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

Purpose

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.

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)
  • Advanced NRAS/BRAFT wt Cutaneous Melanoma

Eligibility

Eligible Ages
Between 18 Years and 99 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
TNO155 		TNO155 for oral administration
  • Drug: TNO155
    TNO155 for oral administration
  • Drug: TNO155 in combination with EGF816 (nazartinib)
    TNO155 for oral administration; EGF816 (nazartinib) 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

More Details

Status
Terminated
Sponsor
Novartis Pharmaceuticals

Study Contact

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.