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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. Identifier: NCT03114319
Recruitment Status : Recruiting
First Posted : April 14, 2017
Last Update Posted : February 7, 2020
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 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 G12C NSCLC,CRC,Esophageal SquamousCellCancer (SCC),Head/Neck SCC,RAS/RAF Wild-type Other Solid Tumor Drug: TNO155 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, 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
Estimated Enrollment : 135 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

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

Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: up to 3 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

Secondary Outcome Measures :
  1. Area under the curve [ Time Frame: 30 months ]
    Area under the plasma concentration time curve of TNO155

  2. Overall response rate [ Time Frame: From start of treatment for 34 months ]
    To evaluate the preliminary anti-tumor activity of TNO155, e.g., overall response rate per RECIST 1.1

  3. pERK [ Time Frame: At screening and between Cycle 1 and Cycle 3 on treatment for 30 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

  4. Cmax [ Time Frame: 30 months ]
    highest observed plasma concentration of TNO155

  5. tmax [ Time Frame: 30 months ]
    Time of highest observed plasma concentration of TNO155

  6. apparent terminal elimination half-life [ Time Frame: 30 months ]
    terminal elimination half-life of TNO155

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

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

Exclusion Criteria:

  1. Tumors harboring known activating KRAS, NRAS, HRAS, BRAF or PTPN11 (SHP2) mutations. (Exceptions are KRAS G12C CRC and KRAS G12C NSCLC)
  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.

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 identifier (NCT number): NCT03114319

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Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals +41613241111

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United States, Massachusetts
Novartis Investigative Site Recruiting
Boston, Massachusetts, United States, 02215
Contact: Andrew Wolanski    617-632-6623   
Principal Investigator: Geoffrey Shapiro         
United States, New York
Novartis Investigative Site Recruiting
New York, New York, United States, 10065
Contact: Murielle Georges    656-888-4563   
Principal Investigator: Helena Yu         
United States, Tennessee
Novartis Investigative Site Recruiting
Nashville, Tennessee, United States, 37221
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M5G 1Z5
Novartis Investigative Site Recruiting
Kobe-shi, Hyogo, Japan, 650-0017
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1066 CX
Novartis Investigative Site Recruiting
Rotterdam, Netherlands, 3075 EA
Novartis Investigative Site Recruiting
Singapore, Singapore, 169610
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site Recruiting
Hospitalet de LLobregat, Catalunya, Spain, 08907
Sponsors and Collaborators
Novartis Pharmaceuticals
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals Identifier: NCT03114319    
Other Study ID Numbers: CTNO155X2101
2016-001861-10 ( EudraCT Number )
First Posted: April 14, 2017    Key Record Dates
Last Update Posted: February 7, 2020
Last Verified: February 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 ):
advanced solid tumor
Colorectal cancer (CRC)
cancers with a mass
bulky tumor
advanced solid malignancies
Esophageal SCC
Additional relevant MeSH terms:
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