Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12-mutant NSCLC,Esophageal SquamousCellCancer (SCC),Head/Neck SCC,Melanoma Clinical Trial
Official title:
An Open-label, Multi-center, Phase I, Dose Finding Study of Oral TNO155 in Adult Patients With Advanced Solid Tumors
| Verified date | June 2024 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 227 |
| Est. completion date | June 11, 2025 |
| Est. primary completion date | June 11, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 99 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Canada | Novartis Investigative Site | Toronto | Ontario |
| Italy | Novartis Investigative Site | Milano | MI |
| Japan | Novartis Investigative Site | Kobe-shi | Hyogo |
| Korea, Republic of | Novartis Investigative Site | Seoul | |
| Korea, Republic of | Novartis Investigative Site | Seoul | |
| Netherlands | Novartis Investigative Site | Amsterdam | |
| Netherlands | Novartis Investigative Site | Rotterdam | |
| Singapore | Novartis Investigative Site | Singapore | |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| Spain | Novartis Investigative Site | Hospitalet de LLobregat | Catalunya |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Taiwan | Novartis Investigative Site | Taipei | |
| United States | Dana Farber Cancer Center | Boston | Massachusetts |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Memorial Sloane Ketterin Cancer Ctr Main Centre | New York | New York |
| United States | NYU Langone Health . | New York | New York |
| United States | H Lee Moffitt Cancer Center and Research Institute . | Tampa | Florida |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Canada, Italy, Japan, Korea, Republic of, Netherlands, Singapore, Spain, Taiwan,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of participants with 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, cardiac imaging and ophthalmological assessments | up to 5 years; at least once per treatment cycle | |
| Primary | 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) | up to 28-day cycle | |
| Secondary | Overall response rate | 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 | From start of treatment for 60 months | |
| Secondary | pERK | 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 | At screening and between Cycle 1 and Cycle 3 on treatment for 60 months | |
| Secondary | Area under the curve | Area under the plasma concentration time curve of TNO155 | 60 months | |
| Secondary | Cmax | highest observed plasma concentration of TNO155 | 60 months | |
| Secondary | tmax | Time of highest observed plasma concentration of TNO155 | 60 months | |
| Secondary | apparent terminal elimination half-life | terminal elimination half-life of TNO155 | 60 months | |
| Secondary | Area under the curve | Area under the plasma concentration time curve of TNO155 and EGF816 (nazartinib) when given in combination | 60 months | |
| Secondary | Cmax | highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination | 60 months | |
| Secondary | tmax | Time of highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination | 60 months | |
| Secondary | apparent terminal elimination half-life | terminal elimination half-life of TNO155 and EGF816 (nazartinib) when given in combination | 60 months |