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

Primary Purpose

Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12-mutant NSCLC,Esophageal SquamousCellCancer (SCC),Head/Neck SCC,Melanoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TNO155
TNO155 in combination with EGF816 (nazartinib)
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12-mutant NSCLC,Esophageal SquamousCellCancer (SCC),Head/Neck SCC,Melanoma focused on measuring 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

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • H Lee Moffitt Cancer Center and Research Institute .Recruiting
  • Dana Farber Cancer Center
  • NYU Langone Health .Recruiting
  • Memorial Sloane Kettering Cancer Center Main CentreRecruiting
  • Sarah Cannon Research Institute
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

TNO155

TNO155 in combination with EGF816 (nazartinib)

Arm Description

TNO155 for oral administration

TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC

Outcomes

Primary Outcome Measures

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
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)

Secondary Outcome Measures

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
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
Area under the curve
Area under the plasma concentration time curve of TNO155
Cmax
highest observed plasma concentration of TNO155
tmax
Time of highest observed plasma concentration of TNO155
apparent terminal elimination half-life
terminal elimination half-life of TNO155
Area under the curve
Area under the plasma concentration time curve of TNO155 and EGF816 (nazartinib) when given in combination
Cmax
highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination
tmax
Time of highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination
apparent terminal elimination half-life
terminal elimination half-life of TNO155 and EGF816 (nazartinib) when given in combination

Full Information

First Posted
April 11, 2017
Last Updated
October 19, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03114319
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 26, 2017 (Actual)
Primary Completion Date
August 6, 2024 (Anticipated)
Study Completion Date
August 6, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12-mutant NSCLC,Esophageal SquamousCellCancer (SCC),Head/Neck SCC,Melanoma
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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
TNO155
Arm Type
Experimental
Arm Description
TNO155 for oral administration
Arm Title
TNO155 in combination with EGF816 (nazartinib)
Arm Type
Experimental
Arm Description
TNO155 in combination with EGF816 (nazartinib) in patients with advanced EGFR mutant NSCLC
Intervention Type
Drug
Intervention Name(s)
TNO155
Intervention Description
TNO155 for oral administration
Intervention Type
Drug
Intervention Name(s)
TNO155 in combination with EGF816 (nazartinib)
Intervention Description
TNO155 for oral administration; EGF816 (nazartinib) for oral administration
Primary Outcome Measure Information:
Title
Number of participants with adverse events
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
Time Frame
up to 5 years; at least once per treatment cycle
Title
Number of participants with dose limiting toxicities
Description
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)
Time Frame
up to 28-day cycle
Secondary Outcome Measure Information:
Title
Overall response rate
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
Time Frame
From start of treatment for 60 months
Title
pERK
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
Time Frame
At screening and between Cycle 1 and Cycle 3 on treatment for 60 months
Title
Area under the curve
Description
Area under the plasma concentration time curve of TNO155
Time Frame
60 months
Title
Cmax
Description
highest observed plasma concentration of TNO155
Time Frame
60 months
Title
tmax
Description
Time of highest observed plasma concentration of TNO155
Time Frame
60 months
Title
apparent terminal elimination half-life
Description
terminal elimination half-life of TNO155
Time Frame
60 months
Title
Area under the curve
Description
Area under the plasma concentration time curve of TNO155 and EGF816 (nazartinib) when given in combination
Time Frame
60 months
Title
Cmax
Description
highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination
Time Frame
60 months
Title
tmax
Description
Time of highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination
Time Frame
60 months
Title
apparent terminal elimination half-life
Description
terminal elimination half-life of TNO155 and EGF816 (nazartinib) when given in combination
Time Frame
60 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
trialandresults.registries@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
H Lee Moffitt Cancer Center and Research Institute .
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lina Gant
Phone
888-663-3488
Email
Lina.Gant@moffitt.org
First Name & Middle Initial & Last Name & Degree
Ahmad Tarhini
Facility Name
Dana Farber Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Completed
Facility Name
NYU Langone Health .
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kimberly Frias
Email
Kimberly.frias@nyulangone.org
First Name & Middle Initial & Last Name & Degree
Janice Mehnert
Facility Name
Memorial Sloane Kettering Cancer Center Main Centre
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Puja Chadha
Phone
656-888-4563
Email
chadhap@mskcc.org
First Name & Middle Initial & Last Name & Degree
Helena Yu
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37221
Country
United States
Individual Site Status
Completed
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1Z5
Country
Canada
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20141
Country
Italy
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kobe-shi
State/Province
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Leiden
ZIP/Postal Code
2300 RC
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Rotterdam
ZIP/Postal Code
3075 EA
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
168583
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hospitalet de LLobregat
State/Province
Catalunya
ZIP/Postal Code
08907
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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