Clinical Trials /

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

NCT03114319

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
TNO155TNO155
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

NameTypeDescriptionInterventions
TNO155ExperimentalTNO155 for oral administration
  • TNO155
TNO155 in combination with EGF816 (nazartinib)ExperimentalTNO155 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

May 11, 2020