Clinical trial NCT04082364: Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer
Official title: A Phase 2/3 Trial to Evaluate Margetuximab in Combination With INCMGA00012 and Chemotherapy or MGD013 and Chemotherapy in Patients With Metastatic or Locally Advanced, Treatment-naïve, HER2-Positive Gastric or Gastroesophageal Junction Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Gastric Cancer
Gastroesophageal Junction Cancer
HER2-positive Gastric Cancer
Lead sponsor: MacroGenics
Sponsor class: INDUSTRY
Collaborators: name: Zai Lab (Shanghai) Co., Ltd.
First posted: 2019-09-09
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cohort A is a single-arm cohort to evaluate safety and efficacy of margetuximab plus retifanlimab. Cohort B Part 1 is a randomized, 4-arm segment to evaluate margetuximab plus retifanlimab plus chemotherapy, margetuximab plus tebotelimab plus chemotherapy, margetuximab plus chemotherapy, vs trastuzumab plus chemotherapy.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 participants must have had a disease-free interval of at least 6 months from end of chemo/surgery
  2. Participants 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

  * 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

Primary outcomes:
measure: Number of Participants With Adverse Events of Margetuximab Plus Retifanlimab in Cohort A, as Assessed by CTCAE v5.0
timeFrame: Throughout the study, an average of 11 months.
measure: Objective Response Rate (ORR) for Non-microsatellite Instability-high (Non-MSI-H) Participants (Cohort A) Using Investigator-assessed Radiology Reviews
timeFrame: Throughout the study, an average of 11 months.
Secondary outcomes:
measure: Median Progression-free Survival Using Investigator-assessed Radiology Reviews in Cohort A
timeFrame: Throughout the study, an average of 11 months.
measure: Median Duration of Response in Cohort A Using Investigator-assessed Radiology Reviews
timeFrame: Throughout the study, an average of 11 months.
measure: Disease Control Rate
timeFrame: Throughout the study, an average of 11 months.
measure: ORR for Cohort B
timeFrame: Throughout the study, an average of 11 months.
measure: Number of Participants Who Have Antidrug Antibodies (ADA) to Margetuximab
timeFrame: Throughout the study, an average of 11 months.
measure: Number of Participants Who Have ADA to Retifanlimab
timeFrame: Throughout the study, an average of 11 months.
measure: Number of Participants Who Have ADA to Tebotelimab
timeFrame: Throughout the study, an average of 11 months.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Scottsdale
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center - Duarte
state: California
city: Los Angeles
country: United States
facility: Norris Comprehensive Cancer Center (USC)
state: California
city: Salinas
country: United States
facility: Salinas Memorial
state: California
city: Santa Monica
country: United States
facility: UCLA School of Medicine
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists South
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists North
state: Florida
city: Honolulu
country: United States
facility: Kaiser Permanente
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Skokie
country: United States
facility: Edward H. Kaplan MD & Associates
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Heme Onc
state: Nebraska
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: The University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center at OUHSC
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: Oncology Consultants
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital (Second People's Hospital Of Jilin Province)
city: Fuzhou
country: China
facility: Fujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)
city: Hangzhou
country: China
facility: SIR RUN RUN SHAW Hospital, Zhejiang University school of medicine
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Affiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
city: Jinan
country: China
facility: Jinan Center Hospital
city: Nanjing
country: China
facility: Nanjing University Medical School; Nanjing Drug Tower
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shenyang
country: China
facility: Liaoning cancer hospital
city: Shijiazhuang
country: China
facility: Hebei cancer hospital (The Fourth Affiliate)
city: Wuhan
country: China
facility: Wuhan Union Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Zhenzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Frankfurt
country: Germany
facility: Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)
city: Hamburg
country: Germany
facility: Haematologisch-Onkologische Praxis Eppendorf
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Monchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Milan
country: Italy
facility: Istituto Europeo Di Oncologia
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Anyang-Si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA bundang
city: Haeundae
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro
city: Seoul
country: Korea, Republic of
facility: Korea University, Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University College of Medicine (Severance Hospital)
city: Suwon
country: Korea, Republic of
facility: Catholic University of Korea St. Vincent Hospital
city: Lublin
country: Poland
facility: SPSK nr 1 in Lublin
city: Rzeszów
country: Poland
facility: Centrum Medyczne MrukMed
city: Singapore
country: Singapore
facility: National University Hospital (Cancer Institute) -Singapore
city: Singapore
country: Singapore
facility: National Cancer Center Singapore
city: Taipei City
country: Taiwan
facility: Taipei Medical University Hospital
state: Taipei
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung MemorialHospital
city: Keelung
country: Taiwan
facility: Chang Gung Memorial Hospital, Keelung
city: Tainan city
country: Taiwan
facility: Liuying Chi MeiMedical Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital
city: Manchester
country: United Kingdom
facility: The Christie Hospital NHS Foundation Trust
Study officials:
affiliation: MacroGenics
name: Stephen L. Eck, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Catenacci DV, Rosales M, Chung HC, H Yoon H, Shen L, Moehler M, Kang YK. MAHOGANY: margetuximab combination in HER2+ unresectable/metastatic gastric/gastroesophageal junction adenocarcinoma. Future Oncol. 2021 Apr;17(10):1155-1164. doi: 10.2217/fon-2020-1007. Epub 2020 Dec 2.