%22%2F%3E%0A%3Cdefs%3E%0A%3Cpattern%20id%3D%22pattern0%22%20patternContentUnits%3D%22objectBoundingBox%22%20width%3D%221%22%20height%3D%221%22%3E%0A%3Cuse%20xlink%3Ahref%3D%22%23image0_10319_58637%22%20transform%3D%22scale(0.00350877%200.0142857)%22%2F%3E%0A%3C%2Fpattern%3E%0A%3Cimage%20id%3D%22image0_10319_58637%22%20width%3D%22285%22%20height%3D%2270%22%20xlink%3Ahref%3D%22data%3Aimage%2Fpng%3Bbase64%2CiVBORw0KGgoAAAANSUhEUgAAAR0AAABGCAYAAADxVED7AAAAAXNSR0IArs4c6QAAE2xJREFUeF7tXY3xJUUR38nAIwHFBBQTQEhAMAE5E1BMQDABIAG9iwCMgCMCIQGBCCCDsX7r9FZvb%2Fd0z%2B68938cvVVXd3Vvdz56en7T31OWfJICSYGfNQVqrb8FAUopX9%2BDEOUenWQfSYGkwGNRoNb6i2VZ%2FrIsy1%2BXZcG%2F8fy4LMunpZSPbznaBJ1bUjfbTgo8IAVqrQCbjxjYyFG%2BKKU8v9XQE3RuRdlsNynwYBRo0s0ny7J8EBjaB6WUl4H3hl9J0BkmWX6QFPjpUaDW%2BqtlWb5clgV%2FR56vSylvRV4cfSdBZ5Ri%2BX5S4CdGgROAQzN8p5TyavZ0E3RmUzTbSwo8EAUuAA5m8VkpBYbmqU%2BCzlRyZmNJgcehwEXAwURelVLemT2jBJ3ZFM32kgIPQIEJgINZ%2FFhKeTZ7Ogk6syma7SUFnpgCkwCHZvFmKeW7mVNK0JlJzWwrKfDEFJgMOJjN81LKi5nTStCZSc1sKynwhBRocTj%2FGXCLR0b7YSnl08iL0XcSdKKUyveSAg9OgVorAGfNowo8ny3LAgnmcwekpkcnJ%2BgEVidfSQo8OgVqrYg0jrq3N%2Bml1opv8K31%2FLuU8t7M%2BSfozKRmtpUUeAIK1Fr%2F3nKpvN6R0AnA2Ww0tVYACqQd65kemZyg4y1T%2Fp4UeGAKtOTNqM3lLVm%2Bohmev%2B1M8btSypszSZCgM5Oa2VZS4I4UqLX%2BvuVTRXo1vVC11tppYHqsToJOZLnynaTAg1Fg0DXedXvXWiHpmImgpZSpODG1sQdblxxOUuC1pMBMwAGBaq3IPofUpD4JOq8lG%2BWkkgJxCgy4xkOBfbVWGJb%2F1BnB1KjklHTia51vJgWenAIDnqoQ4DRJB1UE4QGzngSdJ1%2F5HEBS4Ako4HiqIK1slf5G6uAEYnUSdJ5gvbPLpMCTUqDd2ICIY%2B1BIfUflLrHuN0BsTnfLMuCb7%2FXwKjWivKl%2F%2BpM8OBqv0KMVK%2BuUC%2B%2FTQrcgQIBwzHKilqApI0QYPQV6uUsy0LABBXrN4ZBeWoFwQSdOzBNdpEUuEIBz7u0LAuC93oBfl73KF0BAMIfSEVwnyNS%2Be327wQdj4L5e1LgdaFA0HCMQlsAHbq%2FCvlU%2BBMtwi7JRZLQF%2B0HRCVPq6mTks7rwp05j9eOAoEUBcx59VLVWpEKgfus8Kw2mBaxDHtNzx3u0Y2kICR%2BEgh533R%2FT9C5RL78OClwGwoEa%2BNsbnGREvFxKQU2mvVp4IXgP7jFz0o%2FaApGaQDPJQBK0LkNz2SrSYFLFAiUqjjE4TDbD8ABbm78vXsmST8cgF6OuOfxYYLOJdbIj5MC8ynguMc3lUoBFEgxZFDeSTvGu6R6XZF%2B0DSpYLiyBvagVK88IuTvSYFHokAnAfNQD0cBE7Lt4F3YdlwDcIvTgd3HzL8aoA9c9wAf80rilHQGqJmvJgVuTYFOoB5ABK7rriQhbEFflFLej4y52X3wKmxBVwzP1B0kLkhbB%2FBJ0ImsSL6TFLgTBQwpJwQ4NERRDTAUY1NrJbBZDcVN6gH4XFW9kMH%2BZy5xJejciZmym6SARwGjKNcQ4DDgQQlSBPhBvYKadTAq8%2FEoEhZyuVC8HYXe4YqPFnzXpgmp510CngQdjxPy96TAnSjQpA2Z7d01CFtDG1WzOmrderVwA0SAz9ki7RvwJOjciaGym6SARwGjSPqnpZQPvW%2B134Xk1L2%2FqlP6dFcjudl%2Bztp9viylvJugc2Y185ukwI0oYORZfVRKQSb58MMilbverI6bfpV0ZMcNpJCZPmLzQS3mNxJ0hpcxP0gK3JYChpoF2wyMwq4LXAEIKkdq2nc6KRdwf6v3adVagR8Anqi3C6Dzu2HQaciJFHh6IH49v%2B0yjLfedFoQ45vRiMnx3q5%2F0cbbu3%2FobCeo5h9ym57tIL%2BbT4GOGgMDL%2Bw8YfARpTFUN3oHdDy1DBnu%2Fw1SYBx0OgN75lnHg4O6%2FFobI8AG6Iys23DZxsudX2ggmNx3pofp9xadGUR%2Bc44CHfAZUrma%2BgSJB3vi8G2H%2F0yXe5N0%2FrksCyKbI8%2B3pZRfD0k6nbKGpyzskVGOvqMUmU7QmXxZ2uia5PvXKWCAD6QdAIgZ%2Fct7Fh6qHfCMChRMMh%2BJYl5xYhR0rPtxVGPTdVKPt5Cgc6BZSjrjbPSwX3TAB4crinB1H2Ev2oDH8F6pVwqfNCKvUg4GFwadwG2CochHjyhXf%2F%2Bpgs7VeeP7xpDIfaFiTvjvh5FCZ8wx2%2Fg%2FBQzwCdl7BPBAWoKk9AclAHBnz2nSDeKIVMNyZ23OBQcqmxk5IDxK8SGY%2B%2BcKOkb9lYeRQBMsbkOBs%2BBjeMjkILdbIE5KN2hvBzhhSacxNKrN80fWZb1853EjIPz%2B%2BIO4AvyBiNcN4RZ6q7w47G42nTZ%2BADFJGuscImLvVZZUwHbYxdqMjaA9xo%2Fvp5apvDpH%2Bb2gN8YLWrulFbxxNH4HHehQPcWL1I%2FSHn5Cm6Dv5fEakg%2Fo8aIX3%2BMAySpEXJBuVMAZAR15RQUm81wJZBpWsdrEEVoNjxNXCzhvYGEQmXkwmLWNwkOzpZiIBDYUm6YHILaVXWzGcd4v%2BtlAro0PY1vBpAijbFsUhIeTt0zjaaq4NuTq9DYHY2r0j5IG%2FAmtBZsfaKjRfzVWtmpxKvi3zc89GBuNWegC2peADBsEXLghQyjbXNw7KclEtV2Gad1oAfWhZxzFmMH%2F7pgbXcAXPd7GeLF2qMYXdoNbvKFIPq6xmZW2ANASWL1s92xh7a192WNRHP5Qzw48E7LpWOCieLNWMBrYLJ8M6oeH0ztwZ48czm6MSlbvKlJapwC%2F17kBHmJrRqIyzcWI0k1IdrxwE%2F3kqroNDBDYFc2lAe3f105mxd5HhxI2byRqNWqLALiObIKQW7ltVIxzxBPTlSRPbFi0h0A8eXicYQvN5uOCDzvEqLTpCD3oc2hE%2F%2BjNwwUdxZW2eUMa4%2FIq9GaZREU01gCHJAK8DnTFySg39C7r9hag006mrcYsHzuBTucuIpyEdGJZc5hiazHG4LbdGTskShL3QXeN6T6Qp7wGOq08wkiwYzcbutYKUJDxICTVYIlIHZKnchd4nHWEhEwnNQJiJUCrGeDGDQ54F7xB7Vn07QbjjSKQAqhYX%2FRx8HRdVKUwtEMZC228EdCRNhIpKVCINbXv2lAUoMBC4LtDtfn2LgCKM9PGoC1JjqrgE%2FNxoFptE2zyEOeRsr8%2BiqSD6F1zszDQkeEDWExIAgcR2YhvOmzeEwxF5Qvo05AdR5mzyoiGkfKQw6OADhhaU6XwrQXEmIOa3KjUC8Y8VRexYSBVaW0ATq9t8BVozh0oO3oY8S7gN4DfTtVo74K3OZiFD%2B4RflEk9510eUIy49270s3u4PYGbqkfbNNKe0%2FkpJVA1d2AwhWMDYIiQzvbCxvPkCFZmR9tDDRJfeFvMlSuoCJKPHZP6fa%2BvKRejYHw1oPNE7YHKY25dhzlFMbc8J1prFc28m6NO%2BEUaBMb7rBWHSPmbg7KAeUCq3GoHQqVnzG%2BN2kA%2FEvAA4CF5LBKiI1X%2Bc0LrslBMV%2B46nGUTxQNA%2FuVboVY16apwGdUqbB0EwYdJdX%2BsFEUFQvtd9Miaq3IwaAn5PVqY3E9QaMu80492pCYSx4U704gg06nLqY3MoJdRjVO4dAYaq2I%2F%2BEn%2FAYOZ4tPGZLGLsFQWZ%2BQhKjwgXYti7wVM0oLbFD8UQ8%2BdjBAgsGe6RqIlX3mHtxnQYeNDWsJp0vPAdLrBgcKaDpsg%2BqqV8rCWWKqlC68SvTDoBMl8iTQCQFOdExsoaWE914pBVJb%2BDlrx2mnMBgM4jw97inMxm5%2Ba4BOiIaK6gkvzqpuKO2Go6u9bxU%2BuflGtxZZCUkJHcRhphEvtkMLNrKz1QAh3UG9PeVtM0Fn5FTUdHqtBgdjYOiA3EYT8jJEiDwBdG7GfKNj0%2BariOKuusHoLqWVMOgp%2FLBtDG%2BD99ZNaXeTpsWtlWjGLLNg0Era3Xiwm%2FwtJEFFePDMO0L6X7iX9Ex7HYAb9QDypkzb68gYe6AjbTXbCWQssASSXnaqPPHR5FqT9Wqw1OjGPiu%2BjxCZbfohe5Psw%2FCKuHacJjUA5GWA51B1gFqrXGMeXoA1pafLK8q8uOTLvaOST0JzZfSWhna6ghcnPACYPyHV6sy6R76RfDgbdE6GBfChq8bwyNzkOz3QGToJRk4lJ4%2BLLm9fXc%2BjIDQBdNZ7oM8QU9lMFN1Lf8u7hVxPH9tAUDmkV82147Dv5UbDqTVaZ0fG3KySkhWnE6WhOOU56EiQQwzYiEgvA%2F1WSUkzNJdSnkXHe%2FW9pk7hECC%2BwL93HtqZoHMhhQFTXb15o5kBPRqpoKMYKle3oENsCgSj17p6aTD3gyYNEAhFrk4AnaHTn0kRFHH7dlMdIwGDIdC5YsdhoIP14dLI1b2D70lykG2HbUWNfpakw%2F9%2FxngpaHGqJ7E3sLaXwBMAfYo7i0T4TpG8mit82Njb5gTpBtI5ABFrHAri9BbKAh2pBnjtWL93xeFg2DlvO5JPMqTCXBFrT4xf0ikKOlLqDNtxGOhIdfnsmvLvKD9nOugYNsWrYybQkTwy3Y7XVGHQPHL4aPO6DDqGOh6h4S5uqxn7YQuiuQC0cYf5iNS59WuBjlU3JzJg%2Fk7oxGsMBvedzM%2Bx%2BjM33VVJJyrWBi64XxP6lmX5qmXaft9OCx7I6ILOFTsOJ57ilsXY3PwhZ8GxWV%2FdQr0ykoxPFSdnc0BNF%2BQU3Qx0OhHO8vDExgZPUBS4TKe5BDoXAEdV2c%2FkdFm8cwCdE2kFPb48FV3ZRFKKI9BSIUjtOlwidg%2FQ6QDOmsBoJe8pKqVXf1aTTsJ2HAE6UhoJu5%2B9k%2BYWoKOoXdM8Oso6TKFFB3CwDwDw4A8A9SEQ0wvC9dZArLUWOOo1AfDDIehdWwye5PanQ%2BkKryMNdKTHAHrdiGFV3gYYitdw9GIeRclfPbR9a9CxKqxZ%2BSyCGaQtwQQQEYVNzZxWA3o5dB6TeL%2FfEHRMl7c3pgA%2FwShOz5S4GIX30H7I6zMLdE5KOKOhCFCzgBNcdfyklPK3yLrsQGckNsdq3AuZjwxKe8c4RQ6u2TuAjpbv5F7b2k7uUBClUZBr2I4j6ai4vIeN5sbaTLfpNHpJWofjihzQ0VzmQ%2B54gw7S8B0yL7S5quEII%2FvFuKyv14SZZxbpV9lrIeCRoCOjTodPVkMXn8Xcbp7XHUBHnr5hdUc5zSz9WcvAn7EphpNzg8x3K9CR%2FDh0IjvAIzd5eB2DwIvXQuEXRlrLkE3HOKh6JNgSlJkLH141cuXjW5Jkftka4i5%2Bepf38UMp5Q2PZyToDMXmdKQdydyXFpT6iUQ%2B3wF05GnmGoPbSaa5rA90MVycs%2Bh3%2BVAJbrjwCd9oY7nMZa2gUzZCY8xwI3Oj%2FqW2DbU7BByGWhb6lu2NUe8k2ZUi7nsPR%2Bj3z0spf%2FRe3kBHIdppPVfJpzlITCwbt0aqsDXmdE%2B%2BO4COBGZ3g3VOoUgS4rC02TkMwGC8%2FhFeRTmOQ0kRRTWjUhWH8rG3sum0NZcHWOhub0rEtQJMDVPCSNuwCUHyWmlnSCuudNq5zncUdLQof2%2F%2Fz%2Fw9VEsHHXLQ6dbNGRmdoWKtC9D0TizYUO6VYdM5LIwCOp6HaAcinstcibwGaUxbQxu3rMFC5JSgczkex1sn5UBQC1HxdhTayxoyN1GvOhKit6bS0InxIrdql1xrrKVX9At8ixQKUj22ioqKzcyrLogQEbkXiPQh1YxJOlJd9Fhh1u%2FwyIGP3etvqMMVdHogcXZkSmLipo8bl8QD9MAUO5diOwm0FHxVvzdqpCCMG8wC3RS4skVojgYHdoLWaPy8MhzFHhEZsTC8bskmJd0oGI76lTVqtFPxEPDVqf8swfJmoNP4U3r98N9qdKwR8m%2Fd3wSe4LVx%2BDrtNlKjBeYJe5ssErc6Ejp3kIOvSZokPgTgEC%2BAZ2Bj4bzhSkniYLgn6ICPEX%2B2xmmNYgSBjtQHL8ctKJZ0npVsLXZ0%2FIiGVK8y7dxCSm13ayR7ko6h5kXGjcA2bBRew4WXcdBqHUfajbwjQadHf6q0yI2GvI8D2N9SvWInuQY8%2BJk2LM9l4uPtFilzJFG0w0vPSvvHQZIxDtTeGq2SZivFOhQ4KkBH2qgifBF9B2MEaAJokI5kFnyLNEigc4jNQWJcpAHrHaNolWR%2BMBKSIKOh4m7hoIAV%2FzLoNOCxYockSTa3pCJR8uTGu4FOYCNry2rS%2Fh6gM0hzGn8oRqYjTfW2gNm2obZpbW11aZTDcshTF4yEjm5pSrrG35BmTqU7WJ0Vdicxf%2Bd0gR6BvgAVJLvRs6tP3BabClRDFeF3DdE3VHw7jLIsZBvqFNe90RakC34FDewt2wnWqwMkiciM4dsVNe0dGvOurzbfXX%2FNkAvRHOPkAWtRBom8t5XTNOZgpaCQFAF6QbpUT7imAvPiYId17g2ySQfbens3irBSsbwOM76n1BOznK0zDuJFuZ6cF1dVyVMr2nri4Ab%2Fk9TIU2N2bbA8PurrK9w7FVlcdoigH%2FRJe8n7HHwq0zFwEF6SZLxO3cLsXgP5%2B%2BtFARazAXX4psw3g3JsvDDWTT2RedvtIr%2BHpwcDIEofouqARBtSn59sff8H57piU0311KcAAAAASUVORK5CYII%3D%22%2F%3E%0A%3C%2Fdefs%3E%0A%3C%2Fsvg%3E%0A)
Safety and efficacy of MEDI0457 and Durvalumab in participants with Human Papilloma Virus (HPV) associated recurrent/metastatic head and neck cancer
Study identifier:D8860C00005
ClinicalTrials.gov identifier:NCT03162224
EudraCT identifier:N/A
CTIS identifier:N/A
Study Complete
Official Title
A Phase 1b/2a, Multi-Center Open-Label Study to Evaluate the Safety and Efficacy of Combination Treatment with MEDI0457 (INO-3112) and Durvalumab (MEDI4736) in Patients with Recurrent/Metastatic HPV Associated Head and Neck Squamous Cancer
Medical condition
head and neck cancer
Phase
Phase 1/2
Healthy volunteers
No
Study drug
MEDI0457, Durvalumab
Sex
All
Actual Enrollment
35
Study type
Interventional
Age
18 Years - 99 Years
Date
Study Start Date: 26 Jun 2017
Primary Completion Date: 19 Mar 2021
Study Completion Date: 19 Mar 2021
Study design
Allocation: Non-randomized
Endpoint Classification: Safety
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Verification:
Verified 01 Aug 2022 by MedImmune, LLC
Sponsors
MedImmune, LLC
Collaborators
-
Inclusion and exclusion criteria
Location
Research Site
Bronx, NY, United States, 10461
Location
Research Site
Philadelphia, PA, United States, 19104
Location
Research Site
Atlanta, GA, United States, 30308
Location
Research Site
Winston-Salem, NC, United States, 27157
Location
Research Site
Detroit, MI, United States, 48201
Location
Research Site
Saint Louis, MO, United States, 63110
Location
Research Site
Indianapolis, IN, United States, 46202
Location
Research Site
Morristown, NJ, United States, 07960
| Arms | Assigned Interventions |
|---|---|
| Experimental: First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractory Participants with recurrent or metastatic disease and were non-refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then every 8 weeks (Q8W) and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then every 4 weeks (Q4W) until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first. | Drug: MEDI0457 MEDI0457 7 mg will be administered intramuscularly followed by electroporation (EP) using CELLECTRA®5P device. Other Name: INO-3112 Device: CELLECTRA®5P device MEDI0457 7 mg will be administered intramuscularly followed by EP using CELLECTRA®5P device. Other Name: CELLECTRA 2000 Drug: Durvalumab Durvalumab will be administered intravenously at a dose of 1500 mg every 4 weeks. Other Name: MEDI4736 |
| Experimental: 1L R/M Platinum Refractory Participants with R/M disease and were refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first. | Drug: MEDI0457 MEDI0457 7 mg will be administered intramuscularly followed by electroporation (EP) using CELLECTRA®5P device. Other Name: INO-3112 Device: CELLECTRA®5P device MEDI0457 7 mg will be administered intramuscularly followed by EP using CELLECTRA®5P device. Other Name: CELLECTRA 2000 Drug: Durvalumab Durvalumab will be administered intravenously at a dose of 1500 mg every 4 weeks. Other Name: MEDI4736 |
| Experimental: Second-line (2L) + R/M Participants with R/M disease and were treated with 1 or more lines of platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first. | Drug: MEDI0457 MEDI0457 7 mg will be administered intramuscularly followed by electroporation (EP) using CELLECTRA®5P device. Other Name: INO-3112 Device: CELLECTRA®5P device MEDI0457 7 mg will be administered intramuscularly followed by EP using CELLECTRA®5P device. Other Name: CELLECTRA 2000 Drug: Durvalumab Durvalumab will be administered intravenously at a dose of 1500 mg every 4 weeks. Other Name: MEDI4736 |
Contacts
Contact
AstraZeneca Clinical Study Information Center
Investigators
Principal Investigator
MedImmune LLC
Study Director
%22%2F%3E%0A%3Cdefs%3E%0A%3Cpattern%20id%3D%22pattern0%22%20patternContentUnits%3D%22objectBoundingBox%22%20width%3D%221%22%20height%3D%221%22%3E%0A%3Cuse%20xlink%3Ahref%3D%22%23image0_8556_33445%22%20transform%3D%22translate(0%200.0591543)%20scale(0.00350877%200.0125956)%22%2F%3E%0A%3C%2Fpattern%3E%0A%3Cimage%20id%3D%22image0_8556_33445%22%20width%3D%22285%22%20height%3D%2270%22%20xlink%3Ahref%3D%22data%3Aimage%2Fpng%3Bbase64%2CiVBORw0KGgoAAAANSUhEUgAAAR0AAABGCAYAAADxVED7AAAAAXNSR0IArs4c6QAAE2xJREFUeF7tXY3xJUUR38nAIwHFBBQTQEhAMAE5E1BMQDABIAG9iwCMgCMCIQGBCCCDsX7r9FZvb%2Fd0z%2B68938cvVVXd3Vvdz56en7T31OWfJICSYGfNQVqrb8FAUopX9%2BDEOUenWQfSYGkwGNRoNb6i2VZ%2FrIsy1%2BXZcG%2F8fy4LMunpZSPbznaBJ1bUjfbTgo8IAVqrQCbjxjYyFG%2BKKU8v9XQE3RuRdlsNynwYBRo0s0ny7J8EBjaB6WUl4H3hl9J0BkmWX6QFPjpUaDW%2BqtlWb5clgV%2FR56vSylvRV4cfSdBZ5Ri%2BX5S4CdGgROAQzN8p5TyavZ0E3RmUzTbSwo8EAUuAA5m8VkpBYbmqU%2BCzlRyZmNJgcehwEXAwURelVLemT2jBJ3ZFM32kgIPQIEJgINZ%2FFhKeTZ7Ogk6syma7SUFnpgCkwCHZvFmKeW7mVNK0JlJzWwrKfDEFJgMOJjN81LKi5nTStCZSc1sKynwhBRocTj%2FGXCLR0b7YSnl08iL0XcSdKKUyveSAg9OgVorAGfNowo8ny3LAgnmcwekpkcnJ%2BgEVidfSQo8OgVqrYg0jrq3N%2Bml1opv8K31%2FLuU8t7M%2BSfozKRmtpUUeAIK1Fr%2F3nKpvN6R0AnA2Ww0tVYACqQd65kemZyg4y1T%2Fp4UeGAKtOTNqM3lLVm%2Bohmev%2B1M8btSypszSZCgM5Oa2VZS4I4UqLX%2BvuVTRXo1vVC11tppYHqsToJOZLnynaTAg1Fg0DXedXvXWiHpmImgpZSpODG1sQdblxxOUuC1pMBMwAGBaq3IPofUpD4JOq8lG%2BWkkgJxCgy4xkOBfbVWGJb%2F1BnB1KjklHTia51vJgWenAIDnqoQ4DRJB1UE4QGzngSdJ1%2F5HEBS4Ako4HiqIK1slf5G6uAEYnUSdJ5gvbPLpMCTUqDd2ICIY%2B1BIfUflLrHuN0BsTnfLMuCb7%2FXwKjWivKl%2F%2BpM8OBqv0KMVK%2BuUC%2B%2FTQrcgQIBwzHKilqApI0QYPQV6uUsy0LABBXrN4ZBeWoFwQSdOzBNdpEUuEIBz7u0LAuC93oBfl73KF0BAMIfSEVwnyNS%2Be327wQdj4L5e1LgdaFA0HCMQlsAHbq%2FCvlU%2BBMtwi7JRZLQF%2B0HRCVPq6mTks7rwp05j9eOAoEUBcx59VLVWpEKgfus8Kw2mBaxDHtNzx3u0Y2kICR%2BEgh533R%2FT9C5RL78OClwGwoEa%2BNsbnGREvFxKQU2mvVp4IXgP7jFz0o%2FaApGaQDPJQBK0LkNz2SrSYFLFAiUqjjE4TDbD8ABbm78vXsmST8cgF6OuOfxYYLOJdbIj5MC8ynguMc3lUoBFEgxZFDeSTvGu6R6XZF%2B0DSpYLiyBvagVK88IuTvSYFHokAnAfNQD0cBE7Lt4F3YdlwDcIvTgd3HzL8aoA9c9wAf80rilHQGqJmvJgVuTYFOoB5ABK7rriQhbEFflFLej4y52X3wKmxBVwzP1B0kLkhbB%2FBJ0ImsSL6TFLgTBQwpJwQ4NERRDTAUY1NrJbBZDcVN6gH4XFW9kMH%2BZy5xJejciZmym6SARwGjKNcQ4DDgQQlSBPhBvYKadTAq8%2FEoEhZyuVC8HYXe4YqPFnzXpgmp510CngQdjxPy96TAnSjQpA2Z7d01CFtDG1WzOmrderVwA0SAz9ki7RvwJOjciaGym6SARwGjSPqnpZQPvW%2B134Xk1L2%2FqlP6dFcjudl%2Bztp9viylvJugc2Y185ukwI0oYORZfVRKQSb58MMilbverI6bfpV0ZMcNpJCZPmLzQS3mNxJ0hpcxP0gK3JYChpoF2wyMwq4LXAEIKkdq2nc6KRdwf6v3adVagR8Anqi3C6Dzu2HQaciJFHh6IH49v%2B0yjLfedFoQ45vRiMnx3q5%2F0cbbu3%2FobCeo5h9ym57tIL%2BbT4GOGgMDL%2Bw8YfARpTFUN3oHdDy1DBnu%2Fw1SYBx0OgN75lnHg4O6%2FFobI8AG6Iys23DZxsudX2ggmNx3pofp9xadGUR%2Bc44CHfAZUrma%2BgSJB3vi8G2H%2F0yXe5N0%2FrksCyKbI8%2B3pZRfD0k6nbKGpyzskVGOvqMUmU7QmXxZ2uia5PvXKWCAD6QdAIgZ%2Fct7Fh6qHfCMChRMMh%2BJYl5xYhR0rPtxVGPTdVKPt5Cgc6BZSjrjbPSwX3TAB4crinB1H2Ev2oDH8F6pVwqfNCKvUg4GFwadwG2CochHjyhXf%2F%2Bpgs7VeeP7xpDIfaFiTvjvh5FCZ8wx2%2Fg%2FBQzwCdl7BPBAWoKk9AclAHBnz2nSDeKIVMNyZ23OBQcqmxk5IDxK8SGY%2B%2BcKOkb9lYeRQBMsbkOBs%2BBjeMjkILdbIE5KN2hvBzhhSacxNKrN80fWZb1853EjIPz%2B%2BIO4AvyBiNcN4RZ6q7w47G42nTZ%2BADFJGuscImLvVZZUwHbYxdqMjaA9xo%2Fvp5apvDpH%2Bb2gN8YLWrulFbxxNH4HHehQPcWL1I%2FSHn5Cm6Dv5fEakg%2Fo8aIX3%2BMAySpEXJBuVMAZAR15RQUm81wJZBpWsdrEEVoNjxNXCzhvYGEQmXkwmLWNwkOzpZiIBDYUm6YHILaVXWzGcd4v%2BtlAro0PY1vBpAijbFsUhIeTt0zjaaq4NuTq9DYHY2r0j5IG%2FAmtBZsfaKjRfzVWtmpxKvi3zc89GBuNWegC2peADBsEXLghQyjbXNw7KclEtV2Gad1oAfWhZxzFmMH%2F7pgbXcAXPd7GeLF2qMYXdoNbvKFIPq6xmZW2ANASWL1s92xh7a192WNRHP5Qzw48E7LpWOCieLNWMBrYLJ8M6oeH0ztwZ48czm6MSlbvKlJapwC%2F17kBHmJrRqIyzcWI0k1IdrxwE%2F3kqroNDBDYFc2lAe3f105mxd5HhxI2byRqNWqLALiObIKQW7ltVIxzxBPTlSRPbFi0h0A8eXicYQvN5uOCDzvEqLTpCD3oc2hE%2F%2BjNwwUdxZW2eUMa4%2FIq9GaZREU01gCHJAK8DnTFySg39C7r9hag006mrcYsHzuBTucuIpyEdGJZc5hiazHG4LbdGTskShL3QXeN6T6Qp7wGOq08wkiwYzcbutYKUJDxICTVYIlIHZKnchd4nHWEhEwnNQJiJUCrGeDGDQ54F7xB7Vn07QbjjSKQAqhYX%2FRx8HRdVKUwtEMZC228EdCRNhIpKVCINbXv2lAUoMBC4LtDtfn2LgCKM9PGoC1JjqrgE%2FNxoFptE2zyEOeRsr8%2BiqSD6F1zszDQkeEDWExIAgcR2YhvOmzeEwxF5Qvo05AdR5mzyoiGkfKQw6OADhhaU6XwrQXEmIOa3KjUC8Y8VRexYSBVaW0ATq9t8BVozh0oO3oY8S7gN4DfTtVo74K3OZiFD%2B4RflEk9510eUIy49270s3u4PYGbqkfbNNKe0%2FkpJVA1d2AwhWMDYIiQzvbCxvPkCFZmR9tDDRJfeFvMlSuoCJKPHZP6fa%2BvKRejYHw1oPNE7YHKY25dhzlFMbc8J1prFc28m6NO%2BEUaBMb7rBWHSPmbg7KAeUCq3GoHQqVnzG%2BN2kA%2FEvAA4CF5LBKiI1X%2Bc0LrslBMV%2B46nGUTxQNA%2FuVboVY16apwGdUqbB0EwYdJdX%2BsFEUFQvtd9Miaq3IwaAn5PVqY3E9QaMu80492pCYSx4U704gg06nLqY3MoJdRjVO4dAYaq2I%2F%2BEn%2FAYOZ4tPGZLGLsFQWZ%2BQhKjwgXYti7wVM0oLbFD8UQ8%2BdjBAgsGe6RqIlX3mHtxnQYeNDWsJp0vPAdLrBgcKaDpsg%2BqqV8rCWWKqlC68SvTDoBMl8iTQCQFOdExsoaWE914pBVJb%2BDlrx2mnMBgM4jw97inMxm5%2Ba4BOiIaK6gkvzqpuKO2Go6u9bxU%2BuflGtxZZCUkJHcRhphEvtkMLNrKz1QAh3UG9PeVtM0Fn5FTUdHqtBgdjYOiA3EYT8jJEiDwBdG7GfKNj0%2BariOKuusHoLqWVMOgp%2FLBtDG%2BD99ZNaXeTpsWtlWjGLLNg0Era3Xiwm%2FwtJEFFePDMO0L6X7iX9Ex7HYAb9QDypkzb68gYe6AjbTXbCWQssASSXnaqPPHR5FqT9Wqw1OjGPiu%2BjxCZbfohe5Psw%2FCKuHacJjUA5GWA51B1gFqrXGMeXoA1pafLK8q8uOTLvaOST0JzZfSWhna6ghcnPACYPyHV6sy6R76RfDgbdE6GBfChq8bwyNzkOz3QGToJRk4lJ4%2BLLm9fXc%2BjIDQBdNZ7oM8QU9lMFN1Lf8u7hVxPH9tAUDmkV82147Dv5UbDqTVaZ0fG3KySkhWnE6WhOOU56EiQQwzYiEgvA%2F1WSUkzNJdSnkXHe%2FW9pk7hECC%2BwL93HtqZoHMhhQFTXb15o5kBPRqpoKMYKle3oENsCgSj17p6aTD3gyYNEAhFrk4AnaHTn0kRFHH7dlMdIwGDIdC5YsdhoIP14dLI1b2D70lykG2HbUWNfpakw%2F9%2FxngpaHGqJ7E3sLaXwBMAfYo7i0T4TpG8mit82Njb5gTpBtI5ABFrHAri9BbKAh2pBnjtWL93xeFg2DlvO5JPMqTCXBFrT4xf0ikKOlLqDNtxGOhIdfnsmvLvKD9nOugYNsWrYybQkTwy3Y7XVGHQPHL4aPO6DDqGOh6h4S5uqxn7YQuiuQC0cYf5iNS59WuBjlU3JzJg%2Fk7oxGsMBvedzM%2Bx%2BjM33VVJJyrWBi64XxP6lmX5qmXaft9OCx7I6ILOFTsOJ57ilsXY3PwhZ8GxWV%2FdQr0ykoxPFSdnc0BNF%2BQU3Qx0OhHO8vDExgZPUBS4TKe5BDoXAEdV2c%2FkdFm8cwCdE2kFPb48FV3ZRFKKI9BSIUjtOlwidg%2FQ6QDOmsBoJe8pKqVXf1aTTsJ2HAE6UhoJu5%2B9k%2BYWoKOoXdM8Oso6TKFFB3CwDwDw4A8A9SEQ0wvC9dZArLUWOOo1AfDDIehdWwye5PanQ%2BkKryMNdKTHAHrdiGFV3gYYitdw9GIeRclfPbR9a9CxKqxZ%2BSyCGaQtwQQQEYVNzZxWA3o5dB6TeL%2FfEHRMl7c3pgA%2FwShOz5S4GIX30H7I6zMLdE5KOKOhCFCzgBNcdfyklPK3yLrsQGckNsdq3AuZjwxKe8c4RQ6u2TuAjpbv5F7b2k7uUBClUZBr2I4j6ai4vIeN5sbaTLfpNHpJWofjihzQ0VzmQ%2B54gw7S8B0yL7S5quEII%2FvFuKyv14SZZxbpV9lrIeCRoCOjTodPVkMXn8Xcbp7XHUBHnr5hdUc5zSz9WcvAn7EphpNzg8x3K9CR%2FDh0IjvAIzd5eB2DwIvXQuEXRlrLkE3HOKh6JNgSlJkLH141cuXjW5Jkftka4i5%2Bepf38UMp5Q2PZyToDMXmdKQdydyXFpT6iUQ%2B3wF05GnmGoPbSaa5rA90MVycs%2Bh3%2BVAJbrjwCd9oY7nMZa2gUzZCY8xwI3Oj%2FqW2DbU7BByGWhb6lu2NUe8k2ZUi7nsPR%2Bj3z0spf%2FRe3kBHIdppPVfJpzlITCwbt0aqsDXmdE%2B%2BO4COBGZ3g3VOoUgS4rC02TkMwGC8%2FhFeRTmOQ0kRRTWjUhWH8rG3sum0NZcHWOhub0rEtQJMDVPCSNuwCUHyWmlnSCuudNq5zncUdLQof2%2F%2Fz%2Fw9VEsHHXLQ6dbNGRmdoWKtC9D0TizYUO6VYdM5LIwCOp6HaAcinstcibwGaUxbQxu3rMFC5JSgczkex1sn5UBQC1HxdhTayxoyN1GvOhKit6bS0InxIrdql1xrrKVX9At8ixQKUj22ioqKzcyrLogQEbkXiPQh1YxJOlJd9Fhh1u%2FwyIGP3etvqMMVdHogcXZkSmLipo8bl8QD9MAUO5diOwm0FHxVvzdqpCCMG8wC3RS4skVojgYHdoLWaPy8MhzFHhEZsTC8bskmJd0oGI76lTVqtFPxEPDVqf8swfJmoNP4U3r98N9qdKwR8m%2Fd3wSe4LVx%2BDrtNlKjBeYJe5ssErc6Ejp3kIOvSZokPgTgEC%2BAZ2Bj4bzhSkniYLgn6ICPEX%2B2xmmNYgSBjtQHL8ctKJZ0npVsLXZ0%2FIiGVK8y7dxCSm13ayR7ko6h5kXGjcA2bBRew4WXcdBqHUfajbwjQadHf6q0yI2GvI8D2N9SvWInuQY8%2BJk2LM9l4uPtFilzJFG0w0vPSvvHQZIxDtTeGq2SZivFOhQ4KkBH2qgifBF9B2MEaAJokI5kFnyLNEigc4jNQWJcpAHrHaNolWR%2BMBKSIKOh4m7hoIAV%2FzLoNOCxYockSTa3pCJR8uTGu4FOYCNry2rS%2Fh6gM0hzGn8oRqYjTfW2gNm2obZpbW11aZTDcshTF4yEjm5pSrrG35BmTqU7WJ0Vdicxf%2Bd0gR6BvgAVJLvRs6tP3BabClRDFeF3DdE3VHw7jLIsZBvqFNe90RakC34FDewt2wnWqwMkiciM4dsVNe0dGvOurzbfXX%2FNkAvRHOPkAWtRBom8t5XTNOZgpaCQFAF6QbpUT7imAvPiYId17g2ySQfbens3irBSsbwOM76n1BOznK0zDuJFuZ6cF1dVyVMr2nri4Ab%2Fk9TIU2N2bbA8PurrK9w7FVlcdoigH%2FRJe8n7HHwq0zFwEF6SZLxO3cLsXgP5%2B%2BtFARazAXX4psw3g3JsvDDWTT2RedvtIr%2BHpwcDIEofouqARBtSn59sff8H57piU0311KcAAAAASUVORK5CYII%3D%22%2F%3E%0A%3C%2Fdefs%3E%0A%3C%2Fsvg%3E%0A)
