Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors

April 13, 2026 updated by: Novartis Pharmaceuticals

An Open-label, Multi-center, Phase I, Dose Finding Study of Oral TNO155 in Adult Patients With Advanced Solid Tumors

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

227

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
  • Italy
    • MI
      • Milan, MI, Italy, 20141
        • Novartis Investigative Site
  • Japan
      • Kobe, Japan, 650-0017
        • Novartis Investigative Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • Novartis Investigative Site
    • South Holland
      • Rotterdam, South Holland, Netherlands, 3015 GD
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 168583
        • Novartis Investigative Site
  • South Korea
      • Seoul, South Korea, 03080
        • Novartis Investigative Site
      • Seoul, South Korea, 05505
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28034
        • Novartis Investigative Site
      • Madrid, Spain, 28040
        • Novartis Investigative Site
      • Madrid, Spain, 28009
        • Novartis Investigative Site
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Novartis Investigative Site
    • Catalonia
      • Barcelona, Catalonia, Spain, 08035
        • Novartis Investigative Site
  • Taiwan
      • Taipei, Taiwan, 10002
        • Novartis Investigative Site
  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H Lee Moffitt Cancer Center and Research Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloane Ketterin Cancer Ctr
    • Tennessee
      • Nashville, Tennessee, United States, 37221
        • Sarah Cannon Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Able to understand and voluntarily sign the ICF and able to comply with the study visit schedule and the other protocol requirements.
  2. Patient (male or female) ≥18 years of age willing to agree to not father a child/become pregnant and comply with effective contraception criteria.
  3. Must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or is appropriate.

  4. ECOG (Eastern cooperative oncology group) performance status ≤2

    Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):

  5. Patients must be screened for Hepatitis B virus and Hepatitis C virus

Exclusion Criteria:

  1. Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations. (Exceptions are KRAS G12-mutant NSCLC's)
  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.
  4. Clinically significant cardiac disease.
  5. Active diarrhea or inflammatory bowel disease
  6. Insufficient bone marrow function

  7. Insufficient hepatic and renal function.

    Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):

  8. Patients with a known history of human immunodeficiency virus (HIV) seropositivity.
  9. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry.
  10. Patients who have undergone a bone marrow or solid organ transplant
  11. Patients with a history or presence of interstitial lung disease or interstitial pneumonitis
  12. Bullous and exfoliative skin disorders at screening of any grade
  13. Presence of clinically significant ophthalmological abnormalities that might increase the risk of corneal epithelial injury

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TNO155
TNO155 for oral administration
Drug: TNO155
TNO155 for oral administration
Experimental: TNO155 in combination with EGF816 (nazartinib)
TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC
Drug: TNO155 in combination with EGF816 (nazartinib)
TNO155 for oral administration; EGF816 (nazartinib) for oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with dose limiting toxicities
Time Frame: up to 28-day cycle
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)
up to 28-day cycle
Number of participants with adverse events and serious adverse events
Time Frame: up to 5 years; at least once per treatment cycle
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
up to 5 years; at least once per treatment cycle
Number of participants with dose interruptions and reductions
Time Frame: Up to 5 years
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
Up to 5 years
Dose intensity of study drugs
Time Frame: Up to 5 years
Dose intensity is computed as the ratio of actual cumulative dose received to actual duration of exposure
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR) per RECIST v1.1
Time Frame: From start of treatment for 60 months
ORR is the proportion of patients with a best overall response of Complete Response (CR) or Partial response (PR)
From start of treatment for 60 months
Disease control rate (DCR) per RECIST v1.1
Time Frame: From start of treatment for 60 months
DCR is the proportion of patients with a best overall response of CR or PR or stable disease (SD)
From start of treatment for 60 months
Progression-free survival (PFS) per RECIST v1.1
Time Frame: Up to 5 years
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
Up to 5 years
Duration of response (DOR) per RECIST v1.1
Time Frame: Up to 5 years
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
Up to 5 years
Change from baseline in DUSP6 in tumor samples
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.
Dual Specificity Phosphatase 6 (DUSP6) mRNA levels assessed in paired tumor biopsy samples by quantitative polymerase chain reaction (qPCR)
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
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.
Pharmacokinetic (PK) parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods
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
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.
PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods
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
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.
PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods
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
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.
PK parameters calculated based on the plasma concentrations versus time profiles by using non-compartmental methods
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 26, 2017

Primary Completion (Actual)

July 4, 2025

Study Completion (Actual)

July 4, 2025

Study Registration Dates

First Submitted

April 11, 2017

First Submitted That Met QC Criteria

April 11, 2017

First Posted (Actual)

April 14, 2017

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

April 13, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CTNO155X2101
  • 2023-508925-29-00 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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