Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer

Purpose

A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) as measured by overall response rate (ORR). The study will also evaluate safety and pharmacokinetics of INC280.

Condition

  • Carcinoma, Non-Small-Cell Lung

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Stage IIIB or IV NSCLC (any histology) at the time of study entry
  • Histologically or cytologically confirmed diagnosis of NSCLC that is:
  • EGFR wt as per patient standard of care by a validated test
  • AND ALK-negative rearrangement as part of the patient standard of care by a validated test
  • AND (by central assessment) either:
  • Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or
  • Cohort 2: Pre-treated patients with cMET GCN ≥4 and < 6, or
  • Cohort 3: Pre-treated patients with cMET GCN < 4, or
  • Cohort 4: Pre-treated patients with cMET mutations regardless of cMET GCN, or
  • Cohort 5: Treatment-naïve patients with cMET dysregulation, or
  • Cohort 6: Pre-treated patients with either cMET GCN ≥ 10 without cMET mutations or cMET mutations regardless of cMET GCN, or
  • Cohort 7: Treatment-naïve patients with cMET mutations regardless of cMET GCN
  • To be eligible for Cohorts 1-4, patients must have failed one or two prior lines of systemic therapy for advanced/metastatic disease
  • To be eligible for Cohort 6, patients must have failed one prior line of systemic therapy for advanced/metastatic disease
  • To be eligible for Cohort 5 and Cohort 7, patients must not have received any systemic therapy for advanced/metastatic disease
  • At least one measurable lesion as defined by RECIST 1.1
  • Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter the study.
  • Patients must have adequate organ function
  • ECOG performance status (PS) of 0 or 1 Details and other protocol-defined inclusion criteria may apply

Exclusion Criteria

  • Prior treatment with crizotinib, or any other cMET or HGF inhibitor
  • Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy, including, but not limited to exon 19 deletions and exon 21 mutations
  • Patients with characterized ALK-positive rearrangement
  • Clinically significant, uncontrolled heart diseases.
  • Patients receiving treatment with medications that cannot be discontinued at least 1 week prior to first INC280 treatment and for the duration of the study:
  • Strong inducers of CYP3A4
  • Impairment of GI function or GI disease that may significantly alter the absorption of INC280
  • Patients receiving treatment with any enzyme-inducing anticonvulsant
  • Applicable to Cohorts 1-4 and Cohort 6 only: Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of the agent (whichever is longer) before first dose
  • Pregnant or nursing women
  • Women of child-bearing potential, unless they are using highly effective methods of contraception
  • Sexually active males unless they use a condom during intercourse
  • Presence or history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis

Other protocol-defined exclusion criteria may apply

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
cMET GCN ≥ 6
Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID as second or third line
  • Drug: INC280 (capmatinib)
Experimental
cMET GCN ≥ 4 and < 6
Pre-treated patients with cMET GCN ≥ 4 and < 6 treated with INC280 at 400 mg BID as second or third line
  • Drug: INC280 (capmatinib)
Experimental
cMET GCN < 4
Pre-treated patients with cMET GCN < 4 treated with INC280 at 400mg BID as second or third line
  • Drug: INC280 (capmatinib)
Experimental
cMET mutations
Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID as second or third line
  • Drug: INC280 (capmatinib)
Experimental
cMET dysregulation - treatment-naïve
Treatment-naïve patients with cMET dysregulation treated with INC280 at 400mg BID
  • Drug: INC280 (capmatinib)
Experimental
cMET dysregulation - second line
Pre-treated patients with cMET deregulation treated with INC280 at 400 mg BID as second line
  • Drug: INC280 (capmatinib)
Experimental
cMET mutations treatment-naïve
Treatment-naïve patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID
  • Drug: INC280 (capmatinib)

Recruiting Locations

University of Arkansas for Medical Science SC
Little Rock, Arkansas 72205
Contact:
Kathryn Allen
+501 526 6990 ext 8026
KGAllen@uams.edu

Pacific Shores Medical Group SC
Long Beach, California 90813
Contact:
Victoria Lansang
victorial@pacshoresoncology.com

Los Angeles Hematology/Oncology Medical Group
Los Angeles, California 90017
Contact:
Elizabeth Tica
213-977-1214
elizabeth.tica@lahomg.com

VA Comprehensive Cancer Center
West Haven, Connecticut 06516
Contact:
Sara Turek
Sara.turek@va.gov

Georgetown University Lombardi Cancer Center
Washington, District of Columbia 20007 2197
Contact:
202-687-9861

H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida 33612
Contact:
Thanh L. Phan
888-663-3488
tphan@uci.edu

Emory University School of Medicine/Winship Cancer Institute SC-2
Atlanta, Georgia 30322
Contact:
Ellie Butler
404-778-4576
Ellie.Butler@emory.edu

Northwest Georgia Oncology Centers, P.C.,
Marietta, Georgia 30060
Contact:
Feseha Makonnen
770-281-5100
fmakonnen@gnoc.com

Decatur Memorial Hospital
Decatur, Illinois 62526
Contact:
Cindy Albright
217-876-6609
calbright@dmhhs.org

University of Iowa Hospitals & Clinics SC-3
Iowa City, Iowa 52242

Massachusetts General Hospital MGH Cancer Center
Boston, Massachusetts 02114
Contact:
Caitlyn Helms
chelms@mgh.harvard.edu

Boston VA Healthcare Boston VA
Boston, Massachusetts 02131
Contact:
Corri Dedomenico
+1 617 617 632 5607
Corri.Dedomenico@va.gov

VA Ann Arbor Health System VA Ann Arbor Health System
Ann Arbor, Michigan 48105
Contact:
Sara Turek
Sara.turek@va.gov

Karmanos Cancer Institute
Detroit, Michigan 48201
Contact:
Deborah Hackstock
313-576-9454
hackstod@karmanos.org

Henry Ford Hospital SC
Detroit, Michigan 48202-2689
Contact:
Jennifer M Carabio
313-916-1784
jcarbi@hfhs.org

Minneapolis VA Medical Center
Minneaplois, Michigan 55417
Contact:
Sara Turek
Sara.turek@va.gov

Mayo Clinic
Rochester, Minnesota 55905
Contact:
Ann Marie Mayer
507-538-6646
mayer.annmarie@mayo.edu

St. Luke's Cancer Institute SC-2
Kansas City, Missouri 64111
Contact:
Jessica Yingling
816-932-2677
jyingling@saint-lukes.org

VA Nebraska-Western Iowa Health Care System
Omaha, Nebraska 68105
Contact:
Holly DeSpiegelaere
402-995-3330
Holly.despiegelaere@va.fov

Dartmouth Hitchcock Medical Center SC
Lebanon, New Hampshire 03756
Contact:
Crystallee Newton
603-650-4428
Crystallee.J.Newton@Hitchcock.org

Roswell Park Cancer Institute Rosewell
Buffalo, New York 14263
Contact:
Kelly Dunn
716-845-4886
kelly.dunn@roswellpark.org

Durham VA Medical Center Durham VA Med Ctr -Station 558
Durham, North Carolina 27705
Contact:
Sara Turek
Sara.turek@va.gov

Oregon Health and Science University SC
Portland, Oregon 97239
Contact:
Investigational Pharmacy
503-418-9736
invdrugs@ohsu.edu

Lehigh Valley Health Network SC
Allentown, Pennsylvania 18103
Contact:
Trina M Grace
610-402-0546
trina_b.grace@lvh.com

Andrew & Patel Associates,
Camp Hill, Pennsylvania 17011
Contact:
Renee Kessler
717-761-8740
rkessler@andrewspatel.com

GHS Cancer Intitute
Greenville, South Carolina 29615
Contact:
Melanie Mayes
864-242-2762
Mmayes2@ghs.org

Sarah Cannon Research Institute Sarah Cannon Cancer Center
Nashville, Tennessee 37203
Contact:
Julie W. Trundle
615-329-7484
Julie.trundle@scresearch.net

Cancer Therapy & Research Center UT Health Science Center SC-5
San Antonio, Texas 78229
Contact:
Tyson DeSutter
desutter@uthscsa.edu

University of Utah / Huntsman Cancer Institute Oncology
Salt Lake City, Utah 84103
Contact:
Natalie Graves
801-585-0443
Natalie.graves@hci.utah.edu

Virginia Cancer Specialists Virginia Cancer Specialists
Fairfax, Virginia 22031
Contact:
Monica Cochrane
monica.cochrane@usoncology.com

More Details

NCT ID
NCT02414139
Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com