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

NCT03114319 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CTNO155X21012023-508925-29-00
• Study Type: interventional
• Target: 227
• Locations: 9 countries
• Sites: 18

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.

Conditions

KRAS G12-mutant NSCLC; Esophageal Squamous Cell Cancer (SCC); Head/Neck SCC; Melanoma; Advanced Gastrointestinal Stromal Tumors (GIST); Advanced NRAS/BRAFT wt Cutaneous Melanoma; Advanced EGFR Mutant Non Small Cell LungCancer (NSCLC)

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

Outcome Measures

Primary Outcomes (4)

• Number of participants with adverse events and serious 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 and cardiac biomarkers

  up to 5 years; at least once per treatment cycle

• 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)

  up to 28-day cycle

• Number of participants with dose interruptions and reductions

  Assessment of tolerability. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments may be permitted in order to allow patients to continue the study treatment

  Up to 5 years

• Dose intensity of study drugs

  Dose intensity is computed as the ratio of actual cumulative dose received to actual duration of exposure

  Up to 5 years

Secondary Outcomes (9)

• Overall response rate (ORR) per RECIST v1.1

  From start of treatment for 60 months

• Disease control rate (DCR) per RECIST v1.1

  From start of treatment for 60 months

• Progression-free survival (PFS) per RECIST v1.1

  Up to 5 years

• Duration of response (DOR) per RECIST v1.1

  Up to 5 years

• Change from baseline in DUSP6 in tumor samples

  At screening and between Cycle 1 and Cycle 3. One cycle=either 21 days or 28 days, depending on the cohort's treatment schedule.

Study Arms (2)

TNO155

EXPERIMENTAL

TNO155 for oral administration

Drug: TNO155

TNO155 in combination with EGF816 (nazartinib)

EXPERIMENTAL

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

Drug: TNO155 in combination with EGF816 (nazartinib)

Interventions

TNO155 DRUG

TNO155 for oral administration

TNO155

TNO155 in combination with EGF816 (nazartinib) DRUG

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

TNO155 in combination with EGF816 (nazartinib)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Dana Farber Cancer Center

Boston, Massachusetts, 02215, United States

Location

Memorial Sloane Ketterin Cancer Ctr

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37221, United States

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Milan, MI, 20141, Italy

Location

Novartis Investigative Site

Kobe, 650-0017, Japan

Location

Novartis Investigative Site

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Novartis Investigative Site

Amsterdam, 1066 CX, Netherlands

Location

Novartis Investigative Site

Singapore, 168583, Singapore

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Links

• CTNO155X2101 Clinical Trial Results Summary

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Melanoma; Squamous Cell Carcinoma of Head and Neck; Noonan Syndrome

Interventions

nazartinib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 14, 2017
• Study Start: May 26, 2017
• Primary Completion: July 4, 2025
• Study Completion: July 4, 2025
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); IT (1); ES (5); JP (1); KR (2); CA (1); SG (1); TW (1); NL (2)