Description:
The purpose of this first in human (FIH) trial is 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.
Title
- Brief Title: Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors
- Official Title: An Open-label, Multi-center, Phase I, Dose Finding Study of Oral TNO155 in Adult Patients With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
CTNO155X2101
- SECONDARY ID:
2016-001861-10
- NCT ID:
NCT03114319
Conditions
- Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12-mutant NSCLC,Esophageal SquamousCellCancer (SCC),Head/Neck SCC,Melanoma
Interventions
Drug | Synonyms | Arms |
---|
TNO155 | | TNO155 |
TNO155 in combination with EGF816 (nazartinib) | | TNO155 in combination with EGF816 (nazartinib) |
Purpose
The purpose of this first in human (FIH) trial is 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), will be
taken until the patient experiences unacceptable toxicity, progressive disease and/or
treatment is discontinued at the discretion of the investigator or the patient or due to
withdrawal of consent. Some patients will be participating in a food effect investigation as
an exploratory objective.
Trial Arms
Name | Type | Description | Interventions |
---|
TNO155 | Experimental | TNO155 for oral administration | |
TNO155 in combination with EGF816 (nazartinib) | Experimental | TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC | - TNO155 in combination with EGF816 (nazartinib)
|
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with adverse events |
Time Frame: | up to 5 years; at least once per treatment cycle |
Safety Issue: | |
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 |
Secondary Outcome Measures
Measure: | Overall response rate |
Time Frame: | From start of treatment for 60 months |
Safety Issue: | |
Description: | To evaluate the preliminary anti-tumor activity of TNO155 or of TNO155 in combination with EGF816 (nazartinib), e.g., overall response rate per RECIST 1.1 |
Measure: | pERK |
Time Frame: | At screening and between Cycle 1 and Cycle 3 on treatment for 60 months |
Safety Issue: | |
Description: | 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: | Area under the curve |
Time Frame: | 60 months |
Safety Issue: | |
Description: | Area under the plasma concentration time curve of TNO155 |
Measure: | Cmax |
Time Frame: | 60 months |
Safety Issue: | |
Description: | highest observed plasma concentration of TNO155 |
Measure: | tmax |
Time Frame: | 60 months |
Safety Issue: | |
Description: | Time of highest observed plasma concentration of TNO155 |
Measure: | apparent terminal elimination half-life |
Time Frame: | 60 months |
Safety Issue: | |
Description: | terminal elimination half-life of TNO155 |
Measure: | Area under the curve |
Time Frame: | 60 months |
Safety Issue: | |
Description: | Area under the plasma concentration time curve of TNO155 and EGF816 (nazartinib) when given in combination |
Measure: | Cmax |
Time Frame: | 60 months |
Safety Issue: | |
Description: | highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination |
Measure: | tmax |
Time Frame: | 60 months |
Safety Issue: | |
Description: | Time of highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination |
Measure: | apparent terminal elimination half-life |
Time Frame: | 60 months |
Safety Issue: | |
Description: | terminal elimination half-life of TNO155 and EGF816 (nazartinib) when given in combination |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial 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
Last Updated
July 27, 2021