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 1/2a Open-label Study of VS-7375 a KRAS G12D (ON/OFF) Inhibitor as Monotherapy and in Combination in Patients with Advanced KRAS G12D-Mutant Solid Tumors
VS-7375 is a highly selective oral, non-covalent, small molecule KRAS G12D inhibitor. VS-7375 demonstrated potent inhibition of KRAS G12D-mutated-dependent signal transduction and cancer cell viability in vitro, as well as anticancer activity in human CRC and PDAC xenograft models alone and in combination with cetuximab. Collectively, the significant unmet medical need for treating tumors that harbor KRAS G12D mutations and the nonclinical results with VS-7375 strongly support a rationale for its development in patients with KRAS G12D-mutated cancers.VS-7375 is currently in clinical development in China under the name GFH375 by GenFleet Therapeutics Technology Co., Ltd (Shanghai, China). A first-in-human (FIH) clinical study of VS-7375 (Study GFH375X1101; NCT06500676) is ongoing as a multiphase study in China targeting patients with advanced KRAS G12D-mutated solid tumors, including NSCLC, PDAC, and CRC. The Phase 1 portion of that study involves dose escalation using a Bayesian optimal interval (BOIN) design to evaluate safety, tolerability, and pharmacokinetics (PK) across a range of doses, with initial endpoints focused on evaluating adverse events (AEs) and dose-limiting toxicities (DLTs). As of 17 January 2025, the 750 mg daily dose has been cleared for DLTs, and Study GFH375X1101 remains ongoing in the dose finding stage for patients with KRAS G12D-mutated cancers in China.This study is designed to evaluate the safety, tolerability, preliminary anticancer activity, and PK of VS-7375 in participants with advanced solid tumors harboring a KRAS G12D mutation outside China. The study will be conducted in 4 parts: Part A (single-agent dose escalation),Part B (single-agent dose expansion), Part C (VS-7375 combination dose escalation), and Part D (VS-7375 combination dose expansion).
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
SUNRAY-01 A Global Pivotal Study in Participants with KRAS G12C-Mutant Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing FirstLine Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in those with PD-L1 expression =50% or LY3537982 and Pembrolizumab Pemetrexed Platinum vs Placebo and Pembrolizumab Pemetrexed Platinum regardless of PD-L1 Expression
This study is testing two different treatments (LY3537982 in combination with pembrolizumab against a placebo combined with pembrolizumab) for a cancer called KRAS G12C-mutant NSCLC (non-small cell lung cancer). The study has two parts: Part A compares the treatments with one another for patients whose cancer has a marker called PD-L1 at a level of 50% or higher. Part B looks at the same treatments for patients with PD-L1 ranging from 0 to 100%. The decision about which part a patient joins depends on their doctor and what's best for treatment. Before joining, some patients might get one cycle of regular treatment if they really need it. The study also has two different doses of LY3537982 in combination with pembrolizumab, and they're trying to figure out the best amount, comparing different options to see which one works better. Overall, the study team is hoping to find better treatments for this type of lung cancer.
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.
A Randomized Phase 2 Trial of Fruquintinib and TAS-102 as Compared to Fruquintinib in Patients with Refractory Advanced/Metastatic Microsatellite Stable Colorectal Cancer
This is a Phase 2 study testing whether a combination of TAS-102 and fruquintinib (a selective oral kinase inhibitor) is more effective and safer than fruquintinib alone in patients with advanced colorectal cancer that has spread from its primary location. TAS102 is a chemotherapy medication made of two different drugs that work by interfering with the cell cycle and DNA synthesis in cancer cells, killing the cancer cells. Patients will be randomly divided into two groups. One group will receive the combination of study medicines TAS-102 and fruquintinib, and the other group will receive Fruquintinib alone. Special scans will be done for all patients to check how their tumor size changes in response to the study medicines. Blood samples will be collected for all patients to monitor their overall well-being. The study team will examine and record the time interval for all patients from the start of treatment until their cancer comes back or worsens (progression-free survival). All patients will be closely monitored for potential side effects and safety concerns.