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

Novartis

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Drug: TNO155; Drug: TNO155 in combination with EGF816 (nazartinib)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03114319

CTNO155X2101

2016-001861-10 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 227 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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227 participants in 2 patient groups

TNO155

Experimental group

Description:

TNO155 for oral administration

Treatment:

Drug: TNO155

TNO155 in combination with EGF816 (nazartinib)

Experimental group

Description:

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

Treatment:

Drug: TNO155 in combination with EGF816 (nazartinib)