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Researchers are evaluating the short-term and long-term safety and effectiveness of belimumab in adults diagnosed with early systemic lupus erythematosus (SLE) who have positive autoantibodies and continue to have active disease despite stable initial treatment. This phase 4, prospective, open-label study aims to describe how belimumab works in this specific group over a three-year period. Participants will receive belimumab (GSK1550188) administered by subcutaneous injection. There is one treatment arm where all participants will receive this drug. The study lasts for three years, during which participants will be regularly monitored to assess disease activity and treatment safety. During the study, participants will undergo various assessments including clinical evaluations to measure disease activity, laboratory tests, and questionnaires to track health status. The main outcome is the percentage of participants who achieve Lupus Low Disease Activity State (LLDAS) by week 52. Safety and efficacy will be closely monitored throughout the study period, with follow-up visits and evaluations scheduled at regular intervals.

Researchers are evaluating the drug disitamab vedotin, alone or combined with pembrolizumab, to treat urothelial cancer that expresses HER2. This cancer is locally advanced, cannot be removed by surgery, or has spread to other parts of the body. The study aims to see how well the drug works and how safe it is for participants by monitoring side effects and treatment responses. Participants will receive disitamab vedotin through an intravenous (IV) infusion every two weeks. Pembrolizumab, when given, is administered by IV on the first day of each six-week cycle. The study includes several groups, called cohorts, each with different treatment histories and eligibility criteria. Treatment and evaluation may continue for about two years. During the study, participants will have regular tests including scans to measure tumor response, lab tests, heart function checks, and monitoring for adverse events. Researchers will also track drug levels in the blood and any changes in heart function. The study will assess confirmed tumor responses and safety outcomes over approximately two years, with close monitoring to understand how participants respond to the treatments and any side effects experienced.

Researchers are evaluating whether tucatinib combined with trastuzumab and mFOLFOX6 works better than the standard treatments for people with HER2 positive metastatic colorectal cancer, which is cancer that has spread or cannot be removed by surgery. This phase 3 study also aims to identify the side effects that may occur with this drug combination. Participants must have HER2 positive disease confirmed by testing and measurable cancer according to specific criteria. Participants will be randomly assigned to one of two groups. One group will receive tucatinib taken orally twice daily along with intravenous trastuzumab and the mFOLFOX6 chemotherapy regimen, which includes oxaliplatin, leucovorin or levoleucovorin, and fluorouracil given by IV every two weeks. The other group will receive standard care, which could be mFOLFOX6 alone or combined with either bevacizumab or cetuximab, both given by IV on specific schedules. Treatment continues as per the study protocol. During the study, participants will be monitored for progression-free survival up to about three years using imaging reviewed by independent experts. Researchers will assess side effects and disease response. Participants must be able to provide tumor tissue samples for testing and have a good performance status. The study includes brain imaging to check for metastases and monitors safety closely throughout the treatment period.

PRIMARY OBJECTIVES: I. To compare event free survival post reinduction (EFS PR) between blinatumomab vs. blinatumomab/nivolumab in Group 4 patients aged ≥ 1 to \<31 years old with first relapse of CD19+ B ALL. II. To compare EFS PR (EFS post-reinduction) between consolidation with blinatumomab vs. blinatumomab/nivolumab in Group 3 patients aged \>= 1 to \< 31 years old with first relapse of CD19+ B ALL. SECONDARY OBJECTIVES: I. To evaluate the safety and tolerability of blinatumomab/nivolumab in patients aged \>= 1 to \< 31 years old with first relapse of CD19+ B ALL. EXPLORATORY OBJECTIVES: I. In Group 4 patients, compare EFS PR between blinatumomab monotherapy and blinatumomab/nivolumab arms as compared to similar patients treated on the predecessor trial AALL1331. II. In Group 4 patients, compare toxicity as defined by grade 3 or greater adverse events during the first cycle of blinatumomab or blinatumomab/nivolumab. III. In Group 4 patients, compare MRD negative second remission (Rem-2) rate after the first cycle of immunotherapy between blinatumomab monotherapy and blinatumomab/nivolumab arms. IV. In patients with Down syndrome (DS) with first relapse of B-ALL, describe the safety, tolerability and efficacy (as defined by MRD negative second remission, Rem-2) after up to two cycles of blinatumomab/nivolumab. V. With each Group, perform subset analyses of EFS and overall survival (OS) based on features including degree of marrow disease at relapse, age, sex, body mass index, cytogenetics, site(s) of relapse, percent peripheral blasts at relapse and absolute lymphocyte count at first relapse. OUTLINE: Patients \>= 18 years old with marrow +/- extramedullary (EM) relapse of any duration after initial diagnosis, or patients \< 18 years old with marrow +/- EM relapse \< 24 months after initial diagnosis are assigned to Group 1. Patients \< 18 years old with marrow +/- EM relapse \>= 24 months from initial diagnosis, or all isolated extramedullary (IEM) relapses \>= 1 to \< 31 years old are assigned to Groups 2-3 re-induction. Patients with DS are assigned to Arm G. NOTE: Patients in Group 1 and DS patients with white blood cells (WBC) \>= 30,000/uL, CNS 2/3 disease, or testicular disease must first receive 1 of 3 pre-immunotherapy treatments. Starting with amendment 4C (9/19/2024), patients with DS are assigned to group 3 or 4. Patients \< 18 years with bone marrow first relapse ≥ 36 months from initial diagnosis with MRD \<0.1% after VXLD reinduction or with isolated CNS/testicular extramedullary relapse occurring ≥ 18 months from initial diagnosis with MRD \<0.1% after VXLD reinduction are assigned to group 3. Patients who do not meet criteria for group 3 will be assigned to group 4. Patients with Down syndrome ≥ 1 to \< 31 years of age with first bone marrow relapse of B ALL are assigned to arm G. PRE-IMMUNOTHERAPY TREATMENT FOR PATIENTS WITH WBC \>= 30,000/uL (CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G) : Patients receive methotrexate (MTX) intrathecally (IT) or cytarabine IT or intrathecal triple therapy (ITT) consisting of MTX, hydrocortisone sodium succinate, and cytarabine IT at the time of diagnostic lumbar puncture (LP) or on day 1 (if intrathecal therapy is given with relapse diagnostic LP \< 7 days prior to the start of protocol therapy). Patients also receive dexamethasone intravenously (IV) or orally (PO) twice daily (BID) on days 1-5, vincristine sulfate via infusion or IV push over 1 minute on day 1. Patients with DS also receive leucovorin calcium PO or IV every 6 hours (q6h) for 2 doses on day 2 or at 24 and 30 hours after each IT administration. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 8 and no later than Day 15. PRE-IMMUNOTHERAPY TREATMENT FOR CNS 2/3 DISEASE (CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G): Patients receive MTX IT or cytarabine IT twice weekly (Q2W) for 5-7 doses or Intrathecal Triple Therapy (ITT) IT Q2W for 3-4 doses until patient is CNS 1. Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses at 24 and 30 hours after each IT administration. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 15 and no later than Day 24. PRE-IMMUNOTHERAPY TREATMENT FOR TESTICULAR DISEASE(CLOSED TO ACCRUAL 9/19/2024 EXCEPT FOR ARM G): Patients receive MTX IT, cytarabine IT, or ITT IT on days 1 and 15 (day 1 may be omitted if intrathecal therapy is given with relapse diagnostic LP \< 7 days prior to the start of protocol therapy). Patients with DS also receive leucovorin calcium PO or IV q6h for 2 doses on days 2 and 16 or at 24 and 30 hours after each IT administration. Males with testicular disease at relapse undergo radiation once daily (QD) for a total of 12 fractions over 12 days. Patients should proceed to the next cycle when CNS 1 and no testicular disease is present, no sooner than Day 15 and no later than Day 22. GROUP 1 (CLOSED TO ACCRUAL 9/19/2024): Patients are randomized to Arm A or Arm B. ARM A: Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1-2, MTX IT, cytarabine IT, or ITT IT on days 1, 15, and 36 of cycle 1 (MTX, cytarabine, and ITT on day 1 may be omitted if intrathecal therapy was given \< 7 days prior to the start of this cycle), and MTX IT, cytarabine IT, or ITT IT on days 15 and 36 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. ARM B: Patients receive dexamethasone, blinatumomab, and MTX, cytarabine, or ITT as in Arm A. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. GROUPS 2-4 VXLD REINDUCTION: Patients receive vincristine sulfate via infusion or IV push over 1 minute on days 1, 8, 15, and 22, dexamethasone PO or IV on days 1-14, doxorubicin hydrochloride IV over 1-15 minutes on day 1, MTX IT on days 1, 8, and 29 (day 1 IT may be omitted if intrathecal therapy is given with relapse diagnostic LP \< 7 days prior to the start of this cycle) (days 8 and 29 for CNS 1 patients at relapse only), pegaspargase intramuscularly (IM) or IV over 1-2 hours on days 2 and 16 or calaspargase IV over 1-2 hours on day 2 (for patients ≤ 22 years), cytarabine IT on days 4 and 11 (CNS 2 patients at relapse only), then Q2W until 3 consecutive samples are clear of blasts, and ITT IT on days 8, 15, 22, and 29 (CNS 3 patients at relapse only). Treatment continues in the absence of disease progression or unacceptable toxicity. GROUP 2 (CLOSED TO ACCRUAL 9/19/2024): The following patients are randomized to Arm C or Arm D: 1) \>= 1 to \< 31 years old, IEM relapse \< 18 months from diagnosis, regardless of MRD after Re-Induction. 2) \< 18 years old with marrow relapse \>= 24 to \< 36 months from diagnosis regardless of MRD after Re-Induction, 3) \>= 1 to \< 31 years old, IEM relapse \>= 18 months, and MRD \>= 0.1% after Re-Induction, 4) \< 18 years old with marrow relapse \>= 36 months, and MRD \>= 0.1% after Re-Induction. ARM C: Patients receive dexamethasone PO or IV on day 1 of cycle 1, blinatumomab via continuous IV infusion on days 1-28 of cycles 1 and 2, and MTX IT on days 1 and 15 of cycles 1 and 2 (day 1 may be omitted from cycle 1 if intrathecal MTX is given \< 7 days prior to the start of cycle 1 ). Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. ARM D: Patients receive dexamethasone, blinatumomab, and MTX as in Arm C. Patients also receive nivolumab IV over 30 minutes on days 11 and 25 of cycle 1 and days 1 and 15 of cycle 2. Treatment repeats every 36 days for 2 cycles in the absence of disease progression or unacceptable toxicity. NOTE: Patients with MRD \< 0.01% after cycle 1 may stop study treatment or may choose to continue to cycle 2. Patients with MRD \>= 0.01% after cycle 1 proceed to cycle 2. GROUP 3: Patients are randomized to Arm E or Arm F. ARM E: IMMUNOTHERAPY CYCLES 1-2: Patients receive dexamethasone PO or IV on day 1 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15 (day 1 may be omitted from cycle 1 if intrathecal therapy is given \< 7 days prior to the start of this cycle). Immunotherapy cycles 1-2 alternate with Consolidation cycles 1-2. CONSOLIDATION: Patients receive dexamethasone PO or IV on days 1-5, methotrexate IV, over 24 hours, on days 8 and 22, methotrexate IT on days 8 and 22 (CNS 1/2 at relapse only) or ITT IT on days 8 and 22 (CNS 3 at relapse only). INTENSIFICATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, mercaptopurine PO on days 1-42, methotrexate IV over 24 hours on days 8 and 22, cytarabine IV, over 3 hours on days 43 and 44, asparaginase erwinia recombinant IM or crisantaspase/asparaginase erwinia IM or IV over 1-2 hours on day 44, methotrexate IT on days 1 and 43 (CNS 1/2 at relapse only) or ITT IT on days 1 and 43 (CNS 3 at relapse only). IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, and MTX IT on days 1 and 15 (CNS 1/2 at relapse only) or ITT IT on days 1 and 15 (CNS 3 at relapse only). MAINTENANCE: Patients receive dexamethasone PO BID on days 1-5, 29-33, and 57-61, vincristine sulfate IV push over 1 minute or via infusion on days 1, 29, and 57, mercaptopurine PO on days 1-84, MTX IT on day 1 (CNS 1/2 patients at relapse only), ITT IT on day 1 (CNS 3 patients at relapse only), and MTX PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMORADIATION (FOR CNS 3 PATIENTS ONLY): Beginning between the first and second cycles of maintenance therapy, patients receive dexamethasone PO BID on days 1-7 and 15-21, vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours or calaspargase IV over 1-2 hours on day 1. Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional (D)-conformal radiation therapy (CRT) over 5 days per week for a total of 10 treatments. ARM F: IMMUNOTHERAPY CYCLES 1-2: Patients receive dexamethasone PO or IV on day 1 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11 of cycle 1 and on days 1 of cycles 2 and 3, and MTX IT on days 1 and 15 (CNS 1/2 patients at relapse only)(day 1 may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle) or , ITT IT on day 1 (CNS 3 patients at relapse only) (day 1 may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Immunotherapy cycles 1-2 alternate with Consolidation cycles 1-2. CONSOLIDATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, methotrexate IV, over 24 hours, on days 8 and 22, methotrexate IT on days 8 and 22 (CNS 1/2 at relapse only) or ITT IT on days 8 and 22 (CNS 3 at relapse only). INTENSIFICATION CYCLES 1-2: Patients receive dexamethasone PO on days 1-5, vincristine sulfate IV push over 1 minute or via infusion on day 1, mercaptopurine PO on days 1-42, methotrexate IV over 24 hours on days 8 and 22, cytarabine IV, over 3 hours on days 43 and 44, asparaginase erwinia recombinant IM or crisantaspase/asparaginase erwinia IM or IV over 1-2 hours on day 44, methotrexate IT on days 1 and 43 (CNS 1/2 at relapse only) or ITT IT on days 1 and 43 (CNS 3 at relapse only). IMMUNOTHERAPY CYCLE 3: Patients receive blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 1 and 15 and MTX IT on days 1 and 15. MAINTENANCE: Patients receive dexamethasone PO BID on days 1-5, 29-33, and 57-61, vincristine sulfate IV push over 1 minute or via infusion on days 1, 29, and 57, mercaptopurine PO on days 1-84, MTX IT on day 1 (CNS 1/2 patients at relapse only), ITT IT on day 1 (CNS 3 patients at relapse only), and MTX PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78. Treatment repeats every 12 weeks for 2 years from the start of Re-Induction therapy in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMORADIATION (FOR CNS 3 PATIENTS): Beginning between the first and second cycles of maintenance therapy, patients receive dexamethasone PO BID on days 1-7 and 15-21, vincristine sulfate IV push over 1 minute or via infusion on days 1, 8, and 15, and pegaspargase IM or IV over 1-2 hours or calaspargase IV over 1-2 hours on day 1. Patients with CNS 3 and isolated CNS relapse undergo cranial radiation in the form of 3-dimensional (D)-conformal radiation therapy (CRT) over 5 days per week for a total of 10 treatments. GROUP 4: Patients are randomized to arm H or arm I. ARM H: Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. ARM I: Patients receive dexamethasone PO or IV on day 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV, over 30 minutes on day 11 of cycle 1 and day 3 of cycle 2 and MTX IT on days 1 of cycle 1 only and days 15 and 36 ( for patients with CNS 1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. ARM G (DS PATIENTS): Patients receive dexamethasone PO or IV on days 1 and 8 of cycle 1 only, blinatumomab IV via continuous infusion on days 1-28, nivolumab IV over 30 minutes on days 11 of cycle 1 and day 3 of cycle 2, and MTX IT (for patients with CNS 1/2 at relapse only) or ITT on day 1 of cycle 1 only and days 15 and 36 (for patients with CNS 3 at relapse only) (day 1 IT therapy may be omitted from cycle 1 if intrathecal therapy is given with \< 7 days prior to the start of this cycle). Cycles repeat every 37 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo lumbar puncture, bone marrow biopsy and aspiration, and collection of blood, urine and cerebrospinal fluid throughout the study. After completion of study treatment, patients are followed up every 3 months for 1 year.

Researchers are evaluating the treatment outcomes of subcutaneous anifrolumab 120 mg once weekly as add-on therapy to antimalarials, with or without glucocorticoids (GCs), in patients with systemic lupus erythematosus (SLE) who have not previously used immunosuppressants or biologics. The study focuses on patients not in Lupus Low Disease Activity State (LLDAS) at enrollment and aims to describe clinical outcomes such as achieving DORIS remission, while also understanding GC tapering and withdrawal possibilities. This is a Phase 3, open-label, single-arm study. Approximately 275 participants aged 18 to 70 will receive anifrolumab subcutaneously once weekly for 52 weeks following a screening period of up to 35 days. Participants may increase their GC dose until week 4 based on investigator recommendation, then those on more than 5 mg/day GC at entry will attempt a taper to 5 mg/day over 12 weeks between weeks 5 and 40. Participants achieving DORIS remission for two visits will then attempt complete GC withdrawal with a 12-week taper. After week 41 until study end, no further GC dose reductions will occur. Following treatment, a 12-week safety follow-up is included for those not continuing anifrolumab. Participants will undergo assessments including clinical evaluations, laboratory tests, and questionnaires to monitor disease activity, remission status, and safety. Researchers will measure attainment of DORIS remission at week 52 as the primary outcome. Study evaluations will include ANA and other antibody testing, infection screening, HPV testing, and adherence to study procedures. The total study duration is approximately 69 weeks, including screening, treatment, and follow-up periods.

Researchers are evaluating how well the 20-valent pneumococcal conjugate vaccine (20vPnC) protects adults aged 65 and older who are hospitalized with radiologically-confirmed community-acquired pneumonia (RAD+CAP). The study focuses on pneumonia caused by seven new types of the Streptococcus pneumoniae bacteria included in the 20vPnC vaccine. This observational study uses a test-negative design to compare the presence of these specific bacterial types in vaccinated and non-vaccinated participants. Participants provide a urine sample that is tested with BinaxNOW4 S. pneumoniae and serotype-specific urinary antigen detection (UAD) assays to detect the bacteria and its strains. Cases are defined as participants with pneumonia caused by the seven additional serotypes in 20vPnC beyond those in the 13-valent vaccine, plus serotype 15C. Controls include participants without these vaccine serotypes or with pneumonia caused by other agents. The main diagnostic procedure is the non-invasive urine test, and all participants are hospitalized adults aged 65 or older with pneumonia confirmed by chest imaging. Participants share demographic and medical history information and undergo urine testing during their hospital stay, which typically lasts 1 to 2 days for study procedures. Researchers collect data on illness and hospitalization for up to 30 days through medical chart reviews. The primary outcome measures how effective 20vPnC is against pneumonia caused by the additional serotypes over a 55-month period, helping to understand the vaccine's real-world performance in this older population.

Researchers are evaluating the effectiveness of active surveillance and chemotherapy treatments in pediatric, adolescent, and adult patients with low risk and standard risk germ cell tumors. This phase III trial focuses on monitoring patients after tumor removal and comparing the outcomes of carboplatin-based versus cisplatin-based chemotherapy regimens. The study aims to maintain high overall survival rates for low risk patients and to compare event-free survival between the two chemotherapy options in standard risk patients. Additional objectives include assessing side effects such as hearing loss and neuropathy, and exploring tumor marker changes and other biological measures related to treatment outcomes. Patients with low risk stage I germ cell tumors undergo surgery followed by observation, with the option to transfer to standard risk treatment if the tumor recurs. Those with standard risk tumors are randomly assigned to one of four chemotherapy regimens combining bleomycin, etoposide, carboplatin, or cisplatin. Treatments are given intravenously on specific schedules every 21 days for up to 3 or 4 cycles, depending on the group. Throughout the trial, patients receive imaging scans, blood tests, tumor biopsies if needed, and pulmonary function tests to monitor treatment response and side effects. Participants are closely followed after treatment completion with regular visits every 2 months for the first year, then less frequently up to 10 years. Researchers collect data through imaging, blood samples, lung tests, and questionnaires to measure survival, disease recurrence, and side effects like hearing loss. The study also includes exploratory analyses of tumor markers and patient-reported outcomes to better understand treatment impacts and improve future care for germ cell tumor patients.

Researchers are evaluating the addition of nivolumab to the usual treatment of paclitaxel and ramucirumab in patients with advanced or locally unresectable stomach or esophageal adenocarcinoma. This phase II/III trial aims to determine if adding nivolumab improves progression-free survival and overall survival compared to paclitaxel and ramucirumab alone. The study also assesses response rates, disease control, safety, tolerability, and quality of life in participants with PD-L1 CPS 21 1 advanced gastric or esophageal cancer. Participants are randomly assigned to one of two treatment groups. The first group receives nivolumab IV on day 1 of each 28-day cycle, ramucirumab IV on days 1 and 15, and paclitaxel IV on days 1, 8, and 15. The second group receives ramucirumab IV on days 1 and 15 and paclitaxel IV on days 1, 8, and 15 of each cycle. Treatment continues every 28 days until disease progression or unacceptable side effects occur. Optional blood samples may be collected during the study. Imaging with CT and MRI is performed throughout. Participants undergo scans and assessments at baseline and during treatment to monitor cancer progression and treatment effects. They also complete questionnaires on quality of life and symptoms. After treatment ends, participants are followed up at 30, 60, and 90 days and then every 6 months for up to 3 years. Researchers measure progression-free survival and overall survival as primary outcomes, along with other safety and patient-reported measures.

Researchers are evaluating the effects of adding cemiplimab, an immunotherapy drug that blocks the PD-1 pathway to help the immune system attack tumor cells, to the usual treatment of docetaxel and ramucirumab in patients with stage IV or recurrent non-small cell lung cancer. This phase II/III Expanded Lung-MAP trial compares cemiplimab combined with docetaxel and ramucirumab versus docetaxel and ramucirumab alone, aiming to improve treatment outcomes in patients who previously received platinum chemotherapy and immunotherapy but developed resistance or disease progression. Participants are randomly assigned to one of two treatment arms. In Arm I, patients receive dexamethasone orally twice daily on days 0-2, ramucirumab and docetaxel intravenously on day 1 of each 21-day cycle. In Arm II, patients receive the same treatments plus cemiplimab intravenously on day 1 of each cycle. Treatment cycles continue every 21 days until disease progression or unacceptable side effects occur. Throughout the study, patients undergo regular blood sample collection and imaging scans such as CT or MRI to monitor disease status. During the study, participants are closely monitored with scans, blood tests, and physical exams to assess overall survival and other outcomes like progression-free survival, response rates, and treatment safety. Researchers also collect blood samples for future molecular studies. After completing treatment, patients are followed up every 3 to 6 months for up to 3 years to track long-term survival and health status. The study measures overall survival from randomization to death from any cause, assessed up to 3 years.

Researchers are evaluating the safety and effectiveness of apixaban compared with aspirin in patients who recently had an intracerebral hemorrhage (ICH) and also have atrial fibrillation (AF). The study aims to find out if apixaban is better than aspirin in preventing any type of stroke or death from any cause. It also looks at whether apixaban leads to better functional recovery measured by the modified Rankin Scale. This is a phase III, randomized, double-blinded trial enrolling 700 patients over 3.5 years. Participants will be randomly assigned to receive either apixaban, an oral blood thinner that inhibits Factor Xa, or aspirin, an oral antiplatelet medication. The study lasts from 12 months up to 36 months of follow-up after enrollment. Treatments are given orally, and patients will be monitored throughout the study period. Recruitment and coordination occur through NIH/NINDS StrokeNet sites. During the study, participants will undergo assessments including brain imaging (CT or MRI) to confirm diagnosis, functional outcome measurements using the modified Rankin Scale, and monitoring for any strokes or death. Safety will be closely observed, and patients will provide informed consent before joining. The primary outcome measured is stroke or death up to 3 years, and secondary outcomes include functional status changes. Participants are followed regularly to track these outcomes and overall health status.