JOURNAL ONKOLOGIE – STUDIE
Combination Margetuximab, INCMGA00012, MGD013, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer (MAHOGANY)
Rekrutierend
NCT-Nummer:
NCT04082364
Studienbeginn:
September 2019
Letztes Update:
07.01.2021
Wirkstoff:
-
Indikation (Clinical Trials):
Stomach Neoplasms
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
-
Sponsor:
MacroGenics
Collaborator:
Zai Lab (Shanghai) Co., Ltd.
Studienleiter
Study Director
MacroGenics
Kontakt
Kontakt:
Phone: 240-660-0757
E-Mail: wortha@macrogenics.com» Kontaktdaten anzeigen
Kontakt:
Phone: 240-552-8069
E-Mail: wynterhortona@Macrogenics.com» Kontaktdaten anzeigen
Studienlocations (3 von 65)
Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)
60488 Frankfurt
(Hessen)
GermanyRekrutierend» Google-MapsHaematologisch-Onkologische Praxis Eppendorf
Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-MapsMayo Clinic - Scottsdale
85259 Scottsdale
United StatesRekrutierend» Google-Maps
60488 Frankfurt
(Hessen)
GermanyRekrutierend» Google-MapsHaematologisch-Onkologische Praxis Eppendorf
Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-MapsMayo Clinic - Scottsdale
85259 Scottsdale
United StatesRekrutierend» Google-Maps
City of Hope Comprehensive Cancer Center - Duarte
91010 Duarte
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Tina Zhang» Ansprechpartner anzeigenNorris Comprehensive Cancer Center (USC)
90033 Los Angeles
United StatesRekrutierend» Google-MapsUCLA School of Medicine
90404 Santa Monica
United StatesNoch nicht rekrutierend» Google-MapsYale University
06511 New Haven
United StatesRekrutierend» Google-MapsFlorida Cancer Specialists South
33901 Fort Myers
United StatesRekrutierend» Google-MapsMayo Clinic - Jacksonville
32224 Jacksonville
United StatesRekrutierend» Google-MapsOcala Oncology Center PL DBA Florida Cancer Affiliates - Ocala
34474 Ocala
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Anthony Joseph
Phone: 352-547-1954
E-Mail: anthony.joseph@usoncology.com» Ansprechpartner anzeigenFlorida Cancer Specialists North
33705 Saint Petersburg
United StatesRekrutierend» Google-MapsUniversity of Chicago
60637 Chicago
United StatesRekrutierend» Google-MapsEdward H. Kaplan MD & Associates
60076 Skokie
United StatesRekrutierend» Google-MapsMassachusetts General Hospital Cancer Center
02114 Boston
United StatesRekrutierend» Google-MapsHenry Ford Health System
48202 Detroit
United StatesRekrutierend» Google-MapsCancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
49503 Grand Rapids
United StatesAbgebrochen» Google-MapsMayo Clinic - Rochester
55905 Rochester
United StatesRekrutierend» Google-MapsWashington University School of Medicine
63110 Saint Louis
United StatesRekrutierend» Google-MapsNebraska Heme Onc
68506 Lincoln
United StatesRekrutierend» Google-MapsRutgers Cancer Institute of New Jersey
08903 New Brunswick
United StatesRekrutierend» Google-MapsThe University of New Mexico Comprehensive Cancer Center
87131 Albuquerque
United StatesRekrutierend» Google-MapsStephenson Cancer Center at OUHSC
73104 Oklahoma City
United StatesRekrutierend» Google-MapsOregon Health & Science University
97239 Portland
United StatesRekrutierend» Google-MapsSarah Cannon Research Institute
37203 Nashville
United StatesRekrutierend» Google-MapsOncology Consultants
77030 Houston
United StatesRekrutierend» Google-MapsUtah Cancer Specialists
84106 Salt Lake City
United StatesRekrutierend» Google-MapsVirginia Cancer Specialists
22031 Fairfax
United StatesRekrutierend» Google-MapsSwedish Cancer Institute
98104 Seattle
United StatesRekrutierend» Google-MapsBeijing Cancer Hospital
100142 Beijing
ChinaRekrutierend» Google-MapsJilin Cancer Hospital (Second People's Hospital Of Jilin Province)
130000 Changchun
ChinaNoch nicht rekrutierend» Google-MapsFujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)
350005 Fuzhou
ChinaNoch nicht rekrutierend» Google-MapsSIR RUN RUN SHAW Hospital, Zhejiang University school of medicine
310016 Hangzhou
ChinaNoch nicht rekrutierend» Google-MapsZhejiang Cancer Hospital
310022 Hangzhou
ChinaNoch nicht rekrutierend» Google-MapsAffiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin
150081 Harbin
ChinaNoch nicht rekrutierend» Google-MapsThe First Affiliated Hospital of Anhui Medical University
230022 Hefei
ChinaNoch nicht rekrutierend» Google-MapsAnhui Provincial Cancer Hospital
230031 Hefei
ChinaNoch nicht rekrutierend» Google-MapsJinan Center Hospital
250013 Jinan
ChinaNoch nicht rekrutierend» Google-MapsNanjing University Medical School; Nanjing Drug Tower
210000 Nanjing
ChinaNoch nicht rekrutierend» Google-MapsZhongshan Hospital Fudan University
200433 Shanghai
ChinaNoch nicht rekrutierend» Google-MapsLiaoning cancer hospital
110042 Shenyang
ChinaNoch nicht rekrutierend» Google-MapsHebei cancer hospital (The Fourth Affiliate)
050000 Shijiazhuang
ChinaNoch nicht rekrutierend» Google-MapsWuhan Union Hospital
430022 Wuhan
ChinaNoch nicht rekrutierend» Google-MapsHenan Cancer Hospital
450008 Zhengzhou
ChinaNoch nicht rekrutierend» Google-MapsThe First Affiliated Hospital of Zhengzhou University
450052 Zhenzhou
ChinaNoch nicht rekrutierend» Google-MapsOspedale San Raffaele
20132 Milan
ItalyRekrutierend» Google-MapsAzienda Ospedaliero-Universitaria Pisana
56126 Pisa
ItalyNoch nicht rekrutierend» Google-MapsHallym University Sacred Heart Hospital
14068 Anyang-Si
Korea, Republic ofNoch nicht rekrutierend» Google-MapsCHA bundang
Gyeonggi-do
Korea, Republic ofRekrutierend» Google-MapsInje University Haeundae Paik Hospital
Haeundae
Korea, Republic ofRekrutierend» Google-MapsSeoul National University Bundang Hospital
Seongnam-si
Korea, Republic ofRekrutierend» Google-MapsAsan Medical Center
Seoul
Korea, Republic ofRekrutierend» Google-MapsKorea University Guro
Seoul
Korea, Republic ofRekrutierend» Google-MapsKorea University, Anam Hospital
Seoul
Korea, Republic ofRekrutierend» Google-MapsSamsung Medical Center
Seoul
Korea, Republic ofRekrutierend» Google-MapsSeoul National University Hospital
Seoul
Korea, Republic ofRekrutierend» Google-MapsYonsei University College of Medicine (Severance Hospital)
Seoul
Korea, Republic ofRekrutierend» Google-MapsCatholic University of Korea St. Vincent Hospital
Suwon
Korea, Republic ofRekrutierend» Google-MapsCentrum Medyczne MrukMed
35-922 Rzeszów
PolandRekrutierend» Google-MapsNational University Hospital (Cancer Institute) -Singapore
119074 Singapore
SingaporeRekrutierend» Google-MapsNational Cancer Center Singapore
169610 Singapore
SingaporeRekrutierend» Google-MapsTaipei Medical University Hospital
110 Taipei City
TaiwanRekrutierend» Google-MapsKaohsiung Chang Gung MemorialHospital
83301 Kaohsiung
TaiwanRekrutierend» Google-MapsChang Gung Memorial Hospital, Keelung
204 Keelung
TaiwanRekrutierend» Google-MapsLiuying Chi MeiMedical Hospital
73657 Tainan city
TaiwanRekrutierend» Google-MapsNational Taiwan University
Taipei
TaiwanRekrutierend» Google-Maps
Alle anzeigen 91010 Duarte
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Tina Zhang» Ansprechpartner anzeigenNorris Comprehensive Cancer Center (USC)
90033 Los Angeles
United StatesRekrutierend» Google-MapsUCLA School of Medicine
90404 Santa Monica
United StatesNoch nicht rekrutierend» Google-MapsYale University
06511 New Haven
United StatesRekrutierend» Google-MapsFlorida Cancer Specialists South
33901 Fort Myers
United StatesRekrutierend» Google-MapsMayo Clinic - Jacksonville
32224 Jacksonville
United StatesRekrutierend» Google-MapsOcala Oncology Center PL DBA Florida Cancer Affiliates - Ocala
34474 Ocala
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Anthony Joseph
Phone: 352-547-1954
E-Mail: anthony.joseph@usoncology.com» Ansprechpartner anzeigenFlorida Cancer Specialists North
33705 Saint Petersburg
United StatesRekrutierend» Google-MapsUniversity of Chicago
60637 Chicago
United StatesRekrutierend» Google-MapsEdward H. Kaplan MD & Associates
60076 Skokie
United StatesRekrutierend» Google-MapsMassachusetts General Hospital Cancer Center
02114 Boston
United StatesRekrutierend» Google-MapsHenry Ford Health System
48202 Detroit
United StatesRekrutierend» Google-MapsCancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
49503 Grand Rapids
United StatesAbgebrochen» Google-MapsMayo Clinic - Rochester
55905 Rochester
United StatesRekrutierend» Google-MapsWashington University School of Medicine
63110 Saint Louis
United StatesRekrutierend» Google-MapsNebraska Heme Onc
68506 Lincoln
United StatesRekrutierend» Google-MapsRutgers Cancer Institute of New Jersey
08903 New Brunswick
United StatesRekrutierend» Google-MapsThe University of New Mexico Comprehensive Cancer Center
87131 Albuquerque
United StatesRekrutierend» Google-MapsStephenson Cancer Center at OUHSC
73104 Oklahoma City
United StatesRekrutierend» Google-MapsOregon Health & Science University
97239 Portland
United StatesRekrutierend» Google-MapsSarah Cannon Research Institute
37203 Nashville
United StatesRekrutierend» Google-MapsOncology Consultants
77030 Houston
United StatesRekrutierend» Google-MapsUtah Cancer Specialists
84106 Salt Lake City
United StatesRekrutierend» Google-MapsVirginia Cancer Specialists
22031 Fairfax
United StatesRekrutierend» Google-MapsSwedish Cancer Institute
98104 Seattle
United StatesRekrutierend» Google-MapsBeijing Cancer Hospital
100142 Beijing
ChinaRekrutierend» Google-MapsJilin Cancer Hospital (Second People's Hospital Of Jilin Province)
130000 Changchun
ChinaNoch nicht rekrutierend» Google-MapsFujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)
350005 Fuzhou
ChinaNoch nicht rekrutierend» Google-MapsSIR RUN RUN SHAW Hospital, Zhejiang University school of medicine
310016 Hangzhou
ChinaNoch nicht rekrutierend» Google-MapsZhejiang Cancer Hospital
310022 Hangzhou
ChinaNoch nicht rekrutierend» Google-MapsAffiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin
150081 Harbin
ChinaNoch nicht rekrutierend» Google-MapsThe First Affiliated Hospital of Anhui Medical University
230022 Hefei
ChinaNoch nicht rekrutierend» Google-MapsAnhui Provincial Cancer Hospital
230031 Hefei
ChinaNoch nicht rekrutierend» Google-MapsJinan Center Hospital
250013 Jinan
ChinaNoch nicht rekrutierend» Google-MapsNanjing University Medical School; Nanjing Drug Tower
210000 Nanjing
ChinaNoch nicht rekrutierend» Google-MapsZhongshan Hospital Fudan University
200433 Shanghai
ChinaNoch nicht rekrutierend» Google-MapsLiaoning cancer hospital
110042 Shenyang
ChinaNoch nicht rekrutierend» Google-MapsHebei cancer hospital (The Fourth Affiliate)
050000 Shijiazhuang
ChinaNoch nicht rekrutierend» Google-MapsWuhan Union Hospital
430022 Wuhan
ChinaNoch nicht rekrutierend» Google-MapsHenan Cancer Hospital
450008 Zhengzhou
ChinaNoch nicht rekrutierend» Google-MapsThe First Affiliated Hospital of Zhengzhou University
450052 Zhenzhou
ChinaNoch nicht rekrutierend» Google-MapsOspedale San Raffaele
20132 Milan
ItalyRekrutierend» Google-MapsAzienda Ospedaliero-Universitaria Pisana
56126 Pisa
ItalyNoch nicht rekrutierend» Google-MapsHallym University Sacred Heart Hospital
14068 Anyang-Si
Korea, Republic ofNoch nicht rekrutierend» Google-MapsCHA bundang
Gyeonggi-do
Korea, Republic ofRekrutierend» Google-MapsInje University Haeundae Paik Hospital
Haeundae
Korea, Republic ofRekrutierend» Google-MapsSeoul National University Bundang Hospital
Seongnam-si
Korea, Republic ofRekrutierend» Google-MapsAsan Medical Center
Seoul
Korea, Republic ofRekrutierend» Google-MapsKorea University Guro
Seoul
Korea, Republic ofRekrutierend» Google-MapsKorea University, Anam Hospital
Seoul
Korea, Republic ofRekrutierend» Google-MapsSamsung Medical Center
Seoul
Korea, Republic ofRekrutierend» Google-MapsSeoul National University Hospital
Seoul
Korea, Republic ofRekrutierend» Google-MapsYonsei University College of Medicine (Severance Hospital)
Seoul
Korea, Republic ofRekrutierend» Google-MapsCatholic University of Korea St. Vincent Hospital
Suwon
Korea, Republic ofRekrutierend» Google-MapsCentrum Medyczne MrukMed
35-922 Rzeszów
PolandRekrutierend» Google-MapsNational University Hospital (Cancer Institute) -Singapore
119074 Singapore
SingaporeRekrutierend» Google-MapsNational Cancer Center Singapore
169610 Singapore
SingaporeRekrutierend» Google-MapsTaipei Medical University Hospital
110 Taipei City
TaiwanRekrutierend» Google-MapsKaohsiung Chang Gung MemorialHospital
83301 Kaohsiung
TaiwanRekrutierend» Google-MapsChang Gung Memorial Hospital, Keelung
204 Keelung
TaiwanRekrutierend» Google-MapsLiuying Chi MeiMedical Hospital
73657 Tainan city
TaiwanRekrutierend» Google-MapsNational Taiwan University
Taipei
TaiwanRekrutierend» Google-Maps
Studien-Informationen
Detailed Description:A single-arm cohort (Cohort A, 40 to 110 patients) will evaluate safety and efficacy of
margetuximab plus INCMGA00012. In a 4-arm cohort (Cohort B Part 1, 50 patients per arm),
patients will be randomized to margetuximab plus chemotherapy plus INCMGA00012, margetuximab
plus chemotherapy plus MGD013, margetuximab plus chemotherapy, or trastuzumab plus
chemotherapy. A checkpoint inhibitor (CPI) (INCMGA00012 or MGD013) will be selected from
Cohort B Part 1 and evaluated in a randomized 2-arm cohort (Cohort B Part 2, 250 patients per
arm) of margetuximab plus chemotherapy plus INCMGA00012 or MGD013, or trastuzumab plus
chemotherapy.
Ein-/Ausschlusskriterien
Key Inclusion Criteria:- Histologically confirmed diagnosis of previously untreated locally advanced
unresectable or metastatic HER2+ GC or GEJ adenocarcinoma
1. Prior systemic perioperative treatment is allowed; however the patient must have
had a disease-free interval of at least 6 months from end of chemo/surgery
2. Patients receiving perioperative anti-HER2 therapy require testing of HER2 status
for eligibility
3. Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥
1%) per central review
4. Cohort B: HER2-positive (by IHC 3+ or IHC 2+ in combination with FISH+) by local
review. PD -L1 status is not required for enrollment.
- Availability of formalin-fixed, paraffin-embedded tumor specimen, unstained slides or
contemporaneous biopsy for tumor target testing
- Eastern Cooperative Oncology Group performance status of 0 or 1, verified within 3
days of Day 1
- Life expectancy ≥ 6 months
- At least one radiographically measurable target lesion
- Acceptable laboratory parameters and adequate organ function
Key Exclusion Criteria:
- Other malignancy that is progressing or required treatment within the past 5 years,
with certain exceptions
- Patients with known MSI-H status
- History of allogeneic stem cell or tissue/solid organ transplant
- Central nervous system metastases
- Clinically significant cardiovascular disease, gastrointestinal disorders, pulmonary
compromise
- Prior neoadjuvant or adjuvant treatment with immunotherapy
Studien-Rationale
Primary outcome:1. Incidence of Adverse Events of margetuximab plus INCMGA00012 as assessed by CTCAE v5.0 (Time Frame - 6 month intervals):
Evaluation of adverse events and serious adverse events (Cohort A)
2. Objective response rate (ORR) for non-microsatellite instability-high (non-MSI-H) patients (Cohort A) (Time Frame - 3 years):
Proportion of non MSI-H patients with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A and B)
3. Overall survival (Time Frame - Up to 3 years):
Time from randomization to death from any cause (Cohort B)
Secondary outcome:
1. Progression-free survival (Time Frame - Up to 3 years):
Time from start of study treatment to the first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurs first. (Cohorts A and B)
2. Duration of response (Time Frame - Up to 3 years):
Time from the date of initial response (CR or PR) to the date of first documented progression or death from any cause, whichever occurs first (Cohorts A and B)
3. Disease control rate (Time Frame - Up to 3 years):
Percentage of patients who experienced response of CR, PR or stable disease for at least 3 months from start of study treatment (Cohorts A and B)
4. Patient reported quality of life (Time Frame - Up to 3 years):
Quality of life as assessed using the Functional Assessment of Cancer Therapy - Gastric Questionnaire (FACT-Ga) (Cohort B) on a scale of 0 to 184. Lower scores correlate with worse quality of life and higher scores correlate with better quality of life.
Studien-Arme
- Experimental: Margetuximab plus INCMGA00012
margetuximab plus INCMGA00012 - Experimental: Margetuximab plus INCMGA00012 plus chemo
margetuximab plus INCMGA00012 plus capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) - Experimental: Margetuximab plus MGD013 plus chemo
margetuximab plus MGD013 plus XELOX or mFOLFOX-6 - Experimental: Margetuximab plus chemo
margetuximab plus XELOX or mFOLFOX-6 - Active Comparator: Control Arm
Trastuzumab plus XELOX or mFOLFOX-6
Geprüfte Regime
- margetuximab plus INCMGA00012 (MGAH22 / MGA012 / ):
margetuximab: Fc-modified anti-HER2 monoclonal antibody: • 15 mg/kg IV Day1 of each 3 week cycle INCMGA00012: anti-PD-1 checkpoint inhibitor: • 375 mg IV Day 1 of each 3 week cycle - Margetuximab plus INCMGA00012 plus chemo (MGAH22 / MGA012 / ):
margetuximab: Fc-modified anti-HER2 monoclonal antibody • 15 mg/kg IV Day1 of each 3 week cycle INCMGA00012: anti-PD-1 checkpoint inhibitor • 375 mg IV Day 1 of each 3 week cycle Chemotherapy Drug Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, administered as part of XELOX chemotherapy Drug Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion, administered as part of XELOX chemotherapy Drug Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy Drug 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy Drug 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, as part of mFOLFOX-6 Drug Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy - Margetuximab plus MGD013 plus chemo (MGAH22):
margetuximab: Fc-modified anti-HER2 monoclonal antibody • 15 mg/kg IV Day1 of each 3 week cycle MGD013: Anti-PD-1, anti-LAG-3 dual checkpoint inhibitor DART molecule • Dosing regimen located in the protocol Chemotherapy Drug Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, administered as part of XELOX chemotherapy Drug Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion, administered as part of XELOX chemotherapy Drug Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy Drug 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy Drug 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, as part of mFOLFOX-6 Drug Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy - Margetuximab plus chemo (MGAH22):
margetuximab: Fc-modified anti-HER2 monoclonal antibody • 15 mg/kg IV Day1 of each 3 week cycle Chemotherapy Drug Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, administered as part of XELOX chemotherapy Drug Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion, administered as part of XELOX chemotherapy Drug Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy Drug 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy Drug 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, as part of mFOLFOX-6 Drug Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy - Trastuzumab plus chemo (Herceptin):
Anti-HER2 monoclonal antibody • 8 mg/kg loading dose and then 6 mg/kg administered IV on Day 1 of each 3 week cycle Chemotherapy Drug Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, administered as part of XELOX chemotherapy Drug Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion, administered as part of XELOX chemotherapy Drug Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy Drug 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy Drug 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, as part of mFOLFOX-6 Drug Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion, administered as part of mFOLFOX-6 chemotherapy
Quelle: ClinicalTrials.gov