Taki,mie, Japan

Study of Daraxonrasib (RMC-6236) in Previously Treated Patients With RAS Mutated NSCLC (RASolve 301)

This is a global, randomized, open-label, Phase 3 study designed to evaluate whether treatment with daraxonrasib will improve progression free survival (PFS) or overall survival (OS) compared to docetaxel chemotherapy in patients with NSCLC who were previously treated. Patients will be randomized in a 1:1 ratio to receive daraxonrasib or docetaxel chemotherapy.

A Study to Assess the Safety, Tolerability, and Efficacy of NDI-219216 in Patients With Advanced Solid Tumors.

Study 9216-101 is a first-in-human (FIH), Phase 1/2, open-label, dose escalation, dose optimization, and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of NDI-219216 in patients with advanced solid tumors.

Study to Evaluate the Effect of Balcinrenone/Dapagliflozin in Patients With Heart Failure and Impaired Kidney Function

The purpose of this study is to investigate the effect of balcinrenone/dapagliflozin compared with dapagliflozin, on the risk of CV death, HF event with and without hospitalisation, in patients with chronic HF, impaired kidney function, and who have had a recent HF event. Eligible patients will randomly be assigned with a 1:1:1 ratio to receive once daily administration of one capsule and one tablet of one of the following treatments: 1. Balcinrenone/dapagliflozin 15 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet 2. Balcinrenone/dapagliflozin 40 mg/10 mg capsule and matching placebo for dapagliflozin 10 mg tablet 3. Dapagliflozin 10 mg tablet and matching placebo for balcinrenone/dapagliflozin capsule The study is event driven, and the average study duration for a participant is estimated to be 22 months including screening period, 20 months blinded treatment period and a one-month follow-up period on open-label dapagliflozin. The study will be conducted at approximately 700 sites in approximately 40 countries globally.

The PLATINUM Trial: Optimizing Chemotherapy for the Second-Line Treatment of Metastatic BRCA1/2 or PALB2-Associated Metastatic Pancreatic Cancer

PRIMARY OBJECTIVES: I. To evaluate and compare overall response rate (ORR) in patients with BRCA1/2 or PALB2 mutant pancreas cancer whose disease has progressed on front-line fluorouracil, irinotecan, leucovorin and oxaliplatin (FOLFIRINOX) treated with nab-paclitaxel, gemcitabine, and cisplatin (NABPLAGEM) = nab-paclitaxel, gemcitabine, and cisplatin (arm 1) versus nab-paclitaxel and gemcitabine (arm 2). (Phase II) II. To evaluate and compare overall survival (OS) time in patients with BRCA1/2 or PALB2 mutant whose disease has progressed on front-line FOLFIRINOX treated with 1) NABPLAGEM = nab-paclitaxel, gemcitabine, and cisplatin (arm 1) versus nab-paclitaxel and gemcitabine (arm 2). (Phase III) SECONDARY OBJECTIVES: I. To evaluate and compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) criteria between 2 treatment arms. II. To evaluate and compare duration of response (DoR) between 2 treatment arms. III. To evaluate and compare CA19-9 response (defined as patients with a baseline CA19-9 >= 2x upper limit of normal (ULN) who demonstrate a minimum 25% decrease in CA19-9 at any time point) between 2 treatment arms. IV. To evaluate and compare toxicity profile as assessed by treating clinicians between 2 treatment arms. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive nab-paclitaxel intravenously (IV) over 30-40 minutes, gemcitabine IV over 30-40 minutes, and cisplatin IV over 30-60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) or computed tomography (CT) throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study. ARM II: Patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI or CT throughout the trial. Patients may optionally undergo blood sample collection at baseline and on study. After completion of study treatment, patients are followed up within 30 days and then every 3 months for 2 years or until death, whichever comes first.

TEMPUS ARIES: A Biobank Registry Platform Study in Oncology

A Study of Sigvotatug Vedotin Versus Docetaxel in Previously Treated Non-small Cell Lung Cancer

AS-1763 in Patients With Previously Treated CLL/SLL or Non-Hodgkin Lymphoma

This study consists of 2 parts. Dose escalation part will enroll up to 27 patients to evaluate safety profile and tolerance of docirbrutinib using 3+3 design. The starting dose of docirbrutinib in oral tablet form is 100 mg twice daily (200 mg/day). Dose escalation will continue up to the planned maximum dose level or until the maximum tolerated dose (MTD) has been identified. Dose expansion part will enroll up to 48 CLL/SLL patients (Cohort 1), up to 35 NHL patients (Cohort 2), and up to 10 patients with prior pirtobrutinib treatment for an approved indication (Cohort 3). The first 30 patients in each Cohort 1 or 2 will be allocated to three dose levels (n=10 at each dose level) which will be selected based on the data from dose escalation. Preliminary efficacy and safety data from the first 30 patients in one of cohorts will be used to identify the provisional recommended Phase 2 dose (RP2D) level. Thereafter, up to a further 18 patients for Cohort 1 and up to a further 5 patients for Cohort 2 will be enrolled and allocated to the provisional RP2D level. Cohort 3 will be enrolled in parallel with Cohorts 1 and 2 and will be allocated to up to two dose levels (either n=10 at a single dose level or n=5 at each of 2 dose levels). Study assessments will continue for 24 cycles (1 cycle = 28 days) or until disease progression, occurrence of unacceptable toxicity, or discontinuation because of other reasons. Patients will then be followed for survival status for a further 2 years. RP2D will be determined based on all the data generated in the study.

mFOLFIRINOX Versus mFOLFOX With or Without Nivolumab for the Treatment of Advanced, Unresectable, or Metastatic HER2 Negative Esophageal, Gastroesophageal Junction, and Gastric Adenocarcinoma

PRIMARY OBJECTIVE: I. To determine if overall survival (OS) is improved in patients who received mFOLFIRINOX +/- nivolumab in comparison to FOLFOX +/- nivolumab as first-line chemotherapy for metastatic gastroesophageal adenocarcinoma. SECONDARY OBJECTIVES: I. To compare other indices of efficacy, including progression-free survival, objective response rates and duration of response between both treatment arms. II. To evaluate safety and tolerability associated with treatment in each of the treatment arms. III. To evaluate the proportion of patients receiving second line of therapy in both arms. IV. To evaluate tolerability of the treatment in both arms using Patient Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE). EXPLORATORY OBJECTIVES: I. Exploratory correlative markers will also be measured and evaluated within and between arms to better assess mechanisms and prognostic impact of markers on impact. These will include baseline PD-L1 combined positive score (CPS) and cell free deoxyribonucleic acid (cfDNA) before and after treatment. II. To evaluate and assess the feasibility and compliance associated with not centrally collecting perceived attribution of protocol treatment to reported adverse events. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive fluorouracil intravenously (IV), leucovorin calcium IV, oxaliplatin IV, and irinotecan IV on study and nivolumab IV as clinically indicated. Patients undergo magnetic resonance imaging (MRI) and a computed tomography (CT) scan throughout the trial. Patients may also undergo blood sample collection on study. ARM II: Patients receive fluorouracil IV, leucovorin calcium IV, and oxaliplatin IV on study and nivolumab IV as clinically indicated. Patients undergo MRI and a CT scan throughout the trial. Patients may also undergo blood sample collection on study.

A Study to Investigate the Efficacy of Durvalumab Plus Tremelimumab in Combination With Chemotherapy Compared With Pembrolizumab in Combination With Chemotherapy in Metastatic NSCLC Patients With Non-squamous Histology Who Have Mutations and/or Co-mutations in STK11, KEAP1, or KRAS

A trial to learn if durvalumab plus tremelimumab with chemotherapy is safe and how well it works compared to pembrolizumab with chemotherapy in participants with metastatic non-small cell lung cancer with certain genetic mutations. INFORMATION FOR TRIAL PARTICIPANTS: Researchers are looking for a better way to treat people who have metastatic NSCLC and tumors with STK11, KEAP1, or KRAS genetic mutations. Most people learn they have NSCLC after it has already become metastatic, and it can no longer be treated with surgery. Based on previous trials, researchers think durvalumab plus tremelimumab with chemotherapy could help participants more than the current standard treatment, which is pembrolizumab with chemotherapy. Durvalumab and tremelimumab are designed to work by helping the immune system recognize and kill cancer cells. In this trial, researchers want to learn more about how well durvalumab plus tremelimumab with chemotherapy works in people with metastatic NSCLC and genetic mutations that can cause the cancer to be less responsive to treatment. This trial is planned to have 280 participants. These participants will be randomly divided into one of two groups: - One group will receive durvalumab plus tremelimumab with standard of care chemotherapy - One group will receive pembrolizumab with standard of care chemotherapy Durvalumab, tremelimumab, pembrolizumab, and chemotherapy are given as an injection over time into a vein, also called an IV infusion. Chemotherapy will be one of the following regimens: pemetrexed plus cisplatin or pemetrexed plus carboplatin. This is an open-label trial. This means that each participant will know which trial treatment they receive, and the doctors and trial staff will also know. Researchers will measure and compare: - How long participants live during the trial - How long participants live during the trial without their cancer getting worse - How many participants' tumors respond to treatment - How long participants' tumor responses last - How long before participants need to start a different treatment type Researchers will also keep track of all the medical problems participants have during the trial and monitor their safety. Participants will stop receiving trial treatment if they no longer benefit from it or they stop participating for another reason. Participants will visit their trial site every 3 to 4 weeks. At most visits, participants will: - Have a physical exam and answer questions about any medications they are taking or any medical problems they have - Receive their trial treatment - Give blood and urine samples - Have pictures of their tumors taken using CT or MRI scans

Stepped Approach to Reducing Risk of Suicide in Primary Care

This five-year multi-site study consists of the following essential elements: (1) recruitment of 2,572 adolescents ages 12-17 years inclusive at baseline, and their parent/guardian; (2) initial assessment of youth and parent/guardian participants using direct interviews and standardized questionnaires; and (3) follow-up assessments of all participants at 3-months, 6-months, and 1-year post-baseline. To achieve the study objectives, the project will be conducted in 14 pediatric primary care practices. The study consists of three phases of data collection: TAU, intervention, and sustainability. Eight hundred forty-nine suicidal youth will be enrolled during the TAU phase, and 1,723 suicidal youth will be enrolled during the intervention phase (total number of youth participants = 2,572). Youth and parent participants enrolled in the study will complete multiple questionnaires at four time points (baseline, 3-months, 6-months, and 12-months). Medical record reviews of youth participant files will occur throughout the study and be reviewed by research staff. The intervention phase is followed by a 6-month sustainability phase during which the participating practices will work on maintaining or further improving upon the anticipated gains made during the intervention phase. Phase 1: TAU TAU immediately precedes the intervention phase and ranges in length from 6 to 26 months. During TAU, participants will be treated according to usual and customary care, thus establishing each site's baseline rate of suicide risk screening and detection. Usual care at each participating practice involves screening for depression and suicide risk with the PHQ-9. This baseline rate will serve as the control for subsequent study phases. Phase 2: Intervention The intervention phase will range from 11 to 30 months. During this phase, each site will implement the clinical pathway, which includes universal screening for suicide risk using the Ask Suicide-Screening Questions (ASQ), a four-item questionnaire. Those who screen positive will then be evaluated using the Brief Suicide Safety Assessment (BSSA). The BSSA allows the clinician to assess the level of suicide risk to then choose how to proceed with clinical next steps. Clinicians will triage care based on three categories of risk: low-risk, further evaluation needed, and imminent-risk. The risk assessment will determine the type of care the individual then receives (e.g., mental health referrals, mental health evaluation and safety plan, tele-psychiatry crisis intervention consultation, send to ED). We will also conduct in-depth qualitative interviews with a purposive sample of providers (e.g., physicians, nurses, social workers) at each of the participating sites. Purposive sampling is a way to identify and recruit participants that are especially experienced with or knowledgeable about a phenomenon of interest. Provider participants will complete a series of questionnaires at three separate times: 1) prior to clinical pathway training, 2) after training, and 3) 6 months after training. Provider participants will also be trained on the quality improvement process for implementing the intervention strategy. Some provider participants will be asked to complete up to four qualitative interviews that will focus on the implementation process, barriers and facilitators to successful implementation of the clinical pathway, and lessons learned. Phase 3: Sustainability The intervention phase is followed by a 6-month sustainability phase during which the site will work on maintaining or further improving upon the anticipated gains made during the intervention phase. No participants will be recruited during the sustainability phase and this phase will not be used to evaluate intervention effectiveness. The specific aims include: Aim 1: To implement, study, and improve through a Plan-Do-Study-Act (PDSA) cycle, the STARRS-PC intervention that includes suicide risk detection, assessment and triage, and care management based on risk profile. PDSA is a systematic way to test a change that is implemented by breaking down the implementation process into specific steps, and then evaluating the outcome, improving on it, and testing again. Aim 2: Test the effectiveness of STARRS-PC compared to TAU on the primary patient outcome, suicide attempts, secondary patient outcomes (suicidal ideation, non-suicidal self-injury (NSSI), and family satisfaction) at 12 months post-baseline, as well as mediators and moderators, through a stepped wedge design. - Hypotheses: STARRS-PC will significantly reduce the rate of: 1) suicide attempts (nonfatal and fatal) and 2) suicidal ideation, NSSI, and improve family satisfaction during the 12-month post-baseline follow-up period compared with TAU. - Exploratory Aim 2a: To examine whether increases in provider knowledge, self-efficacy, and buy-in regarding suicide risk screening, assessment, and management will mediate the intervention effect on patient outcomes. - Exploratory Aim 2b: To examine whether organization readiness and practice integration will moderate effects of intervention on patient outcomes. Aim 3: To identify barriers to and facilitators of implementation and sustainability of an intervention designed to improve suicide risk detection and risk management using qualitative interviews and surveys with clinical stakeholders at each study site.