before each I-DXd dose, premedication is provided to help prevent nausea and vomiting using a combination of drugs such as corticosteroids and anti-nausea medicines. Treatment continues until disease progression, unacceptable side effects, or other reasons to stop. During the study, researchers monitor overall survival and how long patients live without their cancer progressing, for up to about 36 months. Participants undergo tumor tissue collection, scans, and assessments to track disease status and side effects. Safety is closely watched throughout treatment. The study includes men aged 18 and older with confirmed prostate cancer and metastatic disease who have previously received certain hormone therapies but no prior taxane chemotherapy for mCRPC.

Researchers are looking for ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL). DLBCL is a fast-growing blood cancer that affects B-cells. GCB is a type of DLBCL that affects young B-cells that are still maturing. The goal of this study is to learn if more people who receive zilovertamab vedotin (MK-2140) and R-CHP have the cancer respond (go away) than those who receive polatuzumab vedotin and R-CHP.

Researchers are evaluating a culturally-tailored, home-based physical activity program designed to improve physical fitness in Hispanic or Latino/Latina adolescent and young adult childhood cancer survivors. These survivors may face long-term effects such as weight gain, fatigue, and reduced fitness after cancer treatment, with Hispanic or Latino/Latina individuals potentially at higher risk. The study aims to increase moderate to vigorous physical activity (MVPA) through a mobile health and social media intervention. The study has two stages. Stage 1 involves developing the intervention using feedback from 20 Latinx survivors who speak either English or Spanish. Stage 2 is a randomized controlled trial comparing the intervention group with a control group that only uses a Fitbit tracker. The intervention group receives Fitbit trackers, weekly reminders, goal-setting sessions, social media peer support 2-3 times a week, badges, monthly Zoom meetings, and may choose a physical activity partner who also receives support. After 12 weeks, a 4-week maintenance phase continues these supports with less structure. The control group wears a Fitbit daily for 12 weeks without additional support. Participants wear Fitbit trackers daily, attend weekly sessions, post on social media, and complete interviews and questionnaires. Researchers measure changes in physical activity levels, sedentary time, quality of life, and cardiometabolic health indicators. Data is collected using Fitbit devices, interviews, and surveys, with follow-up over 12 weeks plus maintenance. Safety and acceptability of the intervention are also assessed throughout the study.

Researchers are evaluating bulumtatug fuvedotin for treating patients with recurrent or metastatic triple-negative breast cancer who have previously received antibody-drug conjugates with a topoisomerase inhibitor. This phase Ib, open-label, multicenter study aims to assess the effectiveness of this treatment in patients who have had prior therapy including taxanes and no more than three lines of cytotoxic treatment in the advanced setting. Patients must have measurable disease and meet specific health and organ function requirements.

Researchers are evaluating the safety and tolerability of increasing doses of PTX-912 in adult patients with locally advanced or metastatic solid tumors. The study also aims to assess the pharmacokinetics and immune response to PTX-912, as well as its preliminary anti-tumor effects. This is a first-in-human, Phase 1 clinical trial focusing on patients who have progressed on all available standard treatments or have no reasonable standard care options. Participants receive PTX-912 as an intravenous infusion every two weeks. Treatment continues until the disease worsens, unacceptable side effects occur, or a maximum of 12 months of therapy is reached. The study includes a dose escalation phase to find safe dose levels, followed by a dose expansion phase to further evaluate the treatment. During the study, patients undergo regular assessments including safety monitoring for dose limiting toxicities within the first 28 days, laboratory tests to check organ and bone marrow function, and imaging to measure tumor response. Researchers also monitor immune responses and drug levels in the body. Participants are expected to comply with scheduled visits and procedures throughout their involvement in the trial.