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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

Minori K. Rosales, MD, PhD
Study Director
MacroGenics

Kontakt

Studienlocations (3 von 65)

Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)
60488 Frankfurt
(Hessen)
GermanyRekrutierend» Google-Maps
Haematologisch-Onkologische Praxis Eppendorf
Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-Maps
Mayo Clinic - Scottsdale
85259 Scottsdale
United StatesRekrutierend» Google-Maps
Norris Comprehensive Cancer Center (USC)
90033 Los Angeles
United StatesRekrutierend» Google-Maps
UCLA School of Medicine
90404 Santa Monica
United StatesNoch nicht rekrutierend» Google-Maps
Florida Cancer Specialists South
33901 Fort Myers
United StatesRekrutierend» Google-Maps
Mayo Clinic - Jacksonville
32224 Jacksonville
United StatesRekrutierend» Google-Maps
Ocala 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 anzeigen
Florida Cancer Specialists North
33705 Saint Petersburg
United StatesRekrutierend» Google-Maps
Edward H. Kaplan MD & Associates
60076 Skokie
United StatesRekrutierend» Google-Maps
Massachusetts General Hospital Cancer Center
02114 Boston
United StatesRekrutierend» Google-Maps
Henry Ford Health System
48202 Detroit
United StatesRekrutierend» Google-Maps
Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
49503 Grand Rapids
United StatesAbgebrochen» Google-Maps
Mayo Clinic - Rochester
55905 Rochester
United StatesRekrutierend» Google-Maps
Washington University School of Medicine
63110 Saint Louis
United StatesRekrutierend» Google-Maps
Rutgers Cancer Institute of New Jersey
08903 New Brunswick
United StatesRekrutierend» Google-Maps
The University of New Mexico Comprehensive Cancer Center
87131 Albuquerque
United StatesRekrutierend» Google-Maps
Stephenson Cancer Center at OUHSC
73104 Oklahoma City
United StatesRekrutierend» Google-Maps
Oregon Health & Science University
97239 Portland
United StatesRekrutierend» Google-Maps
Sarah Cannon Research Institute
37203 Nashville
United StatesRekrutierend» Google-Maps
Utah Cancer Specialists
84106 Salt Lake City
United StatesRekrutierend» Google-Maps
Virginia Cancer Specialists
22031 Fairfax
United StatesRekrutierend» Google-Maps
Swedish Cancer Institute
98104 Seattle
United StatesRekrutierend» Google-Maps
Jilin Cancer Hospital (Second People's Hospital Of Jilin Province)
130000 Changchun
ChinaNoch nicht rekrutierend» Google-Maps
Fujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)
350005 Fuzhou
ChinaNoch nicht rekrutierend» Google-Maps
SIR RUN RUN SHAW Hospital, Zhejiang University school of medicine
310016 Hangzhou
ChinaNoch nicht rekrutierend» Google-Maps
Zhejiang Cancer Hospital
310022 Hangzhou
ChinaNoch nicht rekrutierend» Google-Maps
Affiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin
150081 Harbin
ChinaNoch nicht rekrutierend» Google-Maps
The First Affiliated Hospital of Anhui Medical University
230022 Hefei
ChinaNoch nicht rekrutierend» Google-Maps
Anhui Provincial Cancer Hospital
230031 Hefei
ChinaNoch nicht rekrutierend» Google-Maps
Jinan Center Hospital
250013 Jinan
ChinaNoch nicht rekrutierend» Google-Maps
Nanjing University Medical School; Nanjing Drug Tower
210000 Nanjing
ChinaNoch nicht rekrutierend» Google-Maps
Zhongshan Hospital Fudan University
200433 Shanghai
ChinaNoch nicht rekrutierend» Google-Maps
Liaoning cancer hospital
110042 Shenyang
ChinaNoch nicht rekrutierend» Google-Maps
Hebei cancer hospital (The Fourth Affiliate)
050000 Shijiazhuang
ChinaNoch nicht rekrutierend» Google-Maps
Wuhan Union Hospital
430022 Wuhan
ChinaNoch nicht rekrutierend» Google-Maps
Henan Cancer Hospital
450008 Zhengzhou
ChinaNoch nicht rekrutierend» Google-Maps
The First Affiliated Hospital of Zhengzhou University
450052 Zhenzhou
ChinaNoch nicht rekrutierend» Google-Maps
Azienda Ospedaliero-Universitaria Pisana
56126 Pisa
ItalyNoch nicht rekrutierend» Google-Maps
Hallym University Sacred Heart Hospital
14068 Anyang-Si
Korea, Republic ofNoch nicht rekrutierend» Google-Maps
Inje University Haeundae Paik Hospital
Haeundae
Korea, Republic ofRekrutierend» Google-Maps
Seoul National University Bundang Hospital
Seongnam-si
Korea, Republic ofRekrutierend» Google-Maps
Korea University, Anam Hospital
Seoul
Korea, Republic ofRekrutierend» Google-Maps
Seoul National University Hospital
Seoul
Korea, Republic ofRekrutierend» Google-Maps
Yonsei University College of Medicine (Severance Hospital)
Seoul
Korea, Republic ofRekrutierend» Google-Maps
Catholic University of Korea St. Vincent Hospital
Suwon
Korea, Republic ofRekrutierend» Google-Maps
National University Hospital (Cancer Institute) -Singapore
119074 Singapore
SingaporeRekrutierend» Google-Maps
National Cancer Center Singapore
169610 Singapore
SingaporeRekrutierend» Google-Maps
Taipei Medical University Hospital
110 Taipei City
TaiwanRekrutierend» Google-Maps
Kaohsiung Chang Gung MemorialHospital
83301 Kaohsiung
TaiwanRekrutierend» Google-Maps
Chang Gung Memorial Hospital, Keelung
204 Keelung
TaiwanRekrutierend» Google-Maps
Liuying Chi MeiMedical Hospital
73657 Tainan city
TaiwanRekrutierend» Google-Maps
Alle anzeigen

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


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