Clinical Trial - NCT03114319

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

Recruiting

Sponsor: Novartis Pharmaceuticals

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03114319

Protocol Info

Short Description: Phase I of Oral TNO155 in Advanced Solid Tumors
Long Description: An Open-label, Multi-center, Phase I, Dose Finding Study of Oral TNO155 in Adult Patients With Advanced Solid Tumors
MGH Status: Open
Sponsor: Novartis
Disease Program: Phase I

Next Steps


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Purpose

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 Title Intervention Phase
Advanced EGFRmutant NonSmallSellLungCancer (NSCLC),KRAS G12-mutant NSCLC,Esophageal SquamousCellCanc TNO155 TNO155 in combination with EGF816 (nazartinib) Phase 1
Study Type Interventional
Official Title An Open-label, Multi-center, Phase I, Dose Finding Study of Oral TNO155 in Adult Patients With Advanced Solid Tumors

Primary Outcome Measures

Number of participants with adverse events [Time Frame: up to 5 years; at least once per treatment cycle] [Designated as safety issue: ]

Number of participants with dose limiting toxicities [Time Frame: up to 28-day cycle] [Designated as safety issue: ]


Secondary Outcome Measures

Overall response rate [Time Frame: From start of treatment for 60 months] [Designated as safety issue: ]

pERK [Time Frame: At screening and between Cycle 1 and Cycle 3 on treatment for 60 months] [Designated as safety issue: ]

Area under the curve [Time Frame: 60 months] [Designated as safety issue: ]

Cmax [Time Frame: 60 months] [Designated as safety issue: ]

tmax [Time Frame: 60 months] [Designated as safety issue: ]

apparent terminal elimination half-life [Time Frame: 60 months] [Designated as safety issue: ]

Area under the curve [Time Frame: 60 months] [Designated as safety issue: ]

Cmax [Time Frame: 60 months] [Designated as safety issue: ]

tmax [Time Frame: 60 months] [Designated as safety issue: ]

apparent terminal elimination half-life [Time Frame: 60 months] [Designated as safety issue: ]

Estimated Enrollment: 255
Study Start Date: May 2017
Estimated Study Completion Date: August 2022
Estimated Primary Completion Date: August 2022
Arms Assigned Interventions

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

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly 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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03114319

Locations

  • United States, Massachusetts
    • Dana Farber Cancer Center Boston, Massachusetts, United States, 02215
  • United States, New York
    • Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065
  • United States, Tennessee
    • Sarah Cannon Research Institute Nashville, Tennessee, United States, 37221
  • Canada, Ontario
    • Novartis Investigative Site Toronto, Ontario, Canada, M5G 1Z5
  • Japan, Hyogo
    • Novartis Investigative Site Kobe-shi, Hyogo, Japan, 650-0017
  • Netherlands,
    • Novartis Investigative Site Amsterdam, , Netherlands, 1066 CX
    • Novartis Investigative Site Rotterdam, , Netherlands, 3075 EA
  • Singapore,
    • Novartis Investigative Site Singapore, , Singapore, 169610
  • Spain, Catalunya
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08035
    • Novartis Investigative Site Hospitalet de LLobregat, Catalunya, Spain, 08907

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03114319
Other Study ID Numbers: 2016-001861-10
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Novartis:

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:

Melanoma

(R,E)-N-(7-chloro-1-(1-(4-(dimethylamino)but-2-enoyl)azepan-3-yl)-1H-benzo(d)imidazol-2-yl)-2-methylisonicotinamide

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on October 14, 2020