Tests GNS561 with trametinib in advanced KRAS-mutated bile duct cancer

Trial details

Who runs it

Genfit

Trial code

NCT05874414

Record updated

13 July 2026

Original description

This is an open-label, multicenter Phase 1b/2a study to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of GNS561 in combination with trametinib in Advanced KRAS Mutated Cholangiocarcinoma after failure of standard-of-care first line therapyRead full original descriptionShow less

Phase 1b/2a Study of GNS561 in Combination With Trametinib in Advanced KRAS Mutated Cholangiocarcinoma

This is an open-label, multicenter Phase 1b/2a study to evaluate safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of GNS561 in combination with trametinib in Advanced KRAS Mutated Cholangiocarcinoma after failure of standard-of-care first line therapy

Inclusion: Histologically confirmed intrahepatic CCA with a documented KRAS mutation; Patients greater than or equal to 18 years of age; Patients must have disease progression that is not amenable to potentially curative treatment; Patients must have received one or two lines of chemotherapy; Patients must have at least one measurable disease by RECIST v1.1; Performance status (ECOG) 0-1; Adequate organ baseline function defined as follows: absolute neutrophil count ≥1000 cells/μL, platelet count ≥75,000 cells/μL, hemoglobin ≥9 g/dL, aspartate aminotransferase or alanine aminotransferase less than or equal to 3 × upper limit of normal, estimated glomerular filtration rate ≥60 mL/min, corrected QT interval by Fridericia's (QTcF) interval ≤470 msec; Women of childbearing potential must present with a negative serum pregnancy test and agree to use adequate contraception during the study and until 6 months after the end of treatment. Male patients with women partners of childbearing potential must agree with the contraception procedures of the study protocol; Patients must be able to understand and be willing to comply with the requirements of the study protocol; Patients participate voluntarily and sign informed consent form(s).

Exclusion: Previous treatment with a MEK inhibitor or autophagy inhibitor; Previous treatment with three or more lines of prior chemotherapy; Patients who have not recovered for certain AEs due to previous lines of therpay; Extrahepatic CCA with recent (within 6 weeks) placement of a stent or episodes of unstable biliary stents (manifest as obstruction, migration of the stent, infevtion or mechanical failure of the stent) within 6 weeks according to investigator's judgement; Known active viral hepatitis, including HBV and HCV; Patients with known allergic reaction to quinoline derivatives (e.g., quinine, chloroquine, mefloquine) and/or hypersensitivity to study drugs; Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:; Cardiovascular disorders: congestive heart failure New York Heart Association ≥ class 2 or left ventricular ejection fraction (LVEF) <50%, arrythmias or cardiac conduction abnormalities. Uncontrolled arterial hypertension or inadequately controlled arterial hypertension, at the discretion of the investigator, based on an average of = >3 BP readings over = >2 sessions; Patients who have retinal condition (retinal tear, exudate, hemorrhage) or history of retinal vein occlusion or central serous retinopathy or retinal pigment epithelial detachment; History of interstitial lung disease or pneumonitis; Patients who have clinically significant pleural effusion or ascites; Patients who have neurological condition (e.g., tremor, ataxia, hypotension, confusion), history of seizures or active central nervous system metastases; Impairment of gastrointestinal function or gastrointestinal disease (e.g., diarrhea, active ulcer disease, history of gastrointestinal perforation/hemorrhage, malabsorption or other conditions that under the judgment of the principal investigator (PI) may impair absorption of study drugs); Patients who are taking antineoplastic drugs for concomitant cancer or history of malignancy other than CCA within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%) such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer; Any other condition that would, in the Investigator s judgment, contraindicate the patients' participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection, unable to swallow medication, social/psychological issues, etc); Female patients who are pregnant or lactating at the time of enrollment.

ClinicalTrials.gov NCT05874414