A Phase 1/1b Study of ASP2138 in Participants With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma or Metastatic Pancreatic Adenocarcinoma Whose Tumors Have Claudin (CLDN) 18.2 Expression
Claudin 18.2 protein, or CLDN18.2 is a protein found on cells in the digestive system. It is also found on some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to 2 targets at the same time: CLDN18.2 and a protein called CD3 found on immune cells, called T-cells. ASP2138 works by binding to both the tumor cell and CD3 which "tells" the immune system to attack the tumor.ASP2138 is a potential new treatment for people with stomach cancer, gastroesophageal junction cancer, (cancer where the tube that carries food (esophagus) joins the stomach) or pancreatic cancer. Before ASP2138 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This information will help to find a suitable dose and to check for potential medical problems from the treatment.Adults 18 years or older with stomach cancer, gastroesophageal junction cancer, or pancreatic cancer can take part. Their cancer is locally advanced unresectable or metastatic. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body.The main aims of the study are to check the safety of ASP2138, how well it is tolerated, and to find a suitable dose of ASP2138 to be used later in this study.This is an open-label study. This means that people in this study and clinic staff will know that people will receive ASP2138.The study will have 2 phases. In phase 1, different small groups of people will receive lower to higher doses of ASP2138. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP2138 to use later in the study. The first group will receive the lowest dose of ASP2138. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP2138. The panel will do this for each group until all groups have received ASP2138, or until suitable doses have been selected for later in the study. Doctors will also check how each type of cancer is responding to ASP2138.In phase 1b, other different small groups will receive suitable doses of ASP2138 found from phase 1. This phase will check how each type of cancer responds to ASP2138. The response to ASP2138 is measured using scans and blood tests. Doctors will continue to check all medical problems throughout the study.ASP2138 will be given through a vein in the arm. This is called an infusion. People will receive weekly infusions of ASP2138 in a 14-day (2-week) treatment cycle. People will continue to receive treatment until: their cancer gets worse; they have medical problems they can't tolerate; they ask to stop treatment; the doctors decide that continuing treatment is no longer in that person's best interest; the study is ended by the sponsor. Doctors will check if people had any medical problems from ASP2138. Other checks will include medical examinations, checking the nervous system, blood and urine tests and vital signs. Nervous system checks include checking peoples state of mind, reflexes, balance, movement and muscle strength. Vital signs include medical examinations, body temperature, breathing rate, and blood oxygen levels. Electrocardiograms (ECG) will be done to check the heart rhythm during the study. People will receive ASP2138 in a hospital. They will have blood tests and doctors will check for medical problems. People will also visit the clinic on certain days during their treatment, with extra visits during the first 3 cycles of treatment.People will visit the clinic after treatment has finished. The doctors will check for more medical problems. Other checks will include medical examinations, blood and urine tests, and vital signs. People will also have an ECG.After this, people will visit the clinic for a check-up several times. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their treatment or not.
A Phase 1/2 First-Time-in-Human open-label multicenter dose escalation and expansion study of the oral DNA Helicase Werner Inhibitor (WRNi) GSK4418959 alone or in combination with other anti-cancer agents in adult participants with Mismatch Repair-deficient (dMMR) or Microsatellite Instability-High (MSI-H) solid tumors (SYLVER)
This study will test how well the oral WRN inhibitor GSK4418959 works and whether it has few side effects, both by itself and with dostarlimab, in patients with advanced cancers that have specific genetic markers called dMMR/MSI-H, including colorectal and endometrial cancer. First, patients will go through a pre-screening process to check if their tumors have these markers and see if they qualify. Those who qualify will join one of three parts of the study: Part 1 will test different doses of GSK4418959 alone in patients with advanced tumors; Part 2 will use the best dose from Part 1 to test the drug in patients with advanced colorectal or endometrial cancer; and Part 3 will test different doses of GSK4418959 combined with dostarlimab in patients with advanced tumors.
A Phase 1/2 Multicenter Open-Label Study to Evaluate the Safety Tolerability and Preliminary Antitumor Activity of TNG456 Monotherapy and in Combination with Abemaciclib in Patients with Solid Tumors with MTAP Loss
This study is testing a new medicine, TNG456, alone and with another medicine called Abemaciclib, to find the dose that works well and has fewer side effects for patients with solid tumors with loss of the MTAP gene or MTAP protein who have tried other standard treatments before. This study has two parts. In the first part, the study team will find out the most effective dose of TNG456 with fewer side effects by testing different doses of the study medicine. The doctors will gradually increase the dose of TNG456 while looking closely for the side effects. In the second part, more patients will be included to get the most effective dose found in the first part of the study. All patients will have their blood samples taken to see how they are doing and how their bodies are handling the medicine. The patients will have special scans taken at different times throughout the study. The doctors will evaluate the results and outcomes to learn how the medicine changes the tumor. All the patients will be closely monitored for discomfort and side effects throughout the study.
A Phase 1/2 Multicenter Open-Label Study to Evaluate the Safety Tolerability and Preliminary Antitumor Activity of TNG462 in Combination with Other Agents in Patients with Pancreatic or Non-Small Cell Lung Cancer with MTAP Loss and RAS Mutation
This Phase 1/2 study will determine the safety, tolerability, PK, PD, and preliminary antineoplastic activity of oral TNG462 in combination with RMC-6236 or RMC-9805.Overall, the study comprises a dose escalation phase and a dose expansion phase.
A Phase 1/2 Multiple Expansion Cohort Trial of MRTX1719 in Patients with Advanced Solid Tumors with Homozygous MTAP Deletion
This study is testing the effectiveness of a new drug, MRTX1719, in patients with advanced solid tumors that have a specific genetic change called MTAP deletion. The study follows guidelines from the U.S. Food and Drug Administration (FDA). The study starts with Phase 1, which will test different doses of MRTX1719 to find the most effective one with less sideeffects. In Phase 2, MRTX1719 will be tested in different groups of patients based on their type of cancer and other characteristics to see how well the drug works and how safe it is. There are plans to make changes during the study to prepare for future tests, depending on the results. The study includes careful monitoring, genetic testing to confirm eligibility, andregular checks on how the drug affects the patients.
A Phase 1/2 Open-Label Study to Evaluate the Safety Tolerability Pharmacokinetics and Efficacy of TNG260 as Single Agent and in Combination with an anti-PD-1 Antibody in Patients with STK11-Mutated Advanced Solid Tumors
This is a first-in-human Phase 1/2, open-label, multicenter, dose-escalation and -expansionstudy designed to determine the MTD of TNG260 as single agent and in combination withpembrolizumab, to determine the RP2D(s) of the combination, and to evaluate the safety andtolerability, PK, and antineoplastic activity of escalating oral doses of TNG260 whenadministered alone and with a standard dose of pembrolizumab in participants with locallyadvanced or metastatic STK11-mutated solid tumors who have progressed on at least 1 lineof standard therapy or are ineligible for standard therapies.In Phase 1 (dose escalation), at least 3 DLT-evaluable participants will be enrolled insequentially escalating dose cohorts to determine the MTD of single agent TNG260, theMTD of the combination of TNG260 and pembrolizumab, and the RP2D(s) of TNG260 incombination with a standard dose of pembrolizumab. The dose escalation of TNG260 will beguided by two BLRMs based on any DLTs observed in the first cycle (ie, the first 21 days) ofthe single agent therapy and the second cycle for the combination therapy.Participants in Phase 2 (dose expansion) will be dosed at the RP2D(s) determined fromPhase 1 based on demonstrated tolerability, together with available PK data and results oftarget engagement studied during Phase 1 (or other measures including PD and efficacy), asapplicable. Three Phase 2 combination expansion arms (TNG260 in combination withpembrolizumab) will enroll up to approximately 30 participants each.
A Phase 1/2 Study of LY3537982 in Patients with KRAS G12C-Mutant Advanced Solid Tumors
Study LOXO-RAS-20001 is a first-in-human, multicenter, open-label Phase 1/2 study to evaluate the safety, tolerability, and preliminary efficacy of oral LY3537982 as monotherapy and as part of combination therapy in patients with KRAS G12C-mutant advanced solid tumor types, including but not limited to NSCLC and CRC.This study includes 2 parts, Phase 1a dose escalation (Part A) followed by a Phase 1b dose expansion (Part B-E). The Phase 1a dose escalation LY3537982 monotherapy cohort will enroll any eligible patient with KRAS G12C-mutant advanced solid tumor. Once the LY3537982 monotherapy RP2D (RP2DM) is established, Phase 1b dose expansion will begin and include 10 cohorts (NSCLC, Cohorts B1–B6; CRC, Cohorts C1–C2; other solid tumors [except NSCLC and CRC], Cohort D1; KRAS G12C-mutant advanced NSCLC who have previously been treated with a KRAS G12C inhibitor, Cohort E1) to further evaluate safety and clinical activity.KRAS G12C mutations will be identified through standard of care testing as routinely performed at each participating site utilizing material collected prior to patient consent to this protocol. Molecular assays utilized for enrollment are required to be performed in Clinical Laboratory Improvement Amendments (CLIA), International Organization for Standardization/International Electrotechnical Commission (ISO/IEC), College of American Pathologists (CAP), or other in a similarly certified laboratory.
A PHASE 1/2 STUDY OF REGN5678 (ANTI-PSMAXCD28) WITH OR WITHOUT CEMIPLIMAB (ANTI-PD-1) IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER AND OTHER TUMORS ASSOCIATED WITH PSMA EXPRESSION
This is an open-label, phase 1/2, first-in-human (FIH) study evaluating safety, tolerability, PK, and anti-tumor activity of REGN5678 (anti- PSMAxCD28) alone and in combination with cemiplimab (anti-PD-1) in treatment-experienced metastatic castration-resistant prostate cancer (mCRPC).There are two parts of the study:? Dose escalation: During dose escalation, patients will receive a 3- week monotherapy lead-in of REGN5678 at the assigned dose level (DL) administered intravenously (IV) weekly (QW) followed by combination therapy of REGN5678 at the assigned DL IV QW and cemiplimab 350 mg IV every 3 weeks (Q3W).? Dose Expansion: During dose expansion, patients will receive combination therapy of REGN5678 at the assigned DL (eg, maximum tolerated dose [MTD]/recommended phase 2 dose [RP2D]) IV QW and cemiplimab 350 mg IV Q3W without a 3- week monotherapy lead-in of REGN5678.Dose expansion cohort(s) will be enrolled after identification of the REGN5678 MTD in combination with cemiplimab and/or RP2D. Prior to enrollment of an expansion cohort, 3 to 6 additional patients will be enrolled at that DL without a 3-week monotherapy lead-in of REGN5678 to further evaluate safety and biologic activity (dose escalation cohorts designated with an asterisk [*cohorts]).Safety evaluations will be conducted at each study drug dosing visit. Radiographic response assessment will be performed every 6 weeks from cycle 1 (C1D42/C2D1) up to cycle 4 (including patients who receive the initial 3-week monotherapy lead-in of REGN5678) and every 12 weeks thereafter.Investigators should continue treating patients with study drug until confirmed disease progression, elective discontinuation for response, per modified PCWG3, intolerable adverse events (AEs), withdrawal of consent, or other study withdrawal criterion is met. Patients who do not withdraw consent will then be expected to continue off-treatment follow-up procedures.
A Phase 1/2 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 in Patients with Advanced NSCLC and Other Solid Tumors (ALKOVE-1)
A Phase 1/2 Study of the Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor NVL-655 in Patients with Advanced NSCLC and Other Solid Tumors (ALKOVE-1)
A Phase 1/2 Study to Evaluate the Safety and Efficacy of AZD0486 in Adolescent and Adult Participants with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia
This study is designed to test how effective a new drug called AZD0486 (BITE for CD19) is for patients relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) who have already tried at least 1-2 other treatments. This study has three parts: Part A will test increasing doses of AZD0486 to find a dose with few side effects; Part B will test up to two doses from Part A to decide the best dose to use in the next phase; and Part C will use the best dose from Part B to see how well it works in more patients. AZD0486 will be given as an IV infusion on certain days of each 28-day cycle, with close monitoring for side effects. Side effects and effectiveness will be checked regularly, and the study will continue untilenough data is collected to understand how well AZD0486 works and how safe it is.