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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03319628




Registration number
NCT03319628
Ethics application status
Date submitted
17/10/2017
Date registered
24/10/2017

Titles & IDs
Public title
First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b
Scientific title
A Phase 1b/2, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients With Solid Tumors Likely to Express NaPi2b
Secondary ID [1] 0 0
XMT-1536-1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Platinum Resistant Ovarian Cancer 0 0
Non Small Cell Lung Cancer Metastatic 0 0
Metastatic Colorectal Cancer 0 0
Growth Hormone Deficiency, Pediatric 0 0
Endocrine System Diseases 0 0
Hormone Deficiency 0 0
Pituitary Diseases 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Infection 0 0 0 0
Other infectious diseases
Cancer 0 0 0 0
Lung - Small cell
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - upifitamab rilsodotin
Treatment: Drugs - TransCon hGH

Experimental: Dose Escalation - XMT-1536 (upifitamab rilsodotin) treatment is administered in groups of patients who will receive doses that increase over time.

This cohort is closed to enrollment.

Experimental: Dose Expansion - Ovarian Cancer - Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose.

This cohort is closed to enrollment.

Experimental: Dose Expansion - NSCLC adenocarcinoma - Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, new groups of patients will receive XMT-1536 (upifitamab rilsodotin) at this fixed-dose.

This cohort is closed to enrollment.

Experimental: Pivotal Cohort (UPLIFT) - Patients with platinum-resistant ovarian cancer will receive XMT-1536 (upifitamab rilsodotin) to further confirm the efficacy.

This cohort is closed to enrollment.

Experimental: QTc Sub-Study - For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536.

This cohort is closed to enrollment.

Experimental: S95005 - Film-coated tablet containing 15 mg of trifluridine and 7.065 mg of tipiracil hydrochloride, or 20 mg of trifluridine and 9.42 mg of tipiracil hydrochloride, taken orally twice a day at the dose of 35 mg/m²/dose. The treatment is given until progression of disease, unacceptable toxicity, investigator decision, patient refusal or until market authorization or reimbursement has been granted by the relevant Authority of the country where that patient is treated or until trifluridine / tipiracil is available by a doctor's prescription or can be accessed from another source or Sponsor decision.

Experimental: TransCon hGH - Once weekly subcutaneous injection of TransCon hGH


Treatment: Drugs: upifitamab rilsodotin
XMT-1536 will be administered once every 28 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study.

For sites participating in the sub-study, patients with platinum -resistant ovarian cancer will have the option to enroll in this sub-study to evaluate potential changes in the QTc interval following administration of XMT-1536

Treatment: Drugs: TransCon hGH
Once weekly subcutaneous injection at a starting dose of 0.24 mg/kg/week

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DES: Maximum tolerated dose or recommended Phase 2 dose
Timepoint [1] 0 0
Up to 36 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met
Primary outcome [2] 0 0
DES and EXP: Safety and Tolerability
Timepoint [2] 0 0
First dose up until 30 days after study termination
Primary outcome [3] 0 0
EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin)
Timepoint [3] 0 0
Every 6 weeks for up to 36 weeks
Primary outcome [4] 0 0
UPLIFT: Investigator-assessed objective response rate (ORR) of XMT-1536 (upifitamab rilsodotin) in the ITT-Higher NaPi2b population
Timepoint [4] 0 0
Every 8 weeks until disease progression or up to 24 months
Primary outcome [5] 0 0
QTc Sub-study: Evaluation of the concentration response analysis of XMT-1536 versus the change in QTcF values
Timepoint [5] 0 0
60 minutes prior to first dose, up to 26 hours after Cycle 3 dose
Primary outcome [6] 0 0
Incidence of Adverse Events [safety and tolerability]
Timepoint [6] 0 0
Through 28 days following last administration of study medication
Primary outcome [7] 0 0
Abnormalities in laboratory assessment
Timepoint [7] 0 0
Through study completion, an average of 12 weeks
Primary outcome [8] 0 0
Abnormalities in performance status (ECOG)
Timepoint [8] 0 0
Through study completion, an average of 12 weeks
Primary outcome [9] 0 0
Abnormalities in vital signs
Timepoint [9] 0 0
Through study completion, an average of 12 weeks
Primary outcome [10] 0 0
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
Timepoint [10] 0 0
26 weeks
Secondary outcome [1] 0 0
DES and EXP: Time of maximum observed concentration of XMT-1536 (upifitamab rilsodotin)
Timepoint [1] 0 0
Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
Secondary outcome [2] 0 0
DES and EXP: Maximum concentration of XMT-1536 (upifitamab rilsodotin)
Timepoint [2] 0 0
Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
Secondary outcome [3] 0 0
DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin)
Timepoint [3] 0 0
Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
Secondary outcome [4] 0 0
DES: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin)
Timepoint [4] 0 0
Every 6 weeks for up to 36 weeks
Secondary outcome [5] 0 0
DES and EXP: Anti-drug antibody and neutralizing antibody
Timepoint [5] 0 0
Every 6 weeks for up to 36 weeks
Secondary outcome [6] 0 0
UPLIFT: Confirmed Investigator-assessed objective response rate of XMT-1536 (upifitamab rilsodotin) regardless of NaPi2b expression
Timepoint [6] 0 0
Every 8 weeks until disease progression or up to 24 months
Secondary outcome [7] 0 0
UPLIFT: Confirmed objective response rate by independent radiology review (IRR) for patients with high NaPi2b and overall
Timepoint [7] 0 0
Every 8 weeks until disease progression or up to 24 months
Secondary outcome [8] 0 0
UPLIFT: Duration of objective response (DOR)
Timepoint [8] 0 0
4 weeks after first response and every 8 weeks until disease progression or up to 24 months
Secondary outcome [9] 0 0
UPLIFT: Incidence and severity of adverse events
Timepoint [9] 0 0
First dose up until 60 days after study termination
Secondary outcome [10] 0 0
QTc Sub-Study: Evaluation of the effect of XMT-1536 on QTcF in patients with platinum-resistant HGSOC by timepoint analysis
Timepoint [10] 0 0
60 minutes prior to first dose, up to 26 hours after Cycle 3 dose
Secondary outcome [11] 0 0
QTc Sub-Study: Evaluation of the effect of XMT-1536 on the PR-interval (PR), QRS duration (QRS), Heart Rate (HR), and ECG morphology
Timepoint [11] 0 0
60 minutes prior to first dose, up to 26 hours after Cycle 3 dose
Secondary outcome [12] 0 0
Progression free survival (PFS)
Timepoint [12] 0 0
Through study completion, an average of 12 weeks
Secondary outcome [13] 0 0
Quality of life using the questionnaire EQ-5D
Timepoint [13] 0 0
Through study completion, an average of 12 weeks
Secondary outcome [14] 0 0
Quality of life using the questionnaire EORTC QLQ-C30
Timepoint [14] 0 0
Through study completion, an average of 12 weeks
Secondary outcome [15] 0 0
Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment
Timepoint [15] 0 0
26 weeks
Secondary outcome [16] 0 0
Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment
Timepoint [16] 0 0
26 weeks
Secondary outcome [17] 0 0
Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment
Timepoint [17] 0 0
Baseline and 26 weeks
Secondary outcome [18] 0 0
Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation
Timepoint [18] 0 0
26 weeks

Eligibility
Key inclusion criteria
General Inclusion Criteria (for Dose Escalation, Expansion, and UPLIFT):

* ECOG performance status 0 or 1
* Measurable disease as per RECIST, version 1.1
* Resolution of all acute toxic effects of prior therapy or surgical procedures to =Grade 1 (except alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency on =10 mg daily prednisone [or equivalent], chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy).
* Cardiac left ventricular ejection fraction (LVEF) =50% or = the institution's lower limit of normal by either Echo or MUGA scan
* Adequate organ function as defined by the following criteria:

1. Absolute neutrophil count (ANC) =1500 cells/mm3
2. Platelet count =100,000/mm3
3. Hemoglobin =9 g/dL
4. In patients not on anticoagulation therapy: INR, activated partial thromboplastin time (aPTT), and prothrombin time (PT) all within 1.2 times the institution's upper limit of normal (ULN). Patients on anticoagulation therapy are allowed if their relevant laboratory values are within the therapeutic window.
5. Estimated glomerular filtration rate (GFR) =45 mL/min
6. Total bilirubin =ULN
7. g. Patients with asymptomatic elevations in unconjugated bilirubin due to Gilbert syndrome or stable chronic hemolytic anemia (e.g., hereditary spherocytosis, sickle cell disease, thalassemia intermedia) may be eligible after discussion with the Sponsor Medical Monitor.
* Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) =1.5 times the institutional ULN.
* Albumin =3.0 g/dL
* Able to provide informed consent.

General
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria (for Dose Escalation, Expansion, and UPLIFT) :

* Major surgery within 28 days of starting study treatment, systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment, or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity.
* Patients with untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
* Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
* Prior history of liver disease such as liver cirrhosis, hepatic fibrosis
* Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
* Current use of either constant or intermittent supplementary oxygen therapy.
* History of suspected pneumonitis or interstitial lung disease.
* Pregnant or nursing women.
* History of other malignancy within the last 2 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
* Active corneal disease, or history of corneal disease within 12 months prior to enrollment
* Use of strong CYP450 3A inhibitors or inducers that cannot be discontinued while receiving study treatment
* Oxygen saturation on room air <93%

Ovarian Cancer Inclusion Criteria for UPLIFT:

* Histological diagnosis of high grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer, that is metastatic or recurrent.
* Platinum-resistant disease

1. Patients who have only had 1 line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response [complete response/remission (CR) or partial response/remission (PR)], and then progressed between 3 months and = 6 months after the date of the last dose of platinum
2. Patients who have received 2 to 4 lines of prior therapy must have received at least 4 cycles of platinum and then progressed within 6 months after the date of the last dose of platinum
* One to 4 prior lines of systemic therapy for ovarian cancer

a. Prior treatment with bevacizumab is required for patients with 1 to 2 prior lines of therapy
* Patients must be willing to provide an archival tumor tissue block or slides or if not available, undergo procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure

Ovarian Cancer Exclusion Criteria for UPLIFT:

* Low-grade, clear cell, endometrioid, mucinous, carcinosarcoma, germ-cell, mixed histology, or stromal tumors
* Prior treatment with mirvetuximab soravtansine or another ADC containing an antitubulin payload
* Primary platinum-resistant disease, defined by a lack of response or by progression within 3 months after completing front-line, platinum-containing therapy.
* Participation in DES or EXP segments of this study

Ovarian Cancer Inclusion Criteria for QTc sub-study:

Note: patients must meet all UPLIFT cohort inclusion criteria in order to participate in the QTc sub-study

• Study patient has agreed to remain in the clinic for the additional QTc related study activities on the Day 1 of Cycle 1 and Cycle 3.

Ovarian Cancer Exclusion Criteria for QTc sub-study:

* Use of strong CYP450 3A inducers.
* Uncontrolled cardiac arrhythmias, for example, atrial fibrillation with a ventricular response at rest > 100 beats per minute. left bundle branch block (LBBB)
* Known abnormality of any cardiac valve (either stenosis or regurgitation) that is greater than moderate in severity.
* Subjects not in sinus rhythm at screening with HR >45- <100
* Any ECG abnormality that can interfere with the measurement of the QT interval

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [2] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [4] 0 0
Chris O'Brien Lifehouse Oncology - Camperdown
Recruitment hospital [5] 0 0
St Vincent's Hospital The Kinghorn Cancer Centre - Darlinghurst
Recruitment hospital [6] 0 0
St Vincent's Hospital (Melbourne) Cancer Centre - Fitzroy
Recruitment hospital [7] 0 0
The Canberra Hospital Cancer,Ambulatory & Community Health Service (CACHS) Bldg 19 - Garran
Recruitment hospital [8] 0 0
Royal Brisbane & Women's Hospital Clinical Research Unit - Herston
Recruitment hospital [9] 0 0
Cabrini Hospital Cabrini Haematology and Oncology Centre - Malvern
Recruitment hospital [10] 0 0
Perth Oncology - Mount Hospital - Perth
Recruitment hospital [11] 0 0
The Queen Elizabeth Hospital Haematology and Oncology Unit - Woodville
Recruitment hospital [12] 0 0
Monash Children's Hospital - Clayton
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
NSW 2050 - Camperdown
Recruitment postcode(s) [5] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment postcode(s) [7] 0 0
2605 - Garran
Recruitment postcode(s) [8] 0 0
3144 - Malvern
Recruitment postcode(s) [9] 0 0
6000 - Perth
Recruitment postcode(s) [10] 0 0
SA 5011 - Woodville
Recruitment postcode(s) [11] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
North Carolina
Country [2] 0 0
United States of America
State/province [2] 0 0
Oklahoma
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Virginia
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United States of America
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Washington
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Argentina
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Buenos Aires
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Argentina
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Buenos Aries
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Austria
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Wels
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Belgium
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Oost-Vlaanderen
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Belgium
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Vlaams-Brabant
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Canada
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Alberta
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Canada
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Ontario
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Chile
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Coquimbo
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Czechia
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Ostrava
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France
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Lyon
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France
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Paris
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Germany
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Baden-Wurttemberg
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Germany
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Bayern
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Germany
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Nordrhein-Westfalen
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Germany
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Schleswig-Holstein
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Germany
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Berlin
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Germany
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Hamburg
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Greece
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Thessaly
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Hungary
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Ulloi
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Haifa
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Israel
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Jerusalem
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Israel
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Ramat Gan
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Israel
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Tel Aviv
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Italy
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MB
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Italy
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Modena
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Italy
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Palermo
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Gyeonggi-do
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Seoul
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Busan
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Ciudad de Mexico
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Metepec
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Nijmegen
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Canterbury
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New Zealand
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Otago
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Katowice
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Zürich
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Ankara
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Fatih
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Istanbul
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Izmir
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United Kingdom
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Devon
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Hampshire
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Nottinghamshire
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Birmingham
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Hull
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London
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Newcastle Upon Tyne
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United Kingdom
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Newcastle
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Poland
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Otwock
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Spain
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Cataluña
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Switzerland
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Lausanne
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Switzerland
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Sankt Gallen
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Taiwan
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Kaohsiung
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Taiwan
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Taipei
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Taiwan
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Taoyuan
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United Kingdom
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Manchester
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Belgium
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Bruxelles
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Belgium
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Edegem
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Belgium
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Gent
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Belgium
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Leuven
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United States of America
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Alabama
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Brazil
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Porto Alegre
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California
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Brazil
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Rio De Janeiro
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Brazil
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Salvador
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United States of America
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Colorado
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Brazil
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São Paulo
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United States of America
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Florida
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Bulgaria
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Plovdiv
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Iowa
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Bulgaria
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Sofia
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United States of America
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Minnesota
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United States of America
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Mississippi
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Bulgaria
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Varna
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United States of America
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New Hampshire
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Croatia
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Rijeka
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United States of America
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New York
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Croatia
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Zagreb
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France
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Arras
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Ohio
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France
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Avignon
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France
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Caen
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United States of America
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Oregon
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France
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Chambray Les Tours
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France
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Dijon
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France
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Grenoble Cedex 9
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France
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La Roche Sur Yon
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France
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Levallois Perret
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France
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Marseille
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New Zealand
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Auckland
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France
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Montbeliard
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Montpellier
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France
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Nice
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France
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Pessac
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France
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Poitiers
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France
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Reims
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Rennes
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Saint Etienne
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France
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TOULOUSE cedex 9
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Ireland
State/province [119] 0 0
Cork
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Ireland
State/province [120] 0 0
Dublin
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Italy
State/province [121] 0 0
Bari
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Italy
State/province [122] 0 0
Brescia
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Italy
State/province [123] 0 0
Catania
Country [124] 0 0
Italy
State/province [124] 0 0
Firenze
Country [125] 0 0
Italy
State/province [125] 0 0
Meldola
Country [126] 0 0
Italy
State/province [126] 0 0
Milano
Country [127] 0 0
Italy
State/province [127] 0 0
Napoli
Country [128] 0 0
Italy
State/province [128] 0 0
Padova
Country [129] 0 0
Italy
State/province [129] 0 0
Pescara
Country [130] 0 0
Italy
State/province [130] 0 0
Pisa
Country [131] 0 0
Italy
State/province [131] 0 0
Reggio Emilia
Country [132] 0 0
Italy
State/province [132] 0 0
Rimini
Country [133] 0 0
Italy
State/province [133] 0 0
Roma
Country [134] 0 0
Italy
State/province [134] 0 0
Rozzano (mi)
Country [135] 0 0
Italy
State/province [135] 0 0
San Giovanni Rotondo
Country [136] 0 0
Italy
State/province [136] 0 0
Torino
Country [137] 0 0
Panama
State/province [137] 0 0
Panamá
Country [138] 0 0
Poland
State/province [138] 0 0
Bialystok
Country [139] 0 0
Poland
State/province [139] 0 0
Gdansk
Country [140] 0 0
Poland
State/province [140] 0 0
Opole
Country [141] 0 0
Poland
State/province [141] 0 0
Poznan
Country [142] 0 0
Poland
State/province [142] 0 0
Warszawa
Country [143] 0 0
Portugal
State/province [143] 0 0
Almada
Country [144] 0 0
Portugal
State/province [144] 0 0
Coimbra
Country [145] 0 0
Portugal
State/province [145] 0 0
Lisboa
Country [146] 0 0
Portugal
State/province [146] 0 0
Porto
Country [147] 0 0
Romania
State/province [147] 0 0
Bucuresti
Country [148] 0 0
Romania
State/province [148] 0 0
Cluj-napoca
Country [149] 0 0
Romania
State/province [149] 0 0
Iasi
Country [150] 0 0
Slovakia
State/province [150] 0 0
Bratislava
Country [151] 0 0
Slovakia
State/province [151] 0 0
Kosice
Country [152] 0 0
Slovenia
State/province [152] 0 0
Ljubljana
Country [153] 0 0
Turkey
State/province [153] 0 0
Bursa
Country [154] 0 0
Turkey
State/province [154] 0 0
Edirne
Country [155] 0 0
Turkey
State/province [155] 0 0
Kayseri
Country [156] 0 0
Ukraine
State/province [156] 0 0
Kharkiv
Country [157] 0 0
Ukraine
State/province [157] 0 0
Kiev
Country [158] 0 0
Ukraine
State/province [158] 0 0
Kyiv
Country [159] 0 0
Ukraine
State/province [159] 0 0
Odesa

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Mersana Therapeutics
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ADIR, a Servier Group company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Robert Burger, MD
Address 0 0
Mersana Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jamie Barrett
Address 0 0
Country 0 0
Phone 0 0
617-715-8214
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.