Clinical Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (Geometry Mono-1)

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02414139

Collaborator

(none)

373

Enrollment

Locations

Arms

93.4

Anticipated Duration (Months)

3.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: INC280 (capmatinib)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

373 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II, Multicenter Study of Oral cMET Inhibitor INC280 in Adult Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC)(Geometry Mono-1)

Actual Study Start Date :

Jun 11, 2015

Anticipated Primary Completion Date :

Feb 7, 2023

Anticipated Study Completion Date :

Mar 23, 2023

Arms and Interventions

Arm	Intervention/Treatment
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)

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [at least 18 weeks]
Proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per RECIST 1.1

Secondary Outcome Measures

Duration of Response (DOR) - Key Secondary [at least 18 weeks]
Calculated as the time from the date of the first documented CR or PR by Blinded Independent Review Committee (BIRC) per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR.
Overall Response Rate (ORR) [at least 18 weeks]
ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment
Duration of Response (DOR) [at least 18 weeks]
DOR per RECIST 1.1 by investigator assessment
Time to Response (TTR) [at least 18 weeks]
TTR per RECIST 1.1 both by BIRC and investigator assessment
Disease Control Rate (DCR) [at least 18 weeks]
DCR per RECIST 1.1 both by BIRC and investigator assessment
Progression-free Survival (PFS) [at least 18 weeks]
PFS per RECIST 1.1 both by BIRC and investigator assessment
Overall Survival (OS) [at least 18 weeks]
OS, defined as time from first dose of INC280 to death due to any cause
Number of patients with incidence of adverse events and serious adverse events, change in vital signs, laboratory results (hematology, blood chemistry, and urinalysis) and ECG. [at least 18 weeks]
Safety of INC280
Cmax, Cmin and plasma concentration-time profiles of INC280 [6 weeks]
Pharmacokinetics of INC280 and metabolite CMN288

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pacific Shores Medical Group SC	Long Beach	California	United States	90813
2	UCLA Medical Center Dept of Onc	Los Angeles	California	United States	90095
3	University of California Irvine Medical Center Chao Family Chao Family Comp Cancer Center	Orange	California	United States	92868
4	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
5	University of Iowa Hospitals & Clinics SC-3	Iowa City	Iowa	United States	52242
6	Massachusetts General Hospital MGH Cancer Center	Boston	Massachusetts	United States	02114
7	VA Ann Arbor Health System VA Ann Arbor Health System	Ann Arbor	Michigan	United States	48105
8	Mayo Clinic	Rochester	Minnesota	United States	55905
9	Oregon Health and Science University SC	Portland	Oregon	United States	97239
10	Lehigh Valley Health Network SC	Allentown	Pennsylvania	United States	18103
11	Andrew and Patel Associates	Camp Hill	Pennsylvania	United States	17011
12	Cancer Therapy and Research Center UT Health Science Center SC-5	San Antonio	Texas	United States	78229
13	University of Utah / Huntsman Cancer Institute Oncology	Salt Lake City	Utah	United States	84103
14	Novartis Investigative Site	Caba	Buenos Aires	Argentina	C1426ANZ
15	Novartis Investigative Site	Buenos Aires	Caba	Argentina	C1431FWO
16	Novartis Investigative Site	La Rioja		Argentina	5300
17	Novartis Investigative Site	Wien		Austria	1210
18	Novartis Investigative Site	Leuven		Belgium	3000
19	Novartis Investigative Site	Marseille cedex 20	Bouches Du Rhone	France	13915
20	Novartis Investigative Site	Dijon Cedex	Cote D Or	France	21034
21	Novartis Investigative Site	Clermont-Ferrand		France	63011
22	Novartis Investigative Site	La Tronche		France	38700
23	Novartis Investigative Site	Lille		France	59000
24	Novartis Investigative Site	Marseille		France	13273
25	Novartis Investigative Site	Paris		France	75970
26	Novartis Investigative Site	Pierre Benite Cedex		France	69495
27	Novartis Investigative Site	Rennes		France	35043
28	Novartis Investigative Site	Strasbourg Cedex		France	67091
29	Novartis Investigative Site	Heidelberg	Baden-Württemberg	Germany	69126
30	Novartis Investigative Site	Koeln	Nordrhein-Westfalen	Germany	50937
31	Novartis Investigative Site	Berlin		Germany	13125
32	Novartis Investigative Site	Frankfurt		Germany	60590
33	Novartis Investigative Site	Gottingen		Germany	37075
34	Novartis Investigative Site	Halle (Saale)		Germany	06120
35	Novartis Investigative Site	Hamburg		Germany	20251
36	Novartis Investigative Site	Hannover		Germany	30625
37	Novartis Investigative Site	Homburg		Germany	66421
38	Novartis Investigative Site	Muenchen		Germany	81925
39	Novartis Investigative Site	Nuernberg		Germany	90419
40	Novartis Investigative Site	Ravensburg		Germany	88214
41	Novartis Investigative Site	Tübingen		Germany	72076
42	Novartis Investigative Site	Ulm		Germany	89081
43	Novartis Investigative Site	Ramat Gan		Israel	52621
44	Novartis Investigative Site	Tel Aviv		Israel	6423906
45	Novartis Investigative Site	Bologna	BO	Italy	40138
46	Novartis Investigative Site	Brescia	BS	Italy	25123
47	Novartis Investigative Site	Catania	CT	Italy	95124
48	Novartis Investigative Site	Catanzaro	CZ	Italy	88100
49	Novartis Investigative Site	Meldola	FC	Italy	47014
50	Novartis Investigative Site	Firenze	FI	Italy	50134
51	Novartis Investigative Site	Monza	MB	Italy	20900
52	Novartis Investigative Site	Milano	MI	Italy	20141
53	Novartis Investigative Site	Milano	MI	Italy	20162
54	Novartis Investigative Site	Modena	MO	Italy	41124
55	Novartis Investigative Site	Roma	RM	Italy	00155
56	Novartis Investigative Site	Verona	VR	Italy	37126
57	Novartis Investigative Site	Napoli		Italy	80131
58	Aichi Cancer Center Hospital	Nagoya City	Aichi	Japan	464-8681
59	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
60	National Cancer Center Hospital East	Kashiwa-City	Chiba	Japan	277-8577
61	National Kyushu Cancer Center	Minami-Ku	Fukuoka	Japan	811-1395
62	Hyogo Cancer Center	Akashi-city	Hyogo	Japan	673-8558
63	Sendai Kousei Hospital	Sendai-city	Miyagi	Japan	980-0873
64	Okayama University Hospital	Okayama-city	Okayama	Japan	700-8558
65	Kinki University Hospital	OsakaSayama-city	Osaka	Japan	589-8511
66	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
67	Novartis Investigative Site	Koto ku	Tokyo	Japan	135 8550
68	National Hospital Organization, Yamaguchi-Ube Medical Center	Ube-city	Yamaguchi	Japan	755-0241
69	Novartis Investigative Site	Bundang Gu	Gyeonggi Do	Korea, Republic of	13620
70	Novartis Investigative Site	Gyeonggi do	Korea	Korea, Republic of	10408
71	Novartis Investigative Site	Seoul		Korea, Republic of	03080
72	Novartis Investigative Site	Ashrafieh		Lebanon	166830
73	Novartis Investigative Site	Mexico	Distrito Federal	Mexico	14080
74	NKI-AVL, Department of Thoracic-Oncology	Amsterdam		Netherlands	1066 CX
75	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
76	Novartis Investigative Site	Maastricht		Netherlands	6229 HX
77	Novartis Investigative Site	Rotterdam		Netherlands	3015 GD
78	Novartis Investigative Site	Oslo		Norway	NO 0424
79	Novartis Investigative Site	Moscow		Russian Federation	109028
80	Novartis Investigative Site	Saint Petersburg		Russian Federation	192148
81	Novartis Investigative Site	Tambov		Russian Federation	392000
82	Novartis Investigative Site	Singapore		Singapore	119228
83	Novartis Investigative Site	Singapore		Singapore	169610
84	Novartis Investigative Site	Sevilla	Andalucia	Spain	41017
85	Novartis Investigative Site	Oviedo	Asturias	Spain	33011
86	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
87	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
88	Novartis Investigative Site	La Coruna	Galicia	Spain	15006
89	Novartis Investigative Site	Madrid		Spain	28034
90	Novartis Investigative Site	Madrid		Spain	28041
91	Novartis Investigative Site	Stockholm		Sweden	SE-171 76
92	Novartis Investigative Site	Kaohsiung		Taiwan	82445
93	Novartis Investigative Site	Taipei		Taiwan	10002
94	Novartis Investigative Site	Taoyuan		Taiwan	33305
95	Novartis Investigative Site	Birmingham		United Kingdom	B9 5SS
96	Novartis Investigative Site	London		United Kingdom	W6 8RF