A Phase 1 interventional study of TNO155 and TNO155 in combination with EGF816 (nazartinib) in Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC), KRAS G12-mutant NSCLC and Esophageal Squamous Cell Cancer (SCC), sponsored by Novartis Pharmaceuticals. Terminated at 18 sites in 9 countries. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-07-09.
Sponsored by Novartis Pharmaceuticals · Phase 1, Interventional, and Treatment
The purpose of this first in human (FIH) trial was to characterize the safety and tolerability of the SHP2 inhibitor TNO155 alone and in combination with EGF816 (nazartinib) and identify a recommended dose for future studies in adult patients with advanced solid tumors in selected indications.
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. The study treatment, TNO155 alone or in combination with EGF816 (nazartinib), was taken until the patient experienced unacceptable toxicity, progressive disease and/or treatment was discontinued at the discretion of the investigator or the patient or due to withdrawal of consent.
646 studies on the registry are indexed under Esophageal Squamous Cell Carcinoma; 275 are open to participants now.
This study's enrollment of 227 is above the median of 65 across 540 interventional studies indexed under Esophageal Squamous Cell Carcinoma.
Browse Esophageal Squamous Cell Carcinoma studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
ECOG (Eastern cooperative oncology group) performance status ≤2
Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):
Exclusion Criteria:
Insufficient hepatic and renal function.
Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):
TNO155 for oral administration
Drug: TNO155
TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC
Drug: TNO155 in combination with EGF816 (nazartinib)
TNO155 for oral administration
TNO155 for oral administration; EGF816 (nazartinib) for oral administration
Number of participants with adverse events and serious adverse events
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 and cardiac biomarkers
Time frame: up to 5 years; at least once per treatment cycle
Number of participants with dose limiting toxicities
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 or with TNO155 in combination with EGF816 (nazartinib)
Time frame: up to 28-day cycle
Number of participants with dose interruptions and reductions
Assessment of tolerability. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments may be permitted in order to allow patients to continue the study treatment
Time frame: Up to 5 years
Dose intensity of study drugs
Dose intensity is computed as the ratio of actual cumulative dose received to actual duration of exposure
Time frame: Up to 5 years
Overall response rate (ORR) per RECIST v1.1
ORR is the proportion of patients with a best overall response of Complete Response (CR) or Partial response (PR)
Time frame: From start of treatment for 60 months
Disease control rate (DCR) per RECIST v1.1
DCR is the proportion of patients with a best overall response of CR or PR or stable disease (SD)
Time frame: From start of treatment for 60 months
Progression-free survival (PFS) per RECIST v1.1
PFS is the time from date start of treatment to the date of event defined as the first documented progression or death due to any cause
Time frame: Up to 5 years
Duration of response (DOR) per RECIST v1.1
DOR is the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause
Time frame: Up to 5 years
Change from baseline in DUSP6 in tumor samples
Dual Specificity Phosphatase 6 (DUSP6) mRNA levels assessed in paired tumor biopsy samples by quantitative polymerase chain reaction (qPCR)
Time frame: At screening and between Cycle 1 and Cycle 3. One cycle=either 21 days or 28 days, depending on the cohort's treatment schedule.
Area under the plasma concentration-time curve (AUC) of study drugs
Pharmacokinetic (PK) parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods
Time frame: From pre-dose up to 48 hours post-dose on Cycle 1 Day 1 and from pre-dose up to 24 hours post-dose on Cycle 1 Day 14. One cycle=21 days or 28 days, depending on the dosing schedule.
Peak plasma concentration (Cmax) of study drugs
PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods
Time frame: From pre-dose up to 48 hours post-dose on Cycle 1 Day 1 and from pre-dose up to 24 hours post-dose on Cycle 1 Day 14. One cycle=21 days or 28 days, depending on the dosing schedule.
Time to reach peak plasma concentration (Tmax) of study drugs
PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods
Time frame: From pre-dose up to 48 hours post-dose on Cycle 1 Day 1 and from pre-dose up to 24 hours post-dose on Cycle 1 Day 14. One cycle=21 days or 28 days, depending on the dosing schedule.
Apparent terminal elimination half-life of study drugs
PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods
Time frame: From pre-dose up to 48 hours post-dose on Cycle 1 Day 1 and from pre-dose up to 24 hours post-dose on Cycle 1 Day 14. One cycle=21 days or 28 days, depending on the dosing schedule.
Plan to share: No
This study is terminated, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Esophageal Squamous Cell Carcinoma→
Novartis Pharmaceuticals