TRIDENT-1: A Study of Repotrectinib (TPX-0005) in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements

Sponsor

Turning Point Therapeutics, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03093116

Collaborator

Zai Lab (Shanghai) Co., Ltd. (Industry)

500

Enrollment

175

Locations

Arm

75.1

Anticipated Duration (Months)

2.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Phase 1 dose escalation will determine the first cycle dose-limiting toxicities (DLTs), the maximum tolerated dose (MTD), the biologically effective dose and recommended Phase 2 dose (RP2D) of repotrectinib given to adult subjects with advanced solid malignancies harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.

Midazolam DDI substudy will examine effect of of repotrectinib on CYP3A induction.

Phase 2 will determine the confirmed Overall Response Rate (ORR) as assessed by Blinded Independent Central Review (BICR) of repotrectinib in each subject population expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement. The secondary objective will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) of repotrectinib in each expansion cohort of advanced solid tumors that harbor a ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement.

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Solid Tumors Metastatic Solid Tumors	Drug: Oral repotrectinib (TPX-0005)	Phase 1/Phase 2

Detailed Description

In Phase 2, study subjects will be enrolled into 6 distinct expansion (EXP) cohorts:

EXP-1: ROS1 TKI-naïve ROS1+ NSCLC. Up to one prior line of chemotherapy OR immunotherapy is allowed
EXP-2: 1 Prior ROS1 TKI AND 1 Platinum-based Chemotherapy ROS1+ NSCLC. Disease progression, or intolerant to one prior line of a ROS1 TKI. Must have received one prior line of platinum based chemotherapy OR one prior line of platinum based chemotherapy in combination with immunotherapy before or after a ROS1 TKI
EXP-3: 2 Prior ROS1 TKIs AND NO Chemotherapy ROS1+ NSCLC. Disease progression, or intolerant to 2 prior lines of a ROS1 TKI treatment. No prior lines of chemotherapy or immunotherapy are allowed.
EXP-4: 1 Prior ROS1 TKI and NO Chemotherapy or Immunotherapy. Disease progression or intolerant to one prior line of a ROS1 TKI. No prior lines of chemotherapy or immunotherapy are allowed.
EXP-5: TRK TKI-naïve NTRK+ solid tumors. Any number of prior lines of chemo or immunotherapy is allowed.
EXP-6: TRK TKI-pretreated NTRK+ solid tumors. Disease progression, or intolerant to 1 or 2 prior TRK TKIs. Any number of prior lines of chemo- or immunotherapy are allowed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2, Open-Label, Multi-Center, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of TPX-0005 in Patients With Advanced Solid Tumors Harboring ALK, ROS1, or NTRK1-3 Rearrangements (TRIDENT-1)

Actual Study Start Date :

Feb 27, 2017

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Repotrectinib (TPX-0005) Phase 1 Oral repotrectinib (TPX-0005): Phase 1a dose escalation, Phase 1b food-effect sub-study, and Phase 1c dose escalation with food, and Midazolam drug-drug interaction sub-study. Phase 2 Oral repotrectinib (TPX-0005): 6 distinct expansion cohorts EXP-1: ROS1 TKI-naïve ROS1+ NSCLC EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) EXP-5: TRK TKI-naïve NTRK+ solid tumors EXP-6: TRK TKI-pretreated NTRK+ solid tumors	Drug: Oral repotrectinib (TPX-0005) Oral repotrectinib (TPX-0005) capsules. Other Names: repotrectinib

Arm

Intervention/Treatment

Experimental: Repotrectinib (TPX-0005)

Phase 1 Oral repotrectinib (TPX-0005): Phase 1a dose escalation, Phase 1b food-effect sub-study, and Phase 1c dose escalation with food, and Midazolam drug-drug interaction sub-study. Phase 2 Oral repotrectinib (TPX-0005): 6 distinct expansion cohorts EXP-1: ROS1 TKI-naïve ROS1+ NSCLC EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) EXP-5: TRK TKI-naïve NTRK+ solid tumors EXP-6: TRK TKI-pretreated NTRK+ solid tumors

Drug: Oral repotrectinib (TPX-0005)

Oral repotrectinib (TPX-0005) capsules.

Other Names:

repotrectinib

Outcome Measures

Primary Outcome Measures

Dose limiting toxicities (DLTs) (Phase 1) [Within 28 days of the first repotrectinib dose]
Define the dose limiting toxicities (DLTs) (Phase 1)
Recommended Phase 2 Dose (RP2D) (Phase 1) [Within 28 days of the last patient dosed in escalation]
To determine the RP2D (Phase 1)
Overall Response Rate (ORR) Phase 2 [Two to three years after first dose of repotrectinib dose]
To determine the confirmed ORR of repotrectinib (TPX-0005) as assessed by Blinded Independent Central Review (Phase 2)

Secondary Outcome Measures

Maximum plasma concentration (CMAX) of repotrectinib (TPX-0005) (Phase 1) [Up to 72 hours post dose]
To determine the maximum plasma concentration (CMAX) of repotrectinib (TPX-0005)
Area under the plasma concentration time curve (AUC) of repotrectinib (TPX-0005) (Phase 1) [Up to 72 hours post dose]
To determine the area under the plasma concentration time curve (AUC) of repotrectinib
Area under the plasma concentration time curve (AUC) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1) [Up to 72 hours post dose]
To determine the area under the plasma concentration time curve (AUC) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)
Maximum plasma concentration (CMAX) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1) [Up to 72 hours post dose]
To determine the maximum plasma concentration (CMAX) of repotrectinib under different food intake conditions(TPX-0005) (Phase 1)
Area under the plasma concentration time curve (AUC) of midazolam(TPX-0005) (Phase 1) [Up to 24 hours post dose]
To determine the area under the plasma concentration time curve (AUC) of midazolam(TPX-0005) (Phase 1)
Maximum plasma concentration (CMAX) of midazolam(TPX-0005) (Phase 1) [Up to 24 hours post dose]
To determine the maximum plasma concentration (CMAX) of midazolam(TPX-0005) (Phase 1)
Plasma concentration of repotrectinib following administration at RP2D (Phase 2) [Pre dose and 4 hours post dose]
To evaluate the plasma concentration of repotrectinib following administration at RP2D (Phase 2)
Preliminary objective response rate (ORR) (Phase 1) [Approximately three years]
To determine the preliminary objective response rate (ORR) by Blinded Independent Central Review (BICR) (Phase 1)
Duration of response (DOR) (Phase 2) [Approximately three years]
To determine the DOR of repotrectinib (TPX-0005) (Phase 2)
Clinical benefit rate (CBR) (Phase 2) [Approximately three years]
To determine the CBR of repotrectinib (TPX-0005) (Phase 2)
Progression free survival (PFS) (Phase 2) [Approximately three years]
To determine the PFS (Phase 2)
Overall survival (OS) (Phase 2) [Approximately three years]
To determine the OS (Phase 2)
Intracranial objective response rate (Phase 2) [Approximately three years]
To determine the intracranial objective response rate (Phase 2)

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

PHASE 1

Key Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) (Stage IV, American Joint Committee on Cancer v.7) that harbors an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement by protocol specified tests.
ECOG PS 0-1.
Age ≥18 (or age ≥ 20 of age as required by local regulation).
Capability to swallow capsules intact (without chewing, crushing, or opening).
At least 1 measurable target lesion according to RECIST version 1.1. CNS-only measurable disease as defined by RECIST version 1.1 is allowed.
Prior cytotoxic chemotherapy is allowed.
Prior immunotherapy is allowed.
Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
Patients with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance Within normal limits or > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
Life expectancy ≥ 3 months.

PHASE 2 Key Inclusion Criteria

Histologically or cytologically confirmed diagnosis of locally advanced, or metastatic solid tumor (including primary CNS tumors) that harbors a ROS1, or NTRK1-3 gene fusion.
Subject must have a documented ROS1 or NTRK1-3 gene fusion determined by tissue-based local testing using either:
a next-generation sequencing (NGS) or quantitative polymerase chain reaction (qPCR) test will be accepted to determine molecular eligibility.

• Adequate tumor tissue needs to be sent to the Sponsor designated central diagnostic laboratory for retrospective confirmation by a central diagnostic laboratory test selected by the Sponsor.

a fluorescence in situ hybridization (FISH) test AND prospective confirmation of fusion status by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment will be accepted to determine molecular eligibility.

Adequate tumor tissue must be sent to the Sponsor designated central diagnostic laboratory for prospective confirmation by a central diagnostic laboratory test selected by the Sponsor PRIOR to enrollment.

Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
Age ≥12 (or age ≥ 20 as required by local regulation).
Willing and able to provide written institutional review board (IRB)/institutional ethics committee-approved Informed Consent or an Assent signed by a parent or legal guardian for subjects age 12 to 17.
At least 1 measurable target lesion according to RECIST (v1.1) prospectively confirmed by Blinded Independent Central Radiology Review (BICR), selected by Sponsor, PRIOR to enrollment. Subjects with CNS-only measurable disease ≥10 mm as defined by RECIST (v1.1) are eligible.
Subjects with advanced solid tumors harboring ROS1, NTRK1, NTRK2, or NTRK3 rearrangement will be assigned into 6 distinct expansion (EXP) cohorts provided all inclusion and exclusion criteria are met.

EXP-1: ROS1 TKI-naïve ROS1+ NSCLC ii. EXP-2: 1 Prior ROS1 TKI and 1 Platinum based chemo ROS1+ NSCLC iii. EXP-3: 2 Prior ROS1 TKIs ROS1+ NSCLC (No Chemo or IO) iv. EXP-4: 1 Prior ROS1 TKI ROS1+ NSCLC (No Chemo or IO) v. EXP-5: TRK TKI-naïve NTRK+ solid tumors vi. EXP-6: TRK TKI-pretreated NTRK+ solid tumors

Subjects with asymptomatic CNS metastases (treated or untreated) and/or asymptomatic leptomeningeal carcinomatosis are eligible to enroll if they satisfy the protocol specified criteria.
Baseline laboratory values fulfilling the following requirements:Absolute neutrophils count (ANC) ≥1500/mm3 (1.5 × 109/L); Platelets (PLTs) ≥100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.0 g/dL transfusions are allowed; Serum creatinine or creatinine clearance > 40 mL/min; Total serum bilirubin < 1.5 × ULN; Liver transaminases (ASTs/ALTs) < 2.5 × ULN; < 5 × ULN if liver metastases are present Alkaline phosphatase (ALP); < 2.5 × ULN; < 5 × ULN if liver and/or bone metastasis are present; Serum calcium, magnesium, and potassium Normal or CTCAE grade ≤ 1 with or without supplementation
Life expectancy ≥ 3 months.

Key Exclusion Criteria PHASE 1 and PHASE 2

Concurrent participation in another therapeutic clinical trial.
Symptomatic brain metastases or leptomeningeal involvement.
History of previous cancer, except for squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected, requiring therapy within the previous 2 years.
Major surgery within 4 weeks of start of repotrectinib treatment. Radiation therapy (except palliative to relieve bone pain) within 2 weeks of study entry. Palliative radiation (≤10 fractions) must have been completed at least 48 hours prior to study entry
Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class ≥ II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2
Any of the following cardiac criteria:

Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTcF) > 470 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval > 250 msec) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval.

Known active infections (bacterial, fungal, viral including HIV positivity).
Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
Peripheral neuropathy of CTCAE ≥grade 2.
History of extensive, disseminated, bilateral, or presence of CTCAE grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. Subjects with history of prior radiation pneumonitis are not excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yuma Regional Medical Center PHASE 2	Yuma	Arizona	United States	85364
2	City of Hope PHASE 2	Duarte	California	United States	91010
3	Adventist Health Glendale PHASE 2	Glendale	California	United States	91206
4	MemorialCare Long Beach PHASE 2	Long Beach	California	United States	90806
5	Pacific Shores Oncology PHASE 2	Long Beach	California	United States	90813
6	UC Irvine Health, Chao Family Comprehensive Cancer Center PHASE 1 (recruiting) & PHASE 2 (recruiting)	Orange	California	United States	92868
7	Ventura County Hematology Oncology Specialists PHASE 2	Oxnard	California	United States	93030
8	UC San Diego Moores Cancer Center PHASE 2	San Diego	California	United States	92093
9	St Joseph's Heritage Healthcare PHASE 2	Santa Rosa	California	United States	95403
10	University of Colorado Denver PHASE 1 (recruiting) & PHASE 2 (recruiting)	Aurora	Colorado	United States	80045
11	Georgetown Lombardi Comprehensive Cancer Center PHASE 2	Washington	District of Columbia	United States	20007
12	Johns Hopkins Kimmel Cancer Center PHASE 2	Washington	District of Columbia	United States	20016
13	Memorial Healthcare System PHASE 2	Hollywood	Florida	United States	33021
14	Cancer Specialists of North Florida PHASE 2	Jacksonville	Florida	United States	32256
15	Ocala Oncology PHASE 2	Ocala	Florida	United States	34474
16	Moffitt Cancer Center PHASE 2	Tampa	Florida	United States	33612
17	University Cancer and Blood Center PHASE 2	Athens	Georgia	United States	30607
18	Columbus Regional Research Institute PHASE 2	Columbus	Georgia	United States	31904
19	Hawaii Cancer Care PHASE 2	Honolulu	Hawaii	United States	96813
20	University of Chicago PHASE 2	Chicago	Illinois	United States	60637
21	Illinois Cancer Care PHASE 2	Peoria	Illinois	United States	61615
22	Fort Wayne Medical Oncology and Hematology PHASE 2	Fort Wayne	Indiana	United States	46845
23	Beacon Health PHASE 2	South Bend	Indiana	United States	46601
24	Pontchartrain Cancer Center (QCCA) PHASE 2	Covington	Louisiana	United States	70433
25	University of Maryland School of Medicine PHASE 2	Baltimore	Maryland	United States	21201
26	The Center for Cancer & Blood Disorders - Maryland PHASE 2	Bethesda	Maryland	United States	20817
27	Frederick Health - James M Stockman Cancer Institute PHASE 2	Frederick	Maryland	United States	21702
28	Massachusetts General Hospital PHASE 1 (recruiting) & PHASE 2 (recruiting)	Boston	Massachusetts	United States	02114
29	MGH Satellite - Dana-Farber Cancer Institute PHASE 2	Boston	Massachusetts	United States	02215
30	Southcoast PHASE 2	Fairhaven	Massachusetts	United States	02719
31	University of Michigan Rogel Cancer Center PHASE 2	Ann Arbor	Michigan	United States	48109
32	Karmanos Cancer Institute PHASE 2	Detroit	Michigan	United States	48201
33	Henry Ford Health System PHASE 2	Detroit	Michigan	United States	48202
34	Sparrow Health System PHASE 2	Lansing	Michigan	United States	48912
35	Regions Hospital Cancer Care Center PHASE 2	Saint Paul	Minnesota	United States	55101
36	Central Care Cancer Center PHASE 2	Bolivar	Missouri	United States	65613
37	Mosaic Life Care PHASE 2	Saint Joseph	Missouri	United States	64507
38	Washington University Siteman Cancer Center PHASE 2	Saint Louis	Missouri	United States	63110
39	New Jersey Cancer Care and Blood Disorders PHASE 2	Belleville	New Jersey	United States	07109
40	Summit Medical Group PHASE 2	Berkeley Heights	New Jersey	United States	07932
41	Rutgers Cancer Institute PHASE 2	New Brunswick	New Jersey	United States	08901
42	NYU Langone Health PHASE 2	New York	New York	United States	10016
43	Memorial Sloan Kettering Cancer Center PHASE 1 (recruiting) & PHASE 2 (Recruiting)	New York	New York	United States	10065
44	Southeastern Medical Oncology Center PHASE 2	Goldsboro	North Carolina	United States	27534
45	Gabrail Cancer Center PHASE 2	Canton	Ohio	United States	44718
46	TriHealth Cancer Institute PHASE 2	Cincinnati	Ohio	United States	45220
47	Cleveland Clinic PHASE 2	Cleveland	Ohio	United States	44195
48	Ohio State Wexner Medical Center PHASE 2	Columbus	Ohio	United States	43210
49	OhioHealth PHASE 2	Columbus	Ohio	United States	43214
50	University of Toledo PHASE 2	Toledo	Ohio	United States	22031
51	Oklahoma Cancer Specialists and Research Institute Tulsa, OK (OCSRI) (QCCA) PHASE 2	Tulsa	Oklahoma	United States	74146
52	Gettysburg PHASE 2	Gettysburg	Pennsylvania	United States	17325
53	Fox Chase Cancer Center PHASE 2	Philadelphia	Pennsylvania	United States	19111
54	Sanford Health PHASE 2	Sioux Falls	South Dakota	United States	57104
55	Avera Cancer Institute Center for Precision Oncology PHASE 2	Sioux Falls	South Dakota	United States	57105
56	UT Southwestern Medical Center PHASE 2	Dallas	Texas	United States	75390
57	MD Anderson Cancer Center - The University of Texas PHASE 2	Houston	Texas	United States	77030
58	Oncology Consultants P.A. PHASE 2	Houston	Texas	United States	77030
59	Lumi Research PHASE 2	Kingwood	Texas	United States	77339
60	Utah Cancer Specialists PHASE 2	Salt Lake City	Utah	United States	84106
61	Virginia Cancer Specialists PHASE 2	Fairfax	Virginia	United States	22031
62	Hematology Oncology Associates of Fredericksburg PHASE 2	Fredericksburg	Virginia	United States	22408
63	PeaceHealth - Bellingham (NW) PHASE 2	Bellingham	Washington	United States	98225
64	UW Seattle Cancer Care Alliance PHASE 2	Seattle	Washington	United States	98109
65	ThedaCare PHASE 2	Appleton	Wisconsin	United States	54911
66	The Chris O-Brien Lifehouse PHASE 2	Camperdown	New South Wales	Australia	2050
67	Flinders Medical Centre PHASE 2	Bedford Park	South Australia	Australia	5042
68	Peter MacCallum Cancer Center PHASE 2	Melbourne	Victoria	Australia	3501
69	UZA Research Unit Oncology- route 55 PHASE 2	Edegem		Belgium	B-2650
70	UZ Leuven - Campus Gasthuisberg PHASE 2	Leuven		Belgium	B-3000
71	Cross Cancer Institute PHASE 2	Edmonton	Alberta	Canada	T6G 1Z2
72	BC Cancer PHASE 2	Vancouver	British Columbia	Canada	V5Z 4E11
73	William Osler Health System PHASE 2	Brampton	Ontario	Canada	L6R 37R
74	The Ottawa Hospital PHASE 2	Ottawa	Ontario	Canada	K1H 8L6
75	Princess Margaret Cancer Center at University Health Network PHASE 2	Toronto	Ontario	Canada	M5G 2C1
76	Anhui Provincial Hospital/Oncology Department PHASE 2	Hefei	Anhui	China
77	Cancer Hospital Chinese Academy of Medical Sciences/Cancer Institute PHASE 2	Chaoyang	Beijing	China
78	Beijing Cancer Hospital/Oncology Department PHASE 2	Haidian	Beijing	China
79	West China Hospital Sichuan University/Lung cancer center PHASE 2	Wenjiang	Chengdu	China
80	Daping Hospital, the Third Affiliated Hospital of Third Military Medical University /Cancer Center PHASE 2	Daping	Chongqing	China
81	The first Hospital Affiliated to AMU (Southwest Hospital)/Pneumology Department PHASE 2	Shapingba	Chongqing	China
82	The First Affiliated Hospital of Xiamen University/Medical oncology Department PHASE 2	Fujian	Fujian	China
83	Fujian Provincial Cancer Hospital/Thoracic oncology Department PHASE 2	Fuzhou	Fujian	China
84	Guangdong Provincial People's Hospital PHASE 2	Guangzhou	Guangdong	China
85	The Affiliated Tumor Hospital of Harbin Medical University/Medical Oncology Department PHASE 2	Heilongjiang	Heilongjiang	China
86	Henan Cancer Hospital/The 1st pneumology department PHASE 2	Zhengzhou	Henan	China
87	Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology/Cancer Center Department PHASE 2	Wuhan	Hubei	China
88	The Second XIANGYA Hospital Of Central South University/Oncology Department PHASE 2	Changsha	Hunan	China
89	The Third Xiangya Hospital of Central South University/Department of Respiratory and Critical Care Medicine PHASE 2	Changsha	Hunan	China
90	Nanjing Drum Tower Hospital PHASE 2	Nanjing	Jiangsu	China
91	XuZhou Central Hospital/Oncology Department PHASE 2	Xuzhou	Jiangsu	China
92	Jilin Cancer Hospital/Medical Oncology Department PHASE 2	Jilin	Jilin	China
93	The First Hospital of Jilin University/Oncology Center Department PHASE 2	Jilin	Jilin	China
94	Liaoning Cancer hospital PHASE 2	Shenyang	Liaoning	China
95	Jinan Central Hospital/Medical Oncology Department PHASE 2	Shandong	Shandong	China
96	Weifang People's Hospital/Medical Oncology Department PHASE 2	Shandong	Shandong	China
97	Shanghai Chest Hospital/Chest Cancer Institute PHASE 2	Shanghai	Shanghai	China
98	Shanghai Chest Hospital/Oncology Department PHASE 2	Shanghai	Shanghai	China
99	Shanxi Bethune Hospital PHASE 2	Shanxi	Shanxi	China
100	Tangdu Hospital PHASE 2	Shanxi	Shanxi	China
101	Sichuan Cancer Hospital/Medical Oncology Department PHASE 2	Sichuan	Sichuan	China
102	Hunan Cancer Hospital/Medical Oncology Department PHASE 2	Yuelu	Yuelu	China
103	The First Affiliated Hospital of Gannan Medical University PHASE 2	Zhanggong	Zhanggong	China
104	Sir Run Run Shaw Hospital Zhejiang University School of Medicine/Oncology Department PHASE 2	Hangzhou	Zhejiang	China
105	Zhejiang Cancer Hospital/Thoracic Oncology Department PHASE 2	Hangzhou	Zhejiang	China
106	The First Affiliated Hospital Zhejiang University School of Medicine/Respiratory medicine Department PHASE 2	Zhejiang	Zhejiang	China
107	Rigshospitalet, University Hospital of Copenhagen PHASE 2	Copenhagen		Denmark	2100
108	Centre Hospitalier Regional Vuniversitaire Brest PHASE 2	Brest		France	29200
109	Centre Georges-Francois PHASE 2	Dijon		France	21079
110	Centre Hospitalier Universitarie Arie Grenoble Alpes (CHUGA) PHASE 2	Grenoble		France	38043
111	Hospital de la Timone PHASE 2	Marseille		France	13005
112	Centre Antoine Lacassagne Phase 2	Nice		France	06189
113	CHU Poitiers PHASE 2	Poitiers		France	86000
114	Hopital D'Instruction Des Armees Begin PHASE 2	Saint-Mandé		France	94160
115	Institut Gustave Roussy PHASE 2	Villejuif		France	94805
116	Evangelische Lungenklinik Berlin PHASE 2	Berlin		Germany	13125
117	Centrum für Integrierte Onkologie - Universitaetsklinikum Koeln PHASE 2	Cologne		Germany	50937
118	University Clinic Carl Gustav Carus PHASE 2	Dresden		Germany	01307
119	University Hospital Heidelberg PHASE 2	Heidelberg		Germany
120	Queen Mary Hospital PHASE 2	Hong Kong		Hong Kong
121	Queen Mary Hospital PHASE 2	Hong Kong		Hong Kong
122	Hong Kong United Oncology Centre PHASE 2	Kowloon		Hong Kong
123	Prince of Wales Hospital PHASE 2	Sha Tin		Hong Kong
124	Semmelweis Egyetem PHASE 2	Budapest		Hungary	1083
125	Országos Korányi TBC és Pulmonológiai Intézet Budapest PHASE 2	Budapest		Hungary	1121
126	Centro Di Riferimento PHASE 2	Aviano		Italy	33081
127	Fondazione IRCCS CA Granda Ospedale Maggiore Policlinico PHASE 2	Milan		Italy	20122
128	Fondazione IRCCS Istituto Nazionale Dei Tumori PHASE 2	Milan		Italy	20133
129	Azienda Ospedaliera Ospedali Riuniti "Villa Sofia - Cerevello" PHASE 2	Palermo		Italy
130	Arcispedale S. Maria Nuova PHASE 2	Reggio Emilia		Italy	42123
131	IRCCS Istituto Regina Elena Oncologia Medica 1 PHASE 2	Roma		Italy	144
132	Azienda Ospedaliera Santa Maria di Terni - PHASE 2	Terni		Italy	5100
133	Nagoya University Hospital PHASE 2	Nagoya-shi	Aichi	Japan	466-8560
134	National Cancer Center Hospital East PHASE 2	Kashiwa	Chiba	Japan	277-8577
135	Ehime University PHASE 2	Toon-shi	Ehime	Japan	791-0295
136	Hokkaido University Hospital PHASE 2	Sapporo-shi	Hokkaido	Japan	060-8648
137	Kanagawa Cancer Center, Yokohama PHASE 2	Yokohama-shi	Kanagawa	Japan	241-8515
138	Osaka City General Hospital PHASE 2	Osaka-shi	Osaka	Japan	534-0021
139	Osaka International Cancer Institute PHASE 2	Osaka-shi	Osaka	Japan	541-8567
140	National Cancer Center Hospital, Tokyo PHASE 2	Chuo-ku	Tokyo	Japan	104-0045
141	Tottori University Hospital PHASE 2	Yonago-shi	Tottori	Japan	683-8504
142	Chungbuk National University Hospital PHASE 2	Cheongju-si	Chungcheongbuk-do	Korea, Republic of	28644
143	Chonnam National University Hwasun Hospital PHASE 2	Hwasun	Jeollanam-do	Korea, Republic of	58128
144	Seoul National University Hospital PHASE 2	Seoul		Korea, Republic of	03080
145	Konkuk University Medical Center PHASE 2	Seoul		Korea, Republic of	05030
146	Asan Medical Center PHASE 2	Seoul		Korea, Republic of	05505
147	Samsung Medical Center PHASE 2	Seoul		Korea, Republic of	06351
148	Seoul Saint Mary's Hospital PHASE 2	Seoul		Korea, Republic of	06591
149	Seoul National University Hospital PHASE 1 (recruiting) and PHASE 2 (not yet recruiting)	Seoul		Korea, Republic of	110-744
150	Yonsei Cancer Center, Severance Hospital PHASE 1 (recruiting) & PHASE 2 (recruiting)	Seoul		Korea, Republic of	120-752
151	Samsung Medical Center PHASE 1	Seoul		Korea, Republic of	135-710
152	Netherlands Cancer Institute PHASE 2	Amsterdam		Netherlands	1066 CX
153	Universiair Medisch Centrum Groningen PHASE 2	Groningen		Netherlands	9713 GZ
154	Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii PHASE 2	Gdańsk		Poland	80-214
155	Katedra i Klinika Pneumonologii, Onkologii i Alergologii Uniwersytetu Medycznego w Lublinie PHASE 2	Lublin		Poland	20-609
156	Med Polonia, ul. Obornicka PHASE 2	Poznan		Poland	60693
157	Centrum Medyczne Dom Lekarski PHASE 2	Szczecin		Poland	70784
158	Maria Sklodowska-Curie Cancer Centre and Institute PHASE 2	Warszawa		Poland	02-781
159	National University Hospital PHASE 2	Singapore	Central Singapore	Singapore	119704
160	National Cancer Center Singapore PHASE 2	Singapore	Central Singapore	Singapore	169610
161	Clinica Universidad de Navarra PHASE 2	Pamplona	Navarra	Spain	31008
162	Hospital Universitario Dexeus - Grupo Quironsalud PHASE 2	Barcelona		Spain	08028
163	Vall d'Hebron University Hospital PHASE 2	Barcelona		Spain	08035
164	Fundacion MD Anderson PHASE 2	Madrid		Spain	28033
165	START Madrid-FJD PHASE 2	Madrid		Spain	28040
166	Hospital Universitario 12 de Octubre PHASE 2	Madrid		Spain	28041
167	Hospital HM Sanchinarro PHASE 2	Madrid		Spain	28050
168	Instituto Valenciano de Oncología PHASE 2	Valencia		Spain	46009
169	National Cheng Kung University Hospital PHASE 2	Tainan		Taiwan	704
170	National Taiwan University Hospital PHASE 2	Taipei		Taiwan	100
171	Mackay Memorial Hospital PHASE 2	Taipei		Taiwan
172	The Royal Marsden NHS Foundation Trust PHASE 2	London		United Kingdom	SW3 6JJ
173	Imperial College London - Hammersmith Hospital PHASE 2	London		United Kingdom	W12 0HS
174	Sarah Cannon Research Institute PHASE 2	London		United Kingdom	W1G 6AD
175	The Christie NHS Foundation Trust PHASE 2	Manchester		United Kingdom	M20 4BX