A Dose Escalation Study to Assess PK, Safety and Tolerability of INC280 When Taken With Food in cMET Dysregulated Advanced Solid Tumors.

A Multicenter, Open Label, Phase 1 Dose Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of INC280 Tablet Formulation With Food in Patients With cMET Dysregulated Advanced Solid Tumors.

Dose escalation study to assess PK, safety and tolerability of INC280 when taken with food in patients with cMET dysregulated advanced solid tumors.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Novartis Investigative Site
• Denmark
  • Herlev, Denmark, 2730
    • Novartis Investigative Site
• Germany
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
  • Galicia
    • Santiago de Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
• Sweden
  • Goteborg, Sweden, 413 45
    • Novartis Investigative Site
  • Lund, Sweden, SE-221 85
    • Novartis Investigative Site
  • Stockholm, Sweden, 171 76
    • Novartis Investigative Site
  • Uppsala, Sweden, SE-751 85
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Novartis Investigative Site
  • Manchester, United Kingdom, M20 4BX
    • Novartis Investigative Site
• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center SC

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:

• cMET dysregulated advanced solid tumor
• At least one measurable lesion as defined by RECIST 1.1
• Recovered from all toxicities related to prior anti-cancer therapies to grade ≤ 1
• Adequate organ function
• ECOG performance status (PS) ≤ 1

Exclusion Criteria:

• Prior treatment with crizotinib or any other cMET or HGF inhibitor
• Known hypersensitivity to any of the excipients of INC280
• Symptomatic central nervous system (CNS) metastases who are neurologically unstable
• Presence or history of a malignant disease other than the study related cancer
• Clinically significant, uncontrolled heart diseases
• Thoracic radiotherapy to lung fields ≤ 4 weeks prior to starting INC280 or patients who have not recovered from radiotherapy-related toxicities
• Major surgery within 4 weeks prior to starting INC280
• Impairment of GI function
• Patients receiving unstable or increasing doses of corticosteroids
• Patients receiving treatment with any enzyme-inducing anticonvulsant
• Pregnant or nursing (lactating) women Other protocol-related 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 of Dose limiting toxiticites (DLTs)	During the first 28 days on INC280 treatment; cycle = 21 days
Frequency of DLTs	During the first 28 days on INC280 treatment
Category of DLTs	During the first 28 days on INC280 treatment
AUClast for INC280	Treatment Cycle 1 Day 1 (C1D1), C1D7, C1D15, C2D1, C3D1
AUCtau for INC280	C1D1, C1D7, C1D15, C2D1, C3D1
Cmax for INC280	C1D1, C1D7, C1D15, C2D1, C3D1
Tmax	C1D1, C1D7, C1D15, C2D1, C3D1

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events based on CTCAE grading and other safety variables (e.g. EGC readings, physical examination, vital signs and laboratory results).	Screening, until 30 days post-treatment

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Moreno V, Greil R, Yachnin J, Majem M, Wermke M, Arkenau HT, Basque JR, Nidamarthy PK, Kapoor S, Cui X, Giovannini M. Pharmacokinetics and safety of capmatinib with food in patients with MET-dysregulated advanced solid tumors. Clin Ther. 2021 Jun;43(6):1092-1111. doi: 10.1016/j.clinthera.2021.04.006. Epub 2021 May 27.

Helpful Links

• Results for CINC280A2108 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2016
• Primary Completion (Actual): May 16, 2018
• Study Completion (Actual): May 16, 2018

Study Registration Dates

• First Submitted: October 4, 2016
• First Submitted That Met QC Criteria: October 4, 2016
• First Posted (Estimate): October 5, 2016

Study Record Updates

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

More Information

Terms related to this study

• Keywords: cMET, INC280, food,
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CINC280A2108; 2016-001829-14 (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