Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC)Phase 1NCT03114319
Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors
A Phase 1 study testing TNO155 and TNO155 in combination with EGF816 (nazartinib) in people with Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC) and KRAS G12-mutant NSCLC, run by Novartis Pharmaceuticals at 18 sites in 9 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC), KRAS G12-mutant NSCLC, Esophageal Squamous Cell Cancer (SCC)
- What is being tested?
- TNO155 and TNO155 in combination with EGF816 (nazartinib)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 227 participants
- Where
- 18 sitesin 9 countries
- Study dates
- 26 May 2017to 4 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to understand and voluntarily sign the ICF and able to comply with the study visit schedule and the other protocol requirements.
- Patient (male or female) ≥18 years of age willing to agree to not father a child/become pregnant and comply with effective contraception criteria.
- 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.
- ECOG (Eastern cooperative oncology group) performance status ≤2
- Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):
- Patients must be screened for Hepatitis B virus and Hepatitis C virus
Who cannot join
- Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations. (Exceptions are KRAS G12-mutant NSCLC's)
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- 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.
- Clinically significant cardiac disease.
- Active diarrhea or inflammatory bowel disease
- Insufficient bone marrow function
Show all 14Show fewer
- Insufficient hepatic and renal function.
- Additional criteria only appying to TNO155 in combination with EGF816 (nazartinib):
- Patients with a known history of human immunodeficiency virus (HIV) seropositivity.
- Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use at the time of study entry.
- Patients who have undergone a bone marrow or solid organ transplant
- Patients with a history or presence of interstitial lung disease or interstitial pneumonitis
- Bullous and exfoliative skin disorders at screening of any grade
- Presence of clinically significant ophthalmological abnormalities that might increase the risk of corneal epithelial injury
Trial locations and contacts
18 sites in 9 countries.
18 sites in 9 countries
Spain5 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
L'Hospitalet de Llobregat, Barcelona, 08907
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28040
United States4 sites
Dana Farber Cancer Center
Boston, Massachusetts, 02215
Sarah Cannon Research Institute
Nashville, Tennessee, 37221
Memorial Sloane Ketterin Cancer Ctr
New York, New York, 10065
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Netherlands2 sites
Novartis Investigative Site
Amsterdam, 1066 CX
Novartis Investigative Site
Rotterdam, South Holland, 3015 GD
South Korea2 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 05505
About this study
Official title: 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.
Read the 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.
- Conditions
- Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC), KRAS G12-mutant NSCLC, Esophageal Squamous Cell Cancer (SCC), Head/Neck SCC, Melanoma, Advanced Gastrointestinal Stromal Tumors (GIST)
- Being tested
- TNO155, TNO155 in combination with EGF816 (nazartinib)
- Keywords
- TNO155, SHP2, advanced solid tumor, NSCLC, HNSCC, Esophageal SCC, Melanoma, EGFR, KRAS G12C, GIST, PTPN11, cancers with a mass, bulky tumor, nodule, lump, advanced solid malignancies
- Medical subject headings
- Esophageal Squamous Cell Carcinoma, Melanoma, Squamous Cell Carcinoma of Head and Neck, Noonan Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNO155Drug
TNO155 for oral administration
TNO155 in combination with EGF816 (nazartinib)Drug
TNO155 for oral administration; EGF816 (nazartinib) for oral administration
| Study group | Role | What they receive |
|---|---|---|
| TNO155 | Experimental | TNO155 for oral administration Receives: Drug: TNO155 |
| TNO155 in combination with EGF816 (nazartinib) | Experimental | TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC Receives: Drug: TNO155 in combination with EGF816 (nazartinib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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
Measured: 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
Measured: Up to 5 years
Secondary outcomes (9)
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)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2017
- Study start26 May 2017
- Primary completion4 Jul 2025
- Study completion4 Jul 2025
Why it stopped: Business reasons and not due to any safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 227 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03114319
- Sponsor's protocol ID
- CTNO155X2101
- Other IDs
- 2023-508925-29-00, 2023
- Status last verified
- Jul 2026
- First submitted
- 11 Apr 2017
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center, Phase I, Dose Finding Study of Oral TNO155 in Adult Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03114319
- Acronym / sponsor ID
- CTNO155X2101
- Conditions
- Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC), KRAS G12-mutant NSCLC, Esophageal Squamous Cell Cancer (SCC), Head/Neck SCC, Melanoma, Advanced Gastrointestinal Stromal Tumors (GIST)
- Keywords
- TNO155, SHP2, advanced solid tumor, NSCLC, HNSCC, Esophageal SCC, Melanoma, EGFR
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons and not due to any safety concerns
- Enrolment
- 227 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 May 2017 (actual)
- Primary completion
- 4 Jul 2025 (actual)
- Study completion
- 4 Jul 2025 (actual)
- First posted
- 14 Apr 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TNO155 | Experimental | Drug: TNO155TNO155 for oral administration |
| TNO155 in combination with EGF816 (nazartinib) | Experimental | Drug: TNO155 in combination with EGF816 (nazartinib)TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Able to understand and voluntarily sign the ICF and able to comply with the study visit schedule and the other protocol requirements.
- Patient (male or female) ≥18 years of age willing to agree to not father a child/become pregnant and comply with effective contraception criteria.
- 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.
- ECOG (Eastern cooperative oncology group) performance status ≤2
- Patients must be screened for Hepatitis B virus and Hepatitis C virus
Key exclusion criteria (14 listed)
- Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations. (Exceptions are KRAS G12-mutant NSCLC's)
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- 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.
- Clinically significant cardiac disease.
- Active diarrhea or inflammatory bowel disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNO155TNO155 for oral administration | Drug | TNO155 |
| TNO155 in combination with EGF816 (nazartinib)TNO155 for oral administration; EGF816 (nazartinib) for oral administration | Drug | TNO155 in combination with EGF816 (nazartinib) |
Primary outcome
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
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)
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
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
9 secondary outcomes
Overall response rate (ORR) per RECIST v1.1
Time frame: From start of treatment for 60 months
Disease control rate (DCR) per RECIST v1.1
Time frame: From start of treatment for 60 months
Progression-free survival (PFS) per RECIST v1.1
Time frame: Up to 5 years
Duration of response (DOR) per RECIST v1.1
Time frame: 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.
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.
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.
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.
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.
Results and safety
The study was stopped early (reason given: Business reasons and not due to any safety concerns). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- CTNO155X2101 Clinical Trial Results SummaryLink provided by the sponsor.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
18 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TNO155 and TNO155 in combination with EGF816 (nazartinib) in people with Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC) and KRAS G12-mutant NSCLC, run by Novartis Pharmaceuticals at 18 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Spain, United States, Netherlands, South Korea, Canada and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business reasons and not due to any safety concerns). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events and serious adverse events (time frame: up to 5 years; at least once per treatment cycle). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.