The purpose of this first in human (FIH) trial is to characterize the safety and tolerability of the SHP2 inhibitor TNO155 and identify a recommended dose for future studies in adult patients with advanced solid tumors in selected indications.
Name: TNO155
Description: TNO155 for oral administrationType: DrugTNO155
Description: All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments
Measure: Number of participants with adverse events Time: up to 3 years; at least once per treatment cycleDescription: Incidence and nature of dose limiting toxicities (DLTs) in the dose escalation part. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle (either 21 days or 28 days, depending on the cohort's treatment schedule) with TNO155
Measure: Number of participants with dose limiting toxicities Time: up to 28-day cycleDescription: Area under the plasma concentration time curve of TNO155
Measure: Area under the curve Time: 30 monthsDescription: To evaluate the preliminary anti-tumor activity of TNO155, e.g., overall response rate per RECIST 1.1
Measure: Overall response rate Time: From start of treatment for 34 monthsDescription: On treatment versus baseline comparison of pharmacodynamic markers e.g., pERK (Phosphorylated form of Extracellular signal-regulated kinase) on newly obtained tumor samples by IHC
Measure: pERK Time: At screening and between Cycle 1 and Cycle 3 on treatment for 30 monthsDescription: highest observed plasma concentration of TNO155
Measure: Cmax Time: 30 monthsDescription: Time of highest observed plasma concentration of TNO155
Measure: tmax Time: 30 monthsDescription: terminal elimination half-life of TNO155
Measure: apparent terminal elimination half-life Time: 30 monthsAllocation: Non-Randomized
Single Group Assignment
There is one SNP
(Exceptions are KRAS G12C CRC and KRAS G12C NSCLC) 2. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. 3. Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. --- G12C ---
(Exceptions are KRAS G12C CRC and KRAS G12C NSCLC) 2. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. 3. Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. --- G12C --- --- G12C ---
Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12C NSCLC,CRC,Esophageal SquamousCellCancer (SCC),Head/Neck SCC,RAS/RAF Wild-type Other Solid Tumor This study has been designed as a Phase I, open-label, dose finding study with a dose escalation part and a dose expansion part in adult patients with selected advanced solid tumors. --- G12C ---