A Study of Dato-DXd Versus Investigator's Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02)

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05374512

Collaborator

Daiichi Sankyo, Inc. (Industry)

600

Enrollment

238

Locations

Arms

42.6

Anticipated Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase III, randomised, open-label, 2 arm, multicentre, international study assessing the efficacy and safety of Dato-DXd compared with ICC in participants with locally recurrent inoperable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Dato-DXd Drug: Paclitaxel Drug: Nab-paclitaxel Drug: Carboplatin Drug: Capecitabine Drug: Eribulin mesylate	Phase 3

Detailed Description

The primary objectives of the study are to demonstrate superiority of Dato-DXd relative to ICC by assessment of PFS in participants with locally recurrent inoperable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy, per BICR and to demonstrate superiority of Dato-DXd relative to ICC by assessment of OS in participants with locally recurrent inoperable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

600 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants will be randomised in a 1:1 ratio to one of two intervention groups.Participants will be randomised in a 1:1 ratio to one of two intervention groups.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator's Choice of Chemotherapy in Patients Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer (TROPION Breast02)

Actual Study Start Date :

May 16, 2022

Anticipated Primary Completion Date :

Dec 3, 2025

Anticipated Study Completion Date :

Dec 3, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dato-DXd Arm 1: Dato-DXd	Drug: Dato-DXd Experimental drug. Provided in 100mg vials. IV infusion. Other Names: Datopotamab deruxtecan (Dato-DXd, DS-1062a)
Active Comparator: Investigator's Choice of Chemotherapy (ICC) Arm 2: If no prior taxane, or prior taxane in the (neo)adjuvant setting and DFI > 12 months, paclitaxel or nab-paclitaxel If prior taxane and DFI ≤ 12 months: capecitabine, carboplatin, or eribulin.	Drug: Paclitaxel IV Infusion. Active comparator Drug: Nab-paclitaxel IV infusion. Active comparator Drug: Carboplatin IV infusion. Active comparator Drug: Capecitabine Tablet. Oral route of administration. Active comparator Drug: Eribulin mesylate IV infusion. Active comparator

Arm

Intervention/Treatment

Experimental: Dato-DXd

Arm 1: Dato-DXd

Drug: Dato-DXd

Experimental drug. Provided in 100mg vials. IV infusion.

Other Names:

Datopotamab deruxtecan (Dato-DXd, DS-1062a)

Active Comparator: Investigator's Choice of Chemotherapy (ICC)

Arm 2: If no prior taxane, or prior taxane in the (neo)adjuvant setting and DFI > 12 months, paclitaxel or nab-paclitaxel If prior taxane and DFI ≤ 12 months: capecitabine, carboplatin, or eribulin.

Drug: Paclitaxel

IV Infusion. Active comparator

Drug: Nab-paclitaxel

IV infusion. Active comparator

Drug: Carboplatin

IV infusion. Active comparator

Drug: Capecitabine

Tablet. Oral route of administration. Active comparator

Drug: Eribulin mesylate

IV infusion. Active comparator

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [From randomization until progression as assessed by BICR or death due to any cause (anticipated to be up to 26 months)]
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression. However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest evaluable assessment prior to the 2 missed visits. The measure of interest is the hazard ratio [HR] of PFS.
Overall Survival (OS) [From randomisation until the date of death due to any cause (approximately 42 months)]
OS is defined as the time from randomisation until the date of death due to any cause. The analysis will include all randomised participants, by treatment group as randomised. The measure of interest is the hazard ratio [HR] of OS.

Secondary Outcome Measures

Objective Response Rate (ORR) [From randomisation up until progression (anticipated to be up to 26 months)]
ORR is defined as the proportion of participants who have a confirmed CR or PR, as determined by BICR/investigator assessment, per RECIST 1.1. The analysis will include all randomised participants, by treatment group as randomised. Data obtained from randomisation up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR, regardless of whether the participant withdraws from therapy. Participants who go off treatment without a response or progression, receive a subsequent anti-cancer therapy, and then respond will not be included as responders in the ORR. The measure of interest is the odds ratio of the ORR.
Duration of Response (DoR) [From the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause (anticipated to be up to 26 months)]
DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR/investigator assessment or death due to any cause. The analysis will include all randomised participants as randomised who have a confirmed response, regardless of whether the participant withdraws from therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression. The measure of interest is the median of DoR,
Progression-Free Survival (PFS) by Investigator assessment [From randomisation until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause (anticipated to be up to 26 months)]
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by the investigator, or death due to any cause. The analysis will include all randomised participants, as randomised, regardless of whether the participant withdraws from randomised therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST 1.1 progression. The measure of interest is the hazard ratio [HR] of PFS.
Time to deterioration (TTD) in pain in participants treated with Dato DXd compared with ICC [From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression)]
TTD in pain as measured by the pain scale from EORTC IL146. TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analysis will include all randomised participants. The measure of interest is the hazard ratio [HR] of TTD in pain.
Time to deterioration (TTD) in physical functioning in participants treated with Dato DXd compared with ICC [From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression)]
TTD in physical functioning as measured by the physical functioning scale from EORTC IL146. TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analysis will include all randomised participants. The measure of interest is the hazard ratio [HR] of TTD in physical functioning.
Time to deterioration (TTD) in breast and arm symptoms in participants treated with Dato DXd compared to ICC [From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression)]
TTD in breast symptoms as measured by the breast symptoms scale from EORTC IL116 TTD in arm symptoms as measured by the arm symptoms scale from EORTC IL116 TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analysis will include all randomised participants. The measure of interest is the hazard ratio [HR] of TTD in breast symptoms/arm symptoms.
Time to deterioration (TTD) in GHS/QoL in participants treated with Dato DXd compared with ICC [From the date of randomisation to the date of deterioration (from randomization to 18 weeks post-progression)]
TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC IL146. TTD is defined as time from the date of randomisation to the date of deterioration. Deterioration is defined as change from baseline that reaches a clinically meaningful deterioration threshold. The analysis will include all randomised participants. The measure of interest is the hazard ratio [HR] of TTD in GHS/QoL.
Time to First Subsequent Therapy (TFST) [From randomisation until the start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause (anticipated to be up to 26 months)]
TFST is defined as the time from randomisation until the start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause. The analysis will include all randomised participants as randomised, regardless of progression status. The measure of interest is the hazard ratio [HR] of TFST.
Time to Second Subsequent Therapy (TSST) [From randomisation until the start date of the second subsequent anti cancer therapy after discontinuation of first subsequent treatment, or death due to any cause (anticipated to be up to 26 months)]
TSST is defined as the time from randomisation until the start date of the second subsequent anti cancer therapy after discontinuation of first subsequent treatment, or death due to any cause. The analysis will include all randomised participants as randomised, regardless of progression status on study treatment or first subsequent treatment. The measure of interest is the hazard ratio [HR] of TSST.
Progression Free Survival 2 (PFS2) [From randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death (anticipated to be up to 26 months)]
PFS2 will be defined as the time from randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice. The analysis will include all randomised participants as randomised regardless of whether the participant withdraws from subsequent therapy and regardless of missed visits. The measure of interest is the hazard ratio [HR] of PFS2.
Pharmacokinetics of Dato-DXd [From first dose to end of treatment (anticipated to be up to 26 months)]
Concentration of Dato DXd, total anti-TROP2 antibody, and MAAA-1181a in plasma.
Immunogenicity of Dato-DXd [From first dose to end of treatment safety follow-up (anticipated to be up to 26 months)]
Presence of ADAs for Dato-DXd (confirmatory results: positive or negative, titres).
Safety of Dato-DXd [From first dose to end of treatment safety follow-up (anticipated to be up to 26 months)]
Safety will be evaluated in terms of AEs (graded by CTCAE version 5.0)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age

Participant must be ≥ 18 years (≥ 20 years in Japan) at the time of screening. Type of Participant and Disease Characteristics
Histologically or cytologically documented locally recurrent inoperable or metastatic

TNBC. TNBC is defined as:

Negative for ER with < 1% of tumour cells positive for ER on IHC.
Negative for progesterone receptor with < 1% of tumour cells positive for progesterone receptor on IHC.
Negative for HER2 with 0 or 1+ intensity on IHC or 2+ intensity on IHC and negative by in situ hybridisation per the ASCO-CAP HER2 guideline

No prior chemotherapy or targeted systemic therapy for metastatic or locally recurrent inoperable breast cancer.
Not a candidate for PD-1/PD-L1 inhibitor therapy, defined as:

Participants whose tumours are PD-L1-negative, or
Participants whose tumours are PD-L1-positive and have:

relapsed after prior PD-1/PD-L1 inhibitor therapy for early-stage breast cancer,
comorbidities precluding PD-1/PD-L1 inhibitor therapy, or
no regulatory access to pembrolizumab [participant's country does not have regulatory approval at the time of screening]).
At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI), and is suitable for accurate repeated measurements.
ECOG PS 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
Eligible for one of the chemotherapy options listed as ICC (paclitaxel, nab-paclitaxel, capecitabine, carboplatin, or eribulin), per investigator assessment.
Has had an adequate treatment washout period before Cycle 1 Day 1, defined as:

Major surgery: ≥ 3 weeks.
Radiation therapy including palliative radiation to chest: ≥ 4 weeks (palliative radiation therapy to other areas ≥ 2 weeks).
Corticosteroid therapy for central nervous system metastatic disease: > 3 days.
Anti cancer therapy including hormonal therapy: ≥ 3 weeks (for small molecule targeted agents: ≥ 2 weeks or 5 half-lives, whichever is longer).
Antibody-based anti cancer therapy: ≥ 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (eg, denosumab for the treatment of bone metastases).
Chloroquine/hydroxychloroquine: > 14 days.

Written confirmation of tumour sample needs to be available prior to enrolment and tumour samples should be available prior to randomisation. All participants must have a FFPE metastatic (excluding bone) or locally recurrent inoperable tumour sample (block preferred, or a minimum of 20 freshly cut slides) available, collected ≤ 3 months prior to screening. If neither an adequate FFPE block nor the minimum of 20 slides are available from the most recent biopsy, or if a biopsy is not feasible for safety reasons, and this is clearly documented, an archival tumour specimen obtained before the diagnosis of locally recurrent inoperable or metastatic breast cancer may be submitted, pending approval by the Global Study Team.
Participants with a history of previously treated neoplastic spinal cord compression or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants may be included in the study, if they have recovered from acute toxic effects of radiotherapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and study enrolment. A minimum of 3 days must have elapsed between the end of corticosteroid therapy for central nervous system metastatic disease and study enrolment.
Adequate organ and bone marrow function within 7 days before day of first dosing as follows:

Haemoglobin ≥ 9.0 g/dL (red blood cell/plasma transfusion is not allowed within 1 week prior to screening assessment).
Absolute neutrophil count ≥ 1.5 × 10^9/L (granulocyte colony stimulating factor administration is not allowed within 1 week prior to screening assessment).
Platelet count ≥ 100 × 10^9/L (platelet transfusion is not allowed within 1 week prior to screening assessment).
Total bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) if no liver metastases or < 3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN for AST/ALT (< 5 × ULN in participants with liver metastases).
Calculated CrCL ≥ 30 mL/minute as determined by Cockcroft Gault
International normalised ratio (INR) or prothrombin time, and either partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT): ≤ 1.5 × ULN.

Minimum life expectancy of 12 weeks.

Sex

Male or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Reproduction

Negative pregnancy test (serum) for women of childbearing potential.
Female participants must be at least 1 year post-menopausal, surgically sterile, or using at least 1 highly effective form of birth control (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.) Women of childbearing potential who are sexually active with a non sterilised male partner must agree to use at least 1 highly effective method of birth control. They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and continue for at least 7 months after the last dose. Female participants must refrain from egg cell donation and breastfeeding while on study and for at least 7 months after the last dose of study drug. Any non sterilised male partner of a woman of childbearing potential must use a male condom plus spermicide (condom alone in countries where spermicides are not approved) throughout this period.
Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or use an acceptable method of contraception from the time of screening throughout the total duration of the study and the drug washout period (at least 4 months after the last dose of study intervention) to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. Not engaging in heterosexual activity (sexual abstinence) for the duration of the study and drug washout period is an acceptable practice, if this is the preferred usual lifestyle of the participant. Periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

Informed Consent

Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of sample for optional genetic research that supports Genomic Initiative.

Exclusion Criteria:

Medical Conditions

As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, uncontrolled hypertension, history of allogeneic organ transplant, and active bleeding diseases, ongoing or active infection, or significant cardiac or psychological conditions) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence (per investigator assessment). Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that have undergone potentially curative therapy, adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumours curatively treated.
Persistent toxicities caused by previous anti cancer therapy, excluding alopecia, not yet improved to Grade ≤ 1 or baseline. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss) after consultation with the sponsor study clinical lead or designee. Note: per the discretion of the investigator after consultation with the sponsor study clinical lead or designee, participants may be enrolled with some chronic, stable Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to first dosing and managed with SoC treatment) which the investigator deems related to previous anti cancer therapy.
Uncontrolled infection requiring IV antibiotics, antivirals or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections (participants with localised fungal infections of skin or nails are eligible).
Known active or uncontrolled hepatitis B or C virus infection; or is positive for hepatitis B or C virus, based on the evaluation of tests for hepatitis B (hepatitis B virus surface antigen, anti-hepatitis B virus surface antibody, and anti hepatitis B virus core antibody, or hepatitis B virus DNA) or hepatitis C (hepatitis C antibody or hepatitis C virus ribonucleic acid [RNA]) infection at screening. Participants who have received hepatitis B vaccination with only anti-hepatitis B virus surface antibody positivity and no clinical signs of hepatitis, and participants who have been curatively treated for hepatitis C infection (as demonstrated clinically and by viral serologies) are eligible.
Known human immunodeficiency virus (HIV) infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, cluster of differentiation (CD)4+ count > 250 cells/mm3, no history of an acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications.
Uncontrolled or significant cardiac disease including:

Myocardial infarction or uncontrolled/unstable angina within 6 months prior to Cycle 1 Day 1
Congestive heart failure (New York Heart Association Class II to IV), or
Uncontrolled or significant cardiac arrhythmia, or
Uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg).

Investigator judgment of any one of the following:

Mean resting corrected QT interval corrected by Fridericia's formula (QTcF) > 470 ms regardless of gender, obtained from triplicate 12-lead electrocardiograms (ECGs) performed at screening.
History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and/or cause Torsades de Pointes.
Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.

Uncontrolled hypercalcaemia: > 1.5 mmol/L (> 6 mg/dL) ionised calcium, or serum calcium (uncorrected for albumin) > 3 mmol/L (> 12 mg/dL), or corrected serum calcium

ULN, or clinically significant (symptomatic) hypercalcaemia.

History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
Clinically severe pulmonary function compromise resulting from intercurrent clinically significant pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of first dosing, severe asthma, severe chronic obstructive pulmonary disease (COPD), restrictive lung disease, pleural effusion, etc.) or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.) where there is documented or suspected pulmonary involvement at the time of screening.
Leptomeningeal carcinomatosis.
Clinically significant corneal disease.
Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).

Prior/Concomitant Therapy

Prior exposure to:

Any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I
TROP2-targeted therapy
Prior treatment with same ICC agent
Chloroquine/hydroxychloroquine without an adequate treatment washout period of > 14 days prior to randomisation.

Any concurrent anti cancer treatment.
Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy [HRT], except topical).
Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 3 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.
Receipt of live, attenuated vaccine within 30 days prior to the first dose of study treatment.
Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications except for managing AEs (inhaled steroids or intra articular steroid injections are permitted in this study).

Prior/Concurrent Clinical Study Experience

Previous treatment in the present study.
Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to first dose of study intervention, randomisation into a prior T-DXd or Dato DXd study regardless of treatment assignment, or concurrent enrolment in another clinical study, unless it is an observational (non interventional) clinical study or during the follow-up period of an interventional study.
Participants with a known severe hypersensitivity to Dato DXd or any of the excipients of the product, including but not limited to polysorbate 80.
Known history of severe hypersensitivity reactions to other monoclonal antibodies.

Other Exclusions

Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
Currently pregnant (confirmed with positive pregnancy test) or breast feeding or planning to become pregnant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Duarte	California	United States	91010
2	Research Site	Los Angeles	California	United States	90017
3	Research Site	San Francisco	California	United States	94143
4	Research Site	Santa Rosa	California	United States	95405
5	Research Site	Stanford	California	United States	94305
6	Research Site	Grand Junction	Colorado	United States	81501
7	Research Site	Longmont	Colorado	United States	80501
8	Research Site	New Haven	Connecticut	United States	06510
9	Research Site	Washington	District of Columbia	United States	20010
10	Research Site	Atlanta	Georgia	United States	30322
11	Research Site	Lexington	Kentucky	United States	40503
12	Research Site	Louisville	Kentucky	United States	40207
13	Research Site	Baton Rouge	Louisiana	United States	70808
14	Research Site	Shreveport	Louisiana	United States	71105
15	Research Site	Baltimore	Maryland	United States	21201
16	Research Site	Boston	Massachusetts	United States	02111
17	Research Site	Detroit	Michigan	United States	48201
18	Research Site	Florham Park	New Jersey	United States	07932
19	Research Site	Hackensack	New Jersey	United States	07601
20	Research Site	Ridgewood	New Jersey	United States	07450
21	Research Site	New York	New York	United States	10065
22	Research Site	Charlotte	North Carolina	United States	28204
23	Research Site	Columbus	Ohio	United States	43210
24	Research Site	Providence	Rhode Island	United States	02903
25	Research Site	Sioux Falls	South Dakota	United States	57105
26	Research Site	Nashville	Tennessee	United States	37203
27	Research Site	Austin	Texas	United States	78731
28	Research Site	Fort Worth	Texas	United States	76104
29	Research Site	Houston	Texas	United States	77030
30	Research Site	Kingwood	Texas	United States	77339
31	Research Site	San Antonio	Texas	United States	78240
32	Research Site	Charlottesville	Virginia	United States	22908
33	Research Site	Midlothian	Virginia	United States	23114
34	Research Site	Norfolk	Virginia	United States	23502
35	Research Site	Spokane Valley	Washington	United States	99216
36	Research Site	Morgantown	West Virginia	United States	26506
37	Research Site	Madison	Wisconsin	United States	53792
38	Research Site	Caba		Argentina	1414
39	Research Site	Anderlecht		Belgium	1070
40	Research Site	Brasschaat		Belgium	2930
41	Research Site	Gent		Belgium	9000
42	Research Site	Liège		Belgium	4000
43	Research Site	Namur		Belgium	5000
44	Research Site	Sint-Niklaas		Belgium	9100
45	Research Site	Blumenau		Brazil	89010-340
46	Research Site	Brasília		Brazil	70200-730
47	Research Site	Curitiba		Brazil	80440-220
48	Research Site	Florianópolis		Brazil	88034-000
49	Research Site	Goiânia		Brazil	74000-000
50	Research Site	Jaú		Brazil	17210-120
51	Research Site	Porto Alegre		Brazil	90619-900
52	Research Site	Porto Alegre		Brazil	91350-200
53	Research Site	Rio de Janeiro		Brazil	20560-120
54	Research Site	Sao Paulo		Brazil	01246-000
55	Research Site	São Paulo		Brazil	01321-001
56	Research Site	São Paulo		Brazil	01409-001
57	Research Site	Calgary	Alberta	Canada	T2N 4N2
58	Research Site	Barrie	Ontario	Canada	L4M 6M2
59	Research Site	Hamilton	Ontario	Canada	L8V 5C2
60	Research Site	Ottawa	Ontario	Canada	K1H 8L6
61	Research Site	Toronto	Ontario	Canada	M5G 2M9
62	Research Site	Montreal	Quebec	Canada	H3T 1E2
63	Research Site	Montreal	Quebec	Canada	H4A 3J1
64	Research Site	Saskatoon	Saskatchewan	Canada	S7N 4H4
65	Research Site	Quebec		Canada	G1S 4L8
66	Research Site	Beijing		China	100021
67	Research Site	Beijing		China	100039
68	Research Site	Beijing		China	100044
69	Research Site	Bengbu		China	233060
70	Research Site	Changchun		China	130021
71	Research Site	Changsha		China	410008
72	Research Site	Changsha		China	410013
73	Research Site	Chengdu		China	610000
74	Research Site	Chongqing		China	400016
75	Research Site	Guangzhou		China	510060
76	Research Site	Guangzhou		China	510100
77	Research Site	Hangzhou		China	310003
78	Research Site	Hangzhou		China	310009
79	Research Site	Hangzhou		China	310022
80	Research Site	Hefei		China	230031
81	Research Site	Hefei		China	230601
82	Research Site	Jinan		China	250001
83	Research Site	Nanchang		China	330009
84	Research Site	Nanjing		China	210029
85	Research Site	Shandong		China
86	Research Site	Shanghai		China	200025
87	Research Site	Shanghai		China	200032
88	Research Site	Shenzhen		China	518029
89	Research Site	Tianjin		China	300060
90	Research Site	Xian		China	710100
91	Research Site	Zhengzhou		China	450008
92	Research Site	Zhengzhou		China
93	Research Site	Bordeaux		France	33076
94	Research Site	Dijon		France	21079
95	Research Site	Limoges		France	83000
96	Research Site	Lyon		France	69373
97	Research Site	Marseille		France	13273
98	Research Site	Montpellier		France	34298
99	Research Site	Rouen		France	76021
100	Research Site	Saint Cloud		France	92210
101	Research Site	Saint Herblain Cedex		France	44805
102	Research Site	Aschaffenburg		Germany	63739
103	Research Site	Bonn		Germany	53111
104	Research Site	Düsseldorf		Germany	40479
105	Research Site	Frankfurt am Main		Germany	60341
106	Research Site	Georgsmarienhuette		Germany	49124
107	Research Site	Gerlingen		Germany	70839
108	Research Site	Hamburg		Germany	20357
109	Research Site	Hannover		Germany	30625
110	Research Site	Heilbronn		Germany	74078
111	Research Site	Koblenz Am Rhein		Germany	56068
112	Research Site	Langen		Germany	63225
113	Research Site	München		Germany	81377
114	Research Site	Münster		Germany	48149
115	Research Site	Wiesbaden		Germany	65199
116	Research Site	Budapest		Hungary	1062
117	Research Site	Budapest		Hungary	1122
118	Research Site	Győr		Hungary	9024
119	Research Site	Miskolc		Hungary	3526
120	Research Site	Nyíregyháza		Hungary	4400
121	Research Site	Zalaegerszeg		Hungary	8900
122	Research Site	Jaipur		India	302022
123	Research Site	Nagpur		India	440001
124	Research Site	Nashik		India	422009
125	Research Site	New Delhi		India	110085
126	Research Site	Pondicherry		India	605006
127	Research Site	Vadodara		India	391760
128	Research Site	Vizag		India	530040
129	Research Site	Aviano		Italy	33081
130	Research Site	Borgo San Lorenzo		Italy	50032
131	Research Site	Catanzaro		Italy	88100
132	Research Site	Genova		Italy	16132
133	Research Site	Macerata		Italy	62100
134	Research Site	Milano		Italy	20132
135	Research Site	Milan		Italy	20141
136	Research Site	Modena		Italy	41124
137	Research Site	Napoli		Italy	80131
138	Research Site	Napoli		Italy	80131
139	Research Site	Roma		Italy	00137
140	Research Site	Rozzano		Italy	20089
141	Research Site	Chuo-ku		Japan	104-0045
142	Research Site	Fukushima-shi		Japan	960-1295
143	Research Site	Hiroshima-shi		Japan	730-8518
144	Research Site	Isehara-shi		Japan	259-1193
145	Research Site	Kagoshima-shi		Japan	892-0833
146	Research Site	Kitaadachi-gun		Japan	362-0806
147	Research Site	Koto-ku		Japan	135-8550
148	Research Site	Kyoto-shi		Japan	606-8507
149	Research Site	Matsuyama-shi		Japan	791-0280
150	Research Site	Nagoya-shi		Japan	464-8681
151	Research Site	Nagoya-shi		Japan	466-8560
152	Research Site	Nagoya-shi		Japan	467-0001
153	Research Site	Niigata-shi		Japan	951-8566
154	Research Site	Nishinomiya-shi		Japan	663-8501
155	Research Site	Sendai-shi		Japan	980-8574
156	Research Site	Shinagawa-ku		Japan	142-8666
157	Research Site	Shinjuku-ku		Japan	162-8655
158	Research Site	Tsukuba		Japan	305-8577
159	Research Site	Yokohama-shi		Japan	241-8515
160	Research Site	Daegu		Korea, Republic of	41404
161	Research Site	Goyang-si		Korea, Republic of	10408
162	Research Site	Seoul		Korea, Republic of	03080
163	Research Site	Seoul		Korea, Republic of	03722
164	Research Site	Seoul		Korea, Republic of	06273
165	Research Site	Seoul		Korea, Republic of	06351
166	Research Site	Seoul		Korea, Republic of	5505
167	Research Site	CD Mexico		Mexico	04980
168	Research Site	Guadalajara Jalisco		Mexico	44280
169	Research Site	Guadalajara		Mexico	44670
170	Research Site	Mexico City		Mexico	0 3100
171	Research Site	Mexico		Mexico	14080
172	Research Site	Mexico		Mexico	6760
173	Research Site	Bacolod		Philippines	6100
174	Research Site	Cebu City		Philippines	6000
175	Research Site	Cebu		Philippines	6000
176	Research Site	Iloilo City		Philippines	5000
177	Research Site	Quezon City		Philippines	1112
178	Research Site	Bydgoszcz		Poland	85-796
179	Research Site	Skórzewo		Poland	60-185
180	Research Site	Tomaszów Mazowiecki		Poland	97-200
181	Research Site	Warszawa		Poland	02-781
182	Research Site	Wroclaw		Poland	53-413
183	Research Site	Łódź		Poland	93-338
184	Research Site	Bukit Merah		Singapore	169610
185	Research Site	Singapore		Singapore	119074
186	Research Site	Singapore		Singapore	308433
187	Research Site	Singapore		Singapore	329563
188	Research Site	Amanzimtoti		South Africa	4126
189	Research Site	Cape Town		South Africa	7570
190	Research Site	Johannesburg		South Africa	2196
191	Research Site	Pretoria		South Africa	0002
192	Research Site	Pretoria		South Africa	0081
193	Research Site	Soweto		South Africa	2013
194	Research Site	Barcelona		Spain	08028
195	Research Site	Barcelona		Spain	08035
196	Research Site	Granada		Spain	18016
197	Research Site	L'Hospitalet de Llobregat		Spain	08908
198	Research Site	Madrid		Spain	28034
199	Research Site	Madrid		Spain	28046
200	Research Site	Majadahonda		Spain	28222
201	Research Site	Málaga		Spain	29010
202	Research Site	Santiago de Compostela		Spain	15706
203	Research Site	Sevilla		Spain	41013
204	Research Site	Hsinchu		Taiwan	300
205	Research Site	Taichung		Taiwan	40447
206	Research Site	Taichung		Taiwan	40705
207	Research Site	Tainan City		Taiwan	70403
208	Research Site	Tainan		Taiwan	710
209	Research Site	Taipei City		Taiwan	11217
210	Research Site	Taipei		Taiwan	10002
211	Research Site	Taipei		Taiwan	10449
212	Research Site	Taoyuan		Taiwan	00333
213	Research Site	Bangkok		Thailand	10210
214	Research Site	Bangkok		Thailand	10330
215	Research Site	Bangkok		Thailand	10400
216	Research Site	Chiang Mai		Thailand	50200
217	Research Site	Dusit		Thailand	10300
218	Research Site	Hat Yai		Thailand	90110
219	Research Site	Khon Kaen		Thailand	40002
220	Research Site	Ankara		Turkey	06340
221	Research Site	Ankara		Turkey	06520
222	Research Site	Diyarbakir		Turkey	21280
223	Research Site	Istanbul		Turkey	34662
224	Research Site	Izmir		Turkey	35100
225	Research Site	Izmir		Turkey	35575
226	Research Site	Konya		Turkey	42080
227	Research Site	Malatya		Turkey	44280
228	Research Site	Bristol		United Kingdom	BS2 8ED
229	Research Site	Cardiff		United Kingdom	CF14 2TL
230	Research Site	Edinburgh		United Kingdom	EH4 2XU
231	Research Site	Inverness		United Kingdom	IV2 3UJ
232	Research Site	London		United Kingdom	EC1A 7BE
233	Research Site	London		United Kingdom	SE1 9RT
234	Research Site	London		United Kingdom	SW17 0QT
235	Research Site	Northampton		United Kingdom	NN1 5BD
236	Research Site	Nottingham		United Kingdom	NG5 1PB
237	Research Site	Swansea		United Kingdom	SA2 8QA
238	Research Site	Warwick		United Kingdom	CV34 5BW