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.
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 1/2a 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.
A Phase 1a/1b Trial of LY3962673 in Participants with KRAS G12D-Mutant Solid Tumors
This study is testing the tolerability, effectiveness, and potential for few side effects of the drug LY3962673 in patients with advanced solid tumors that have a KRAS G12D mutation, like pancreatic, colorectal, and lung cancer. In Phase 1a, the drug will be tested alone to see if it is well-tolerated and has few side effects. Some patients may receive different doses to check for side effects and how the drug works in the body. In Phase 1b, LY3962673 will be tested alone and with other standard treatments to find the best dose for these cancers. A committee will decide on dose increases based on the safety data.