A Phase 1/2 Open-Label Multi-Center First-in-Human Study of the Safety Tolerability Pharmacokinetics and Anti-Tumor Activity of TPX-0005 in Patients with Advanced Solid Tumors Harboring ALK ROS1 or NTRK1-3 Rearrangements (TRIDENT-1)
Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction. (*site is not participating in the sub-study)Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.
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 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.
A Phase 1/2 Study to Evaluate the Safety and Efficacy of MK-2870 Monotherapy or in Combination With Other Anticancer Agents in Gastrointestinal Cancers
This study is testing a new cancer treatment called MK-2870 to see if it has few side effects and works well for patients with certain types of gastrointestinal (GI) cancers. Patients will join the study and be placed into one of three groups based on their type of cancer: patients with colorectal cancer (CRC), patients with pancreatic cancer (PDAC), and patients withbiliary tract cancer (BTC). The study will check for side effects and see how well the treatment helps shrink tumors. For the CRC group, the study will first test the safety and side effects of MK-2870 with another drug, a combination of 5-FU (5-fluorouracil) and LV (leucovorin), before moving on to see how well it works. Any side effects will be carefully tracked and reported.
A Phase 1/2 Study to Evaluate the Safety and Efficacy of Patritumab Deruxtecan (MK-1022) in Gastrointestinal Cancers
This is a Phase 1/2 study testing a new medicine HER3-DXd, also known as Patritumab Deruxtecan (antibody drug conjugate), in patients with Gastrointestinal cancers that have spread to other parts of the body. Patients will be divided into three groups based on their type of cancer. Group 1 will enroll patients with Colorectal cancer. Group 2 will enroll patients with Biliary tract cancer. Both these groups of patients will receive HER3-DXd medicine at a single dose level. Group 3 will enroll liver cancer (Hepatocellular carcinoma) patients who will be divided to receive different dose levels of the study medicine to find out the dose that works well and has fewer side effects. The study team will collect blood samples from all patients to see how their bodies are processing the study medicine and if they are doing well. Special scans will be taken from all patients to see how the tumor is responding to the study medication. Study doctors will perform genetic testing (biomarkers) on blood and tissue samples in the hope of further helping patients. All patients will be closely monitored for side effects and any safety concerns.
A Phase 1/2a Multicenter Open-Label First in Human Study to Assess the Safety Tolerability Pharmacokinetics and Preliminary Antitumor Activity of DB-1303 in Patients with Advanced/Metastatic Solid Tumors
This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303 in subjects with advanced solid tumors that express HER2.
A Phase 1/2a Multicenter Open-Label First in Human Study to Assess the Safety Tolerability Pharmacokinetics and Preliminary Antitumor Activity of DB-1305 in Subjects with Advanced/Metastatic Solid Tumors
This is a multicenter, non-randomized, open-label, multiple-dose, first in human (FIH) study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D); Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic malignant solid tumors.
A Phase 1a/1b First-in-human Multicenter Study to Assess the Efficacy and Safety of RGT-61159 for Treatment of Patients with Relapsed/Refractory Adenoid Cystic Carcinoma (ACC) or Colorectal Carcinoma (CRC)
This study will test the potential tumor-fighting effects of a daily medication called RGT-61159 for patients with advanced ACC or CRC, two types of cancer, when other treatments have stopped working or aren’t suitable. Patients will take RGT-61159 in 21-day cycles, starting at a dose of 6 mg. The study uses a dose-escalation plan, meaning patients will move to higher doses until the highest safe dose, or recommended Phase 2 dose (RP2D), is found. If certain side effects appear, more patients may be added at the current dose level to carefully check for safety and find the best dose for future studies.
A Phase 1a/1b Open-Label Study Evaluating the Safety Tolerability Pharmacokinetics and Efficacy of BBO-8520 in Subjects with Advanced KRASG12C Mutant Non-Small Cell Lung Cancer - the ONKORAS-101 Study
This is a Phase 1 study testing whether the new medicine BBO-8520 (a KRASG12C on/off inhibitor) is a safe and effective treatment option if given alone or together with another medicine called pembrolizumab (immunotherapy) for lung cancer patients whose tumors show changes in the KRAS gene. The study consist of two parts. In part 1, patients will be enrolled into one of five groups to receive the study medicine BBO-8520 alone. The study team will gradually increase the dose level of the study medicine for each group to find out the effective dose with fewer side effects. Some patients will be grouped to receive study medicine BBO-8520 together with pembrolizumab. In part 2, more patients will be included to receive the dose that was found to be effective while being safe. Patients who have previously received approved KRAS G12C inhibitors (ie, sotorasib and adagrasib) will be eligible. All patients will have blood samples taken to see how their bodies are handling the study medicines. The study team will have imaging scans taken for all patients to see how the study medicine is changing their tumor size. All patients will be closely monitored for side effects and safety concerns.