Study of INC280 in Patients With c-MET Dependent Advanced Solid Tumors

A Phase I Open-label Dose Escalation Study With Expansion to Assess the Safety and Tolerability of INC280 in Patients With c-MET Dependent Advanced Solid Tumors

This study will assess the safety and efficacy of INC280 in patients with solid tumors that are refractory to current treatment or for which there is not a current standard of care and whose tumors have dysregulation of the c-MET pathway.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: INC280

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Novartis Investigative Site
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Novartis Investigative Site
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• France
  • LILLE Cédex, France, 59037
    • Novartis Investigative Site
  • La Tronche, France, 38700
    • Novartis Investigative Site
  • Strasbourg Cedex, France, 67091
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Oldenburg, Germany, 26121
    • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
  • Shatin, New Territories, Hong Kong
    • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3525408
    • Novartis Investigative Site
  • Kfar Saba, Israel, 4428164
    • Novartis Investigative Site
  • Ramat Gan, Israel, 5265601
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Novartis Investigative Site
• Italy
  • AN
    • Ancona, AN, Italy, 60126
      • Novartis Investigative Site
  • FC
    • Meldola, FC, Italy, 47014
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20162
      • Novartis Investigative Site
    • Milano, MI, Italy, 20133
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
• Korea, Republic of
  • Gyeonggi Do
    • Seoul, Gyeonggi Do, Korea, Republic of, 03080
      • Novartis Investigative Site
  • Korea
    • Gyeonggi do, Korea, Korea, Republic of, 10408
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 05505
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 06351
      • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Novartis Investigative Site
  • Rotterdam, Netherlands, 3075 EA
    • Novartis Investigative Site
  • The Netherlands
    • Utrecht, The Netherlands, Netherlands, 3508 GA
      • Novartis Investigative Site
• Norway
  • Oslo, Norway, NO-0424
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169610
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Andalucia
    • Granada, Andalucia, Spain, 18014
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
• Taiwan
  • Taiwan ROC
    • Tainan, Taiwan ROC, Taiwan, 70403
      • Novartis Investigative Site
    • Taipei, Taiwan ROC, Taiwan, 10041
      • Novartis Investigative Site
• Thailand
  • Hat Yai
    • Songkhla, Hat Yai, Thailand, 90110
      • Novartis Investigative Site
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago SC
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute Wayne St Karmanos
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute Dept of Onc
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas/MD Anderson Cancer Center Dept of Onc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must have evidence of c-MET dysregulation from either local data or the results of molecular pre-screening evaluations.
• Confirmed diagnosis of a solid tumor.
• Measureable lesion.
• Refractory to currently available treatment or no therapies available.
• 18 years or older.
• ECOG performance status of 0, 1, or 2.
• Obtained written informed consent.

Additional inclusion criteria for NSCLC patients EGFRwt with high c-MET expression:

• Written documentation of EGFRwt NSCLC.
• Written documentation of c-MET positivity.
• Patients should not have received more than three prior lines of antineoplastic therapy for NSCLC.
• Presence of at least one measurable lesion as determined by modified RECIST version 1.1

Exclusion Criteria:

HCC with liver dysfunction greater than Child-Pugh A. Previous treatment with a c-MET inhibitor or HGF-targeting therapy. Symptomatic CNS metastases that are neurologically unstable or requiring increasing doses of steroids to control their CNS disease.

Any CNS deficits. For patients with GBM, CNS symptoms grade 2 or greater. Subjects with significant or uncontrolled cardiovascular disease (eg, uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months of starting study treatment or heart attack within 12 months of starting study treatment.

Receiving anti-epileptic drugs that are known to be strong inducers of CYP3A4. Prior or current anti-angiogenic therapy for patients with GBM. Radiation therapy within ≤ 4 weeks (< 12 for GBM) prior to the first dose of study drug or limited field radiotherapy within ≤ 2 weeks (< 12 weeks GBM) prior to the start of study treatment. Any persistent side effect of prior radiotherapy must be resolved to ≤ Grade 1 prior to the first dose of study drug.

Additional exclusion criteria for NSCLC patients EGFRwt with high c-MET expression:

• Patients who have received more than three prior lines of antineoplastic therapies
• Any unresolved toxicity (CTCAE grade > 1) from previous anti-cancer therapy or radiotherapy, except alopecia

• Patients have received anti-cancer therapies within the following time frames prior to the first dose of study treatment:

  • Conventional cytotoxic chemotherapy: ≤4 weeks (≤6 weeks for nitrosoureas and mitomycin-C)
  • Biologic therapy (e.g., antibodies): ≤4 weeks
  • Non-cytotoxic small molecule therapeutics: ≤5 half-lives or ≤2 weeks (whichever is longer)
  • Other investigational agents: ≤4 weeks
  • Radiation therapy (palliative setting is allowed.): ≤4 weeks
  • Major surgery: ≤2 weeks

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INC280	Drug: INC280

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence rate of dose-limiting toxicities and adverse events	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response by local investigator assessment	2 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Schuler M, Berardi R, Lim WT, de Jonge M, Bauer TM, Azaro A, Gottfried M, Han JY, Lee DH, Wollner M, Hong DS, Vogel A, Delmonte A, Akimov M, Ghebremariam S, Cui X, Nwana N, Giovannini M, Kim TM. Molecular correlates of response to capmatinib in advanced non-small-cell lung cancer: clinical and biomarker results from a phase I trial. Ann Oncol. 2020 Jun;31(6):789-797. doi: 10.1016/j.annonc.2020.03.293. Epub 2020 Mar 30.
• Bang YJ, Su WC, Schuler M, Nam DH, Lim WT, Bauer TM, Azaro A, Poon RTP, Hong D, Lin CC, Akimov M, Ghebremariam S, Zhao S, Giovannini M, Ma B. Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts. Cancer Sci. 2020 Feb;111(2):536-547. doi: 10.1111/cas.14254. Epub 2019 Dec 30.

Helpful Links

• Results for INC280X2102 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): February 29, 2012
• Primary Completion (Actual): July 4, 2017
• Study Completion (Actual): July 4, 2017

Study Registration Dates

• First Submitted: March 25, 2011
• First Submitted That Met QC Criteria: March 28, 2011
• First Posted (Estimate): March 29, 2011

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer,; hepatocellular,; gastric,; renal cell,; c-MET,; refractory,; glioblastoma,; breast,; nasopharyngeal,; confirmed evidence of c-MET dysregulation
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CINC280X2102; 2010-024101-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No