Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer
- Conditions
- Gastric CancerGastroesophageal Junction CancerHER2-positive Gastric Cancer
- Interventions
- Registration Number
- NCT04082364
- Lead Sponsor
- MacroGenics
- Brief Summary
This is a Phase 2/3, randomized, open-label study for the treatment of patients with HER2-positive Gastric cancer (GC) or Gastroesophageal Junction (GEJ) cancer conducted in two parts.
Part A is a single-arm cohort (Cohort A, 40 to 110 participants) will evaluate safety and efficacy of margetuximab plus retifanlimab.
Part B Part 1 has 4 arms (50 patients/arm). Participants will be randomized to margetuximab plus retifanlimab plus chemotherapy, margetuximab plus tebotelimab, plus chemotherapy, margetuximab plus chemotherapy, or trastuzumab plus chemotherapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
-
Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma
- Prior systemic perioperative treatment is allowed; however the participants must have had a disease-free interval of at least 6 months from end of chemo/surgery
- Participants receiving perioperative anti-HER2 therapy require testing of HER2 status for eligibility
- Cohort A: HER2-positive (by IHC 3+) and PD-L1-positive (by IHC with 22C3 CPS ≥ 1%) per central review
- 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
-
Other malignancy that is progressing or required treatment within the past 5 years, with certain exceptions
- Participants 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Chemotherapy-free arm margetuximab margetuximab plus retifanlimab Chemotherapy-free arm Retifanlimab margetuximab plus retifanlimab Margetuximab, retifanlimab, and chemotherapy arm Retifanlimab margetuximab plus retifanlimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Trastuzumab and chemotherapy arm Chemotherapy Trastuzumab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Margetuximab, retifanlimab, and chemotherapy arm margetuximab margetuximab plus retifanlimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Margetuximab, retifanlimab, and chemotherapy arm Chemotherapy margetuximab plus retifanlimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Margetuximab, tebotelimab and chemotherapy arm margetuximab margetuximab plus tebotelimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Margetuximab, tebotelimab and chemotherapy arm Tebotelimab margetuximab plus tebotelimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Margetuximab, tebotelimab and chemotherapy arm Chemotherapy margetuximab plus tebotelimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Margetuximab and chemotherapy arm margetuximab margetuximab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Margetuximab and chemotherapy arm Chemotherapy margetuximab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6) Trastuzumab and chemotherapy arm Trastuzumab Trastuzumab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events of Margetuximab Plus Retifanlimab in Cohort A, as Assessed by CTCAE v5.0 Throughout the study, an average of 11 months. Evaluation of adverse events and serious adverse events (Cohort A)
Objective Response Rate (ORR) for Non-microsatellite Instability-high (Non-MSI-H) Participants (Cohort A) Using Investigator-assessed Radiology Reviews Throughout the study, an average of 11 months. Percent of non MSI-H participants with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A ) based on investigator assessment.
CR is defined as the disappearance of all target and non-target lesions with no new lesions appearing PR is defined as \>= to a 30% decrease in the sum of the longest dimensions of target lesions, non-progression of non- target lesions, with no new lesions appearing.
CR + PR = ORR
- Secondary Outcome Measures
Name Time Method Median Progression-free Survival Using Investigator-assessed Radiology Reviews in Cohort A Throughout the study, an average of 11 months. 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) based on investigator assessment
Median Duration of Response in Cohort A Using Investigator-assessed Radiology Reviews Throughout the study, an average of 11 months. 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)
Disease Control Rate Throughout the study, an average of 11 months. 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)
ORR for Cohort B Throughout the study, an average of 11 months. Proportion of participants with best overall response of CR plus PR per RECIST 1.1
Number of Participants Who Have Antidrug Antibodies (ADA) to Margetuximab Throughout the study, an average of 11 months. Number of Participants Who Have ADA to Retifanlimab Throughout the study, an average of 11 months. Number of Participants Who Have ADA to Tebotelimab Throughout the study, an average of 11 months.
Trial Locations
- Locations (73)
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Mayo Clinic - Scottsdale
🇺🇸Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center - Duarte
🇺🇸Duarte, California, United States
Norris Comprehensive Cancer Center (USC)
🇺🇸Los Angeles, California, United States
UCLA School of Medicine
🇺🇸Santa Monica, California, United States
Salinas Memorial
🇺🇸Salinas, California, United States
Florida Cancer Specialists South
🇺🇸Fort Myers, Florida, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala
🇺🇸Ocala, Florida, United States
Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
🇺🇸Grand Rapids, Michigan, United States
Florida Cancer Specialists North
🇺🇸Saint Petersburg, Florida, United States
Azienda Ospedaliero-Universitaria Pisana
🇮🇹Pisa, Italy
University of Chicago
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
SIR RUN RUN SHAW Hospital, Zhejiang University school of medicine
🇨🇳Hangzhou, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, China
Anhui Provincial Cancer Hospital
🇨🇳Hefei, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhenzhou, China
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Stephenson Cancer Center at OUHSC
🇺🇸Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Oncology Consultants
🇺🇸Houston, Texas, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
SPSK nr 1 in Lublin
🇵🇱Lublin, Poland
Kaohsiung Chang Gung MemorialHospital
🇨🇳Kaohsiung, Taiwan
National Cancer Center Singapore
🇸🇬Singapore, Singapore
Liuying Chi MeiMedical Hospital
🇨🇳Tainan city, Taiwan
Chang Gung Memorial Hospital, Keelung
🇨🇳Keelung, Taiwan
National Taiwan University
🇨🇳Taipei, Taiwan
Centrum Medyczne MrukMed
🇵🇱Rzeszów, Poland
Taipei Medical University Hospital
🇨🇳Taipei City, Taipei, Taiwan
Edward H. Kaplan MD & Associates
🇺🇸Skokie, Illinois, United States
Nebraska Heme Onc
🇺🇸Lincoln, Nebraska, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Beijing Cancer Hospital
🇨🇳Beijing, China
Jilin Cancer Hospital (Second People's Hospital Of Jilin Province)
🇨🇳Changchun, China
Affiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin
🇨🇳Harbin, China
Fujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)
🇨🇳Fuzhou, China
Hebei cancer hospital (The Fourth Affiliate)
🇨🇳Shijiazhuang, China
Jinan Center Hospital
🇨🇳Jinan, China
Wuhan Union Hospital
🇨🇳Wuhan, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Liaoning cancer hospital
🇨🇳Shenyang, China
Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)
🇩🇪Frankfurt, Germany
Haematologisch-Onkologische Praxis Eppendorf
🇩🇪Hamburg, Germany
Korea University, Anam Hospital
🇰🇷Seoul, Korea, Republic of
Istituto Europeo Di Oncologia
🇮🇹Milan, Italy
Universitätsmedizin Mainz
🇩🇪Mainz, Germany
Ospedale San Raffaele
🇮🇹Milan, Italy
Kliniken Maria Hilf GmbH
🇩🇪Monchengladbach, Germany
CHA bundang
🇰🇷Gyeonggi-do, Korea, Republic of
Inje University Haeundae Paik Hospital
🇰🇷Haeundae, Korea, Republic of
Hallym University Sacred Heart Hospital
🇰🇷Anyang-Si, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Guro
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Catholic University of Korea St. Vincent Hospital
🇰🇷Suwon, Korea, Republic of
Yonsei University College of Medicine (Severance Hospital)
🇰🇷Seoul, Korea, Republic of
National University Hospital (Cancer Institute) -Singapore
🇸🇬Singapore, Singapore
The Christie Hospital NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Kaiser Permanente
🇺🇸Honolulu, Hawaii, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
The University of New Mexico Comprehensive Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Nanjing University Medical School; Nanjing Drug Tower
🇨🇳Nanjing, China