Caceres

Researchers are evaluating ASTX030, a combination of azacitidine and cedazuridine, as a treatment for myeloid neoplasms including myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). This multi-phase study includes Phase 1 through Phase 3 monotherapy arms and Phase 1 and Phase 2 combination therapy arms with venetoclax. The study aims to assess pharmacokinetics, safety, efficacy, and drug interactions over an approximate duration of 8 years. The study treatments involve oral administration of ASTX030 and azacitidine, with some arms including subcutaneous azacitidine for comparison. Phase 1 monotherapy includes dose escalation and expansion stages, while Phase 2 and Phase 3 monotherapy arms are randomized crossover studies comparing oral ASTX030 to subcutaneous azacitidine. The combination therapy arms explore ASTX030 combined with venetoclax in participants with treatment-nafve AML, either in an open-label randomized exploratory setting or a single-arm study. Participants undergo evaluations including pharmacokinetic measurements such as total cycle area under the curve (AUC) for drug exposure, assessment of treatment-emergent adverse events, and investigator-assessed complete response rates. Monitoring occurs at multiple timepoints up to 36 months in some study arms. Safety, efficacy, and drug interaction assessments are integral throughout the study, with follow-up periods extending up to 8 years.

Researchers are evaluating the effects of pelacarsen (TQJ230), given as a monthly injection under the skin, in people with mild to moderate calcific aortic valve stenosis. This study aims to see if pelacarsen can safely slow the progression of this heart valve condition compared to a placebo. The trial is a phase 2, randomized, double-blind, placebo-controlled study conducted at multiple centers. Participants will receive either pelacarsen 80 mg or a matching placebo once a month. Before starting the treatment, they must have elevated lipoprotein(a) levels and be optimally treated for existing cardiovascular risk factors. The study focuses on those aged 50 to under 80 years with mild or moderate calcific aortic valve stenosis. During the 36 months of participation, researchers will monitor changes in peak aortic jet velocity and aortic valve calcium score to assess disease progression. Safety, tolerability, and the impact of the treatment will be evaluated. Participants will undergo regular assessments, including laboratory tests and clinical evaluations, to track heart valve condition and overall health throughout the study.

Researchers are evaluating a phase 1/2 open-label study to investigate the safety, pharmacokinetics, pharmacodynamics, and clinical effects of an oral drug called Enzomenib (DSP-5336) in patients with acute leukemia, including relapsed or refractory acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), ambiguous lineage acute leukemia, and in certain sites, high-risk myelodysplastic syndromes (MDS) or relapsed multiple myeloma (MM). The study also examines Enzomenib combined with standard AML treatments such as venetoclax plus azacitidine and the intensive chemotherapy 7+3 regimen in patients newly diagnosed with AML who have specific genetic mutations (MLL rearrangement or NPM1 mutation). Participants receive oral Enzomenib either alone or combined with other drugs: venetoclax and azacitidine for a nonintensive treatment group, gilteritinib for a certain relapsed AML group, or intensive chemotherapy with cytarabine and daunorubicin (7+3) for newly diagnosed AML patients. The study includes dose escalation and expansion phases to determine recommended doses for phase 2. Treatment schedules and doses are adjusted based on response and safety, with some patients enrolled in specialized cohorts according to their genetic markers. Throughout the study, participants undergo regular assessments including clinical exams, laboratory tests, bone marrow samples for genetic analysis, and monitoring for adverse events. Researchers measure safety outcomes such as adverse and serious adverse events, determine optimal dosing for phase 2, and evaluate treatment effectiveness by tracking complete response rates. Safety is monitored up to 30 days after the last dose, with dose recommendations made within four months of treatment start and response assessed around six months. The total participation time varies based on individual treatment and study phase.

Researchers are evaluating the safety, tolerability, and effectiveness of sonrotoclax alone and combined with other drugs in patients with relapsed or refractory multiple myeloma with a specific chromosomal translocation called t(11;14). This Phase 1b/2 study focuses on patients whose disease has returned or not responded to previous treatments, aiming to understand how well sonrotoclax works in these settings. The study assesses sonrotoclax given by mouth daily, either alone or combined with dexamethasone (given once weekly by mouth or intravenously), carfilzomib (weekly intravenous), daratumumab (weekly under the skin), or pomalidomide (daily by mouth). Different combinations are tested to find safe and effective dosing. The study includes dose-escalation and cohort-expansion phases to explore various treatment regimens. Participants will be closely monitored for side effects and treatment responses over time. Researchers will track dose-limiting toxicities during the first 28 days, adverse events up to 30 days after the last dose, and long-term responses over approximately 4 years. Assessments include measuring disease markers and overall response rates. Safety and efficacy data will guide future treatments for this patient population.

Researchers are evaluating treatments for adults with relapsed or refractory multiple myeloma who have previously received an anti-CD38 antibody and lenalidomide. The study compares the effectiveness of talquetamab combined with pomalidomide (Tal-P), talquetamab combined with teclistamab (Tal-Tec), and investigator's choice between two standard regimens: elotuzumab with pomalidomide and dexamethasone (EPd), or pomalidomide with bortezomib and dexamethasone (PVd). This Phase 3 trial aims to understand which combination best controls the disease progression. Participants will receive talquetamab as a subcutaneous injection, pomalidomide orally, teclistamab as a subcutaneous injection, elotuzumab intravenously, dexamethasone either orally or intravenously, and bortezomib as a subcutaneous injection. The study involves comparing these combinations with varying administration routes. The trial includes multiple treatment arms to assess different drug combinations in patients who have undergone 1 to 4 prior therapies. During the study, participants will be monitored for progression-free survival up to 3 years and 5 months. Researchers will regularly assess disease status, treatment response, and safety. Participants' performance status will be evaluated, and adherence to treatment and potential side effects will be carefully tracked. This long-term observation will help determine how well each treatment combination controls the disease over time.

Researchers are evaluating a Phase 2 study called PUMA-ALI-1201 to find the optimal dose of alisertib combined with endocrine therapy for adults with hormone receptor-positive, HER2-negative metastatic or recurrent breast cancer. Participants have experienced disease progression after at least two prior endocrine therapy treatments. The study also aims to assess the safety, effectiveness, pharmacokinetics of alisertib combined with endocrine therapy, and to identify biomarker-defined subgroups that may benefit most from this combination treatment. Participants will receive alisertib tablets orally twice daily on days 1-3, 8-10, and 15-17 of each 28-day cycle. They will also receive investigator-selected endocrine therapy according to approved dosing schedules, which may include daily oral tablets of anastrozole, letrozole, exemestane, tamoxifen, or intramuscular injections of fulvestrant on specified days. The combination treatment will be administered in repeated 28-day cycles. Throughout the study, researchers will monitor responses to treatment by measuring outcomes such as objective response rate, duration of response, disease control rate, progression-free survival, and overall survival for up to 48 months. Safety will be tracked by recording treatment-emergent adverse events from first dose through 28 days after the last dose. The study includes regular assessments to evaluate treatment effects, side effects, and participant well-being over the course of the trial.

Researchers are evaluating the combination of bleximenib, venetoclax (VEN), and azacitidine (AZA) compared to placebo with venetoclax and azacitidine alone in treating adults newly diagnosed with acute myeloid leukemia (AML) who have specific gene mutations (NPM1 or KMT2A) and are not eligible for intensive chemotherapy. This is a phase 3 randomized, double-blind, placebo-controlled study focusing on participants with AML harboring these genetic abnormalities. The study aims to assess treatment effectiveness by measuring complete remission rates and overall survival. Bleximenib and venetoclax are given orally, while azacitidine is administered either intravenously or under the skin. Participants will receive either the combination of bleximenib, venetoclax, and azacitidine or placebo with venetoclax and azacitidine, following a rigorous treatment schedule. The study includes an initial treatment period where the effects of these drugs are compared to determine their impact on AML with the given mutations. Participants will be closely monitored through regular assessments, including evaluations of remission status and survival over a period of up to 4 years and 1 month. Safety and treatment responses will be tracked throughout the study. Participants must consent to follow the study procedures and agree to contraception requirements during and after treatment. The trial involves continuous observation to gather comprehensive data on treatment outcomes and participant health.

Researchers are evaluating the effectiveness of camizestrant compared to standard endocrine therapy in patients with early breast cancer that is estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-). These patients have an intermediate or high risk of cancer recurrence and have already completed local treatments such as surgery and possibly chemotherapy, alongside at least 2 years and up to 5 years of standard adjuvant endocrine therapy. The study is a Phase III, open-label trial designed to assess outcomes over a long term. Participants will be randomly assigned to receive either camizestrant, an oral selective estrogen receptor degrader, or one of several standard endocrine therapies including tamoxifen, anastrozole, letrozole, or exemestane, administered according to local approved guidelines. The treatment duration for both groups is planned to last 60 months. Eligible patients may have previously used CDK4/6 inhibitors, and the study will specifically include those with intermediate or high risk of recurrence as determined by clinical and biological markers. During the study, participants will be monitored for up to 10 years from the last patient's randomization to evaluate invasive breast cancer-free survival. Additional outcomes include invasive disease-free survival, distant relapse-free survival, overall survival, safety, and clinical outcome assessments. The study involves ongoing assessments of health status, treatment effects, and safety to determine the long-term benefits and risks of camizestrant compared to standard therapies.

Researchers are evaluating the effectiveness, safety, and tolerability of mavorixafor in people aged 12 and older who have congenital or acquired primary autoimmune and idiopathic chronic neutropenic disorders. These participants experience repeated and/or serious infections due to low neutrophil levels. The study aims to show clinical benefit by increasing circulating neutrophils and reducing infection rates. Participants will continue their existing treatments, which may include granulocyte-colony stimulating factor (G-CSF), immunoglobulin replacement, prophylactic antibiotics, or observation without active treatment. They will be randomly assigned to receive either mavorixafor or a placebo, with both drugs given according to a set schedule. The study is double-blind and placebo-controlled, conducted across multiple centers. During the study, researchers will monitor participants for up to 52 weeks, focusing on the annual infection rate and the number of participants achieving a positive response in absolute neutrophil count. Participants will undergo regular assessments, including blood tests to measure neutrophil levels and evaluations for infections. The study includes safety monitoring and requires participants to maintain stable doses of their background therapies unless safety concerns arise.

Researchers are studying the rate and severity of specific eye-related side effects caused by mirvetuximab soravtansine (MIRV) in women with recurrent ovarian cancer that has high folate receptor alpha (FRα) expression. This includes both platinum-sensitive and platinum-resistant ovarian cancer types. The study aims to assess different strategies to prevent these eye side effects through thorough eye exams conducted before and during treatment. This is a Phase 2 randomized trial. Participants will be randomly assigned to one of two groups to receive different eye drop treatments to reduce eye side effects: primary prophylactic steroid eye drops or primary prophylactic vasoconstricting eye drops. All participants receive mirvetuximab soravtansine, an antibody drug conjugate targeting FRα, with additional lubricating eye drops given at least 15 minutes after the steroid or vasoconstricting drops. The treatments are self-administered as prescribed by the study doctor. During the study, participants will undergo regular eye exams and monitoring to track any eye problems related to the treatment. Researchers will count how many participants develop moderate or worse eye side effects up to 18 weeks or until 30 days after treatment ends. Safety and eye health will be closely followed, including assessments of vision and any adverse events. The study focuses on women aged 18 and older with recurrent ovarian cancer who meet specific health and treatment history criteria.