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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03114319
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : May 13, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12-mutant NSCLC,Esophageal SquamousCellCancer (SCC),Head/Neck SCC,Melanoma Drug: TNO155 Drug: TNO155 in combination with EGF816 (nazartinib) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 255 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center, Phase I, Dose Finding Study of Oral TNO155 in Adult Patients With Advanced Solid Tumors
Actual Study Start Date : May 26, 2017
Estimated Primary Completion Date : August 2, 2022
Estimated Study Completion Date : August 2, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TNO155
TNO155 for oral administration
Drug: TNO155
TNO155 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




Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: up to 5 years; at least once per treatment cycle ]
    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

  2. Number of participants with dose limiting toxicities [ Time Frame: up to 28-day cycle ]
    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 :
  1. Overall response rate [ Time Frame: From start of treatment for 60 months ]
    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

  2. pERK [ Time Frame: At screening and between Cycle 1 and Cycle 3 on treatment for 60 months ]
    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

  3. Area under the curve [ Time Frame: 60 months ]
    Area under the plasma concentration time curve of TNO155

  4. Cmax [ Time Frame: 60 months ]
    highest observed plasma concentration of TNO155

  5. tmax [ Time Frame: 60 months ]
    Time of highest observed plasma concentration of TNO155

  6. apparent terminal elimination half-life [ Time Frame: 60 months ]
    terminal elimination half-life of TNO155

  7. Area under the curve [ Time Frame: 60 months ]
    Area under the plasma concentration time curve of TNO155 and EGF816 (nazartinib) when given in combination

  8. Cmax [ Time Frame: 60 months ]
    highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination

  9. tmax [ Time Frame: 60 months ]
    Time of highest observed plasma concentration of TNO155 and EGF816 (nazartinib) when given in combination

  10. apparent terminal elimination half-life [ Time Frame: 60 months ]
    terminal elimination half-life of TNO155 and EGF816 (nazartinib) when given in combination



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03114319


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 trialandresults.registries@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Massachusetts
Dana Farber Cancer Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Rachel Annese    617-643-1820    rannese2@mgh.harvard.edu   
Principal Investigator: Geoffrey Shapiro         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Murielle Georges    656-888-4563    georgesm@mskcc.org   
Principal Investigator: Helena Yu         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37221
Contact: Andrea Smith    615-329-7274    andrea.smith10@sarahcannon.com   
Principal Investigator: Melissa Johnson         
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 1Z5
Japan
Novartis Investigative Site Recruiting
Kobe-shi, Hyogo, Japan, 650-0017
Netherlands
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site Recruiting
Rotterdam, Netherlands, 3075 EA
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Hospitalet de LLobregat, Catalunya, Spain, 08907
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03114319    
Other Study ID Numbers: CTNO155X2101
2016-001861-10 ( EudraCT Number )
First Posted: April 14, 2017    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
(R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo(d)imidazol-2-yl)-2-methylisonicotinamide
Antineoplastic Agents