Santa Barbara

Researchers are evaluating sotatercept as a potential treatment for pulmonary arterial hypertension (PAH), a condition where blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and overworking the heart. PAH symptoms include difficulty breathing and reduced ability to be active. Current standard treatments address symptoms but do not stop disease progression. This Phase 3 study focuses on the long-term safety and tolerability of sotatercept when added to standard PAH therapy. Participants in this long-term follow-up study receive sotatercept through subcutaneous injections every three weeks. Only individuals who completed prior sotatercept PAH studies without early discontinuation may join. This study continues the observation and assessment of participants over an extended period to learn about the effects and safety of sotatercept combined with background PAH treatments. During the study, participants will be regularly monitored for adverse events, treatment discontinuations, and the presence of anti-drug antibodies for up to approximately 90 months. Laboratory tests will evaluate blood components such as platelets, hemoglobin, creatinine, bilirubin, and liver enzymes. Changes from baseline in body weight, blood pressure, and electrocardiogram readings will also be tracked. The study involves adherence to visit schedules and compliance with study procedures to ensure comprehensive long-term safety data collection.

Researchers are evaluating the safety and effectiveness of combining ruxolitinib, steroids, and lenalidomide in patients with relapsed or refractory multiple myeloma (MM) who show disease progression. Multiple myeloma is a cancer of plasma cells in the bone marrow, and despite advances in treatment, it remains incurable. This phase 1, open-label, multicenter study aims to explore new therapeutic options by targeting the JAK/STAT pathway involved in MM cell growth and survival. Participants will receive oral ruxolitinib daily on days 1 through 28, lenalidomide on days 1 through 21, and methylprednisolone daily on days 1 through 28 of each treatment cycle. The combination therapy is being studied to determine the maximum tolerated dose of ruxolitinib when used with steroids and lenalidomide. The study also monitors treatment-emergent adverse events over a period of up to 54 months. Throughout the study, participants will undergo various assessments including laboratory tests to monitor blood counts, liver and kidney function, and disease markers. Researchers will evaluate safety, tolerability, and efficacy by tracking adverse events and disease progression. Participants must be able to follow the study schedule and provide informed consent. The study also involves registration in the REVLIMID REMS program for safety monitoring related to lenalidomide use.

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.

The primary purpose of the study is to assess how well amivantamab in combination with lazertinib or in combination with chemotherapy works (antitumor activity) in participants with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC; that is one of the major types of lung cancer).

Researchers are evaluating ART0380, an oral drug that blocks ATR kinase, in people with advanced or metastatic solid tumors including ovarian, peritoneal, fallopian tube, endometrial, colorectal, pancreatic ductal adenocarcinoma, and acinar cell carcinoma. The study aims to find the safe dose of ART0380 alone and combined with chemotherapy drugs gemcitabine or irinotecan, understand side effects, and assess its effectiveness. This open-label Phase I/IIa trial includes participants whose cancers have DNA repair defects or lack ATM protein and some specific cancer types. Participants receive ART0380 by mouth in 21-day cycles either intermittently (several days on then off) or continuously daily. Gemcitabine is given on days 1 and 8, and irinotecan is given by 90-minute infusion on the same days in combination groups. The study has different parts to find dosing levels and to evaluate safety, tolerability, pharmacokinetics, and initial effectiveness of ART0380 alone or combined with the chemotherapy drugs. During the study, participants undergo regular evaluations including scans every 6 to 9 weeks to monitor tumor response, and safety assessments for side effects throughout treatment and up to 30 days after the last dose. Researchers track adverse events and measure progression-free survival and tumor response rates over up to 2 years. Participants are expected to be available and willing to follow study procedures and assessments during the trial period.

Researchers are evaluating the efficacy and safety of a drug called azenosertib (ZN-c3) in women with platinum-resistant, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. This Phase 2 study focuses on patients whose tumors test positive for Cyclin E1 protein, determined by a specific assay developed by the sponsor. The study aims to understand how well azenosertib works in this group and its safety profile. The study involves administering azenosertib orally to participants. It is divided into two parts: Part 1 included all patients regardless of biomarker status and has completed enrollment; Part 2 requires tumors to be Cyclin E1 positive. Participants receive azenosertib and are monitored throughout the study according to the protocol. Participants will be involved in various assessments including tumor measurements following RECIST version 1.1 criteria up to about 12 months after the last participant enrolls. Researchers will track the objective response rate to evaluate tumor response. Safety and efficacy evaluations, along with monitoring of side effects and overall health, will take place during the study period to gather comprehensive data on the treatment.

Researchers are evaluating the safety and effectiveness of neoadjuvant carboplatin combined with mirvetuximab soravtansine in adult women with folate receptor alpha (FRα)-expressing advanced-stage serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. This is a single-arm Phase 2 study involving about 140 participants across approximately 80 sites in the United States. The study focuses on advanced disease stages III and IV, with FRα expression confirmed in tumor cells. Participants will receive intravenous infusions of mirvetuximab soravtansine together with carboplatin on day 1 of each 21-day cycle, continuing for up to 6 to 9 cycles. Bevacizumab may also be given as an intravenous infusion if the investigator decides it is appropriate. The total duration of the study is about 3 years, during which treatments and responses will be closely monitored. During the study, participants will attend regular visits at hospitals or clinics for medical evaluations including blood tests, scans, and safety assessments. Researchers will track tumor response using independent central review over the course of up to 3 years. The study involves frequent medical monitoring to assess treatment effects and participant safety.

Researchers are evaluating treatments for children and young adults with newly diagnosed acute myeloid leukemia (AML), with or without FLT3 gene mutations. This phase III trial compares standard chemotherapy using daunorubicin, cytarabine, and gemtuzumab ozogamicin to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or the FLT3 inhibitor gilteritinib. The study aims to find out which treatment improves event-free survival, overall survival, and minimal residual disease rates, while also monitoring heart function and other effects during and after therapy. Participants are assigned to different treatment arms based on their AML risk group and FLT3 mutation status. Treatments include combinations of intravenous and intrathecal chemotherapy drugs such as cytarabine, daunorubicin, gemtuzumab ozogamicin, dexrazoxane, etoposide, mitoxantrone, asparaginase, and methotrexate. Gilteritinib is given orally to patients with FLT3 mutations alongside chemotherapy. Treatment phases include multiple induction cycles, intensification cycles, and for some, allogeneic stem cell transplantation followed by maintenance therapy with gilteritinib. Throughout the study, participants undergo regular assessments including blood tests, bone marrow biopsies, imaging scans like MRI and CT, cardiac function monitoring, and neuropsychological testing. Researchers track event-free survival up to 3 years, changes in heart function, leukemia response, and neurocognitive effects. Optional cognitive tests are offered at several time points. The study also collects blood samples for pharmacokinetic and biomarker analyses to better understand treatment effects and safety.

Researchers are evaluating whether adding immunotherapy drugs brentuximab vedotin and nivolumab to standard chemotherapy, with or without radiation, can improve survival for patients aged 5 to 60 years with newly diagnosed stage I or II classical Hodgkin lymphoma. This phase III trial compares outcomes in groups based on their early response to initial chemotherapy, aiming to understand if immunotherapy can lead to better progression-free survival and overall survival compared to standard treatment alone. The study also looks at side effects, quality of life, and long-term health impacts across different patient groups. Participants first receive two cycles of standard ABVD chemotherapy every 28 days, followed by imaging to classify their response as rapid or slow early responders and their risk status as favorable or unfavorable. Based on these factors, patients are assigned to one of eight treatment arms that include either continued standard chemotherapy regimens or immunotherapy with brentuximab vedotin and nivolumab, sometimes combined with involved-site radiation therapy. Treatments are given intravenously or orally depending on the drugs, and cycles typically last 28 days. Imaging and blood samples are collected regularly throughout the study. Throughout the trial, participants undergo frequent scans such as FDG-PET, CT, MRI, and PET-CT to monitor their disease status. Blood samples and questionnaires assess treatment effects and quality of life. After completing treatment, patients have scheduled follow-up visits every 3 months for the first year, then every 6 months for two years, and annually up to 12 years to track long-term outcomes, side effects, and survival. The main measurements focus on progression-free survival, overall survival, treatment-related adverse events, and patient-reported experiences.

Researchers are evaluating the effectiveness, safety, and pharmacokinetics of the Port Delivery System (PDS) with ranibizumab compared to standard intravitreal ranibizumab injections in adults with diabetic macular edema (DME). This Phase III, multicenter, randomized study aims to compare PDS treatment every 24 weeks with injections every 4 weeks. A substudy will assess the safety of re-implanting the updated PDS and performing refill-exchange procedures in participants previously enrolled in the main study. Participants will receive either the PDS implant pre-filled with ranibizumab or intravitreal ranibizumab injections according to their assigned group. Treatments will be administered on a set schedule specific to each arm. The substudy involves re-implantation of the updated PDS and monitoring post-procedure. The PDS refill exchange is also part of the treatment plan for some participants. Throughout the study, participants will undergo assessments including vision tests using the ETDRS chart to measure changes in best-corrected visual acuity (BCVA). Safety will be monitored by tracking ocular and systemic adverse events, device-related effects, and any serious complications up to 72 weeks after treatment or re-implantation. The study evaluates both short-term and long-term safety and efficacy outcomes over the full duration of participation.