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

NCT ID: NCT03114319

Last Updated: 2025-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 227 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-26
• Study Completion Date: 2025-07-04

Brief Summary

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.

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TNO155

TNO155 for oral administration

Group Type: EXPERIMENTAL

TNO155

Intervention Type: DRUG

TNO155 for oral administration

TNO155 in combination with EGF816 (nazartinib)

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

Group Type: EXPERIMENTAL

TNO155 in combination with EGF816 (nazartinib)

Intervention Type: DRUG

TNO155 for oral administration; EGF816 (nazartinib) for oral administration

Interventions

TNO155

TNO155 for oral administration

Intervention Type: DRUG

TNO155 in combination with EGF816 (nazartinib)

TNO155 for oral administration; EGF816 (nazartinib) for oral administration

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Dana Farber Cancer Center

Boston, Massachusetts, United States

Memorial Sloane Ketterin Cancer Ctr

New York, New York, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Novartis Investigative Site

Toronto, Ontario, Canada

Novartis Investigative Site

Milan, MI, Italy

Novartis Investigative Site

Kobe, , Japan

Novartis Investigative Site

Rotterdam, South Holland, Netherlands

Novartis Investigative Site

Amsterdam, , Netherlands

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Taipei, , Taiwan

Countries

United States; Canada; Italy; Japan; Netherlands; Singapore; South Korea; Spain; Taiwan

Other Identifiers

2023-508925-29-00

Identifier Type: OTHER

Identifier Source: secondary_id

CTNO155X2101

Identifier Type: -

Identifier Source: org_study_id