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 Randomized Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer
This is a phase 3 study testing and comparing if study medicine amivantamab (monoclonal antibody) in combination with mFOLFOX6 or FOLFIRI (chemotherapy) is more beneficial than another medicine called cetuximab (Monoclonal antibody) in combination with mFOLFOX6 or FOLFIRI for patients whose colorectal cancer has spread from the primary location and that the tumor has KRAS/NRAS and BRAF wild-type genes. Patients will be divided into two groups. One group will receive amivantamab together with mFOLFOX6 or FOLFIRI, and the other group will receive cetuximab and mFOLFOX6 or FOLFIRI. All participants will have special scans taken to see if the study treatment is changing their tumor size and that the cancer is not progressing. The study team will collect blood samples from all patients to see how their bodies are responding to these medicines and whether antibodies to the study medicine are formed. Genetic testing will be done on blood and tumor samples in the hope of further helping patients. All patients will be monitored for side effects and safety throughout the study.
A Randomized Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wildtype Recurrent Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy
This is a randomized, open-label, active-controlled, parallel-group, multicenter, interventional, Phase 3 study of amivantamab and FOLFIRI compared with cetuximab or bevacizumab (investigator’s choice) and FOLFIRI in participants who have recurrent, unresectable or metastatic CRC that is KRAS/NRAS and BRAF WT.Participants must have received and radiographically progressed on or after fluoropyrimidine- and oxaliplatin-based chemotherapy, with or without anti-VEGF treatment, and must not have received prior irinotecan-based chemotherapy in the metastatic setting, anti-EGFR therapy, or anti-MET therapy.The screening period will be up to 28 days prior to randomization. The treatment period will begin on Cycle 1 Day 1 and continue as 28-day cycles. Participants will receive study treatment until radiographic disease progression by BICR or other discontinuation criteria are met. Participants will then be followed for survival, subsequent anticancer treatment, and disease status. Participant safety and study conduct will be monitored throughout the study.Following the final analysis of OS, participants who continue to benefit from study treatment, as determined by the investigator, may continue to receive access to study treatment(s), either via an open-label or long-term extension rollover study or any other post-trial access program, when available and permitted by local regulations.
A Phase 1/1b Open-label Multicenter Study to Investigate the Safety Tolerability Pharmacokinetics and Antitumor Activity of KIN-2787 in Participants with BRAF and/or NRAS Mutation-positive Solid Tumors
This is a 2-part, open-label, multicenter, dose escalation and dose expansion study in participants with rapidly accelerated fibrosarcoma, homolog B (BRAF) mutation-positive and/or neuroblastoma RAS (NRAS) mutation-positive tumors designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of KIN-2787, a pan-rapidly accelerated fibrosarcoma (RAF) small molecule kinase inhibitor; to determine a recommended Phase 2 dose (RP2D) of KIN-2787 for further clinical development; and to assess the objective response to KIN-2787 therapy alone and in combination with binimetinib, a mitogen-activated protein kinase (MEK) inhibitor.
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 Ib/II Open-Label Multicenter Study Evaluating the Safety Activity And Pharmacokinetics of Divarasib in Combination with Other Anti-Cancer Therapies in Patients with Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer with a KRAS G12C Mutation
A Phase Ib/II, Open-Label, Multicenter Study Evaluating the Safety, Activity, And Pharmacokinetics of Divarasib in Combination with Other Anti-Cancer Therapies in Patients with Previously Untreated Advanced or Metastatic Non-Small Cell Lung Cancer with a KRAS G12C Mutation
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.
A Phase 1b Study to Evaluate the Safety Tolerability and Preliminary Efficacy of ATP150/ATP152 VSV-GP154 and Ezabenlimab (BI 754091) in Patients with KRAS G12D/G12V Mutated Pancreatic Ductal Adenocarcinoma
This is an open-label, phase 1b study comprising two parts (safety and immunogenicity part and randomized efficacy part) to evaluate the safety, tolerability, preliminary efficacy, and immunogenicity of a heterologous prime-boost vaccine (protein and viral vector) strategy, in which approximately 90 patients with resected KRAS G12D/G12V mutated pancreatic cancer and colorectal cancer after (neo-) adjuvant chemotherapy or chemoradiotherapy will be enrolled in the following treatment parts of the study:Part 1 (Safety and Immunogenicity Part) – PDAC and CRC patientsPart 2 (Efficacy Part) – PDAC patients only
An Open-label Phase 1 Multicenter Study to Evaluate the Safety and Preliminary Anti-tumor activity of NT-112 in Human Leukocyte Antigen-C*08:02-Positive Adult Subjects with Unresectable Advanced and/or Metastatic Solid Tumors That Are Positive for the KRAS G12D Mutation
This study is testing a NT-112, a type of cellular therapy, in patients with advanced cancer, such as lung, pancreatic, or colorectal cancer, who have a specific genetic change called KRAS G12D. The study team wants to see if the medicine has few side effects and is effective in treating the cancer. They will try different amounts of the medicine to find thehighest dose that patients can handle without severe side effects. The researchers will carefully follow a plan to decide how much medicine each patient will get. The study team will keep a close eye on any side effects. The study has different periods, like screening, where they check if people meet the criteria, enrollment, treatment, and follow-up. Patients will go through various tests before joining the study, and the researchers will collect information about safety, effectiveness, and other factors.
Dafna Bar-Sagi, PhD | NYU Langone Health
Dafna Bar-Sagi, PhD, is executive vice president and vice dean for science, chief scientific officer of NYU Langone and a professor of biochemistry.