Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer

Gastric Cancer Clinical Trial

— MAHOGANY  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04082364
• Other study ID #: CP-MGAH22-06
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: September 30, 2019
• Est. completion date: March 2024

Study information

• Verified date: December 2023
• Source: MacroGenics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 patients) will evaluate safety and efficacy of margetuximab plus retifanlimab. Part B has 2 subparts. Cohort B1 has 4 arms (50 patients/arm). Patients will be randomized to margetuximab plus retifanlimab plus chemotherapy, margetuximab plus tebotelimab, plus chemotherapy, margetuximab plus chemotherapy, or trastuzumab plus chemotherapy. The most effective combination with margetuximab from Cohort B1 will be used in Cohort B2. Cohort B2 has 2 arms (250 patients/arm). Patients will be randomized to margetuximab plus retifanlimab or tebotelimab plus chemotherapy, or to trastuzumab plus chemotherapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 82
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer
• Gastroesophageal Junction Cancer
• HER2-positive Gastric Cancer
• Stomach Neoplasms

Intervention

Biological:
• margetuximab
margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle
• Retifanlimab
Retifanlimab: anti-PD-1 checkpoint inhibitor 375 mg IV, Day 1 of each 3-week cycle.
• Tebotelimab
Tebotelimab: anti PD-1, anti-LAG3 bispecific DART (R) molecule 600 mg IV, Day 1 of each 3-week cycle.
• Trastuzumab
Anti-HER2 monoclonal antibody 8 mg/kg loading dose and then 6 mg/kg administered IV on Day 1 of each 3-week cycle

Other:
• Chemotherapy
Investigator choice of 1 of 2 chemotherapy regimens: XELOX or mFOLFOX6 Chemotherapy XELOX chemotherapy Capecitabine: 1000 mg/m2 as oral capsules twice a day Days 1-14 of each cycle, Oxaliplatin: 130 mg/m2 of Day 1 of each 3-week cycle as IV infusion mFOLFOX6 chemotherapy: Leucovorin: 400 mg/m2 every 2 weeks as IV infusion, 5-FU bolus: 400 mg/m2 every 2 weeks as IV infusion, 5-FU continuous infusion: 2400 mg/m2 every 2 weeks as a 46 hr infusion, Oxaliplatin: 85 mg/m2 every 2 weeks as IV infusion.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Jilin Cancer Hospital (Second People's Hospital Of Jilin Province)	Changchun
China	Fujian Medical University - Fujian Provincial Cancer Hospital (Fujian Provincial Tumor Hospital)	Fuzhou
China	SIR RUN RUN SHAW Hospital, Zhejiang University school of medicine	Hangzhou
China	Zhejiang Cancer Hospital	Hangzhou
China	Affiliated Tumor Hospital of Harbin Medical University- the 3rd Affiliated Hospital of Harbin	Harbin
China	Anhui Provincial Cancer Hospital	Hefei
China	The First Affiliated Hospital of Anhui Medical University	Hefei
China	Jinan Center Hospital	Jinan
China	Nanjing University Medical School; Nanjing Drug Tower	Nanjing
China	Zhongshan Hospital Fudan University	Shanghai
China	Liaoning cancer hospital	Shenyang
China	Hebei cancer hospital (The Fourth Affiliate)	Shijiazhuang
China	Wuhan Union Hospital	Wuhan
China	Henan Cancer Hospital	Zhengzhou
China	The First Affiliated Hospital of Zhengzhou University	Zhenzhou
Germany	Institute of Clinical Cancer Research Krankenhaus Nordwest (IKF)	Frankfurt
Germany	Haematologisch-Onkologische Praxis Eppendorf	Hamburg
Germany	Universitätsmedizin Mainz	Mainz
Germany	Kliniken Maria Hilf GmbH	Monchengladbach
Italy	Istituto Europeo Di Oncologia	Milan
Italy	Ospedale San Raffaele	Milan
Italy	Azienda Ospedaliero-Universitaria Pisana	Pisa
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang-Si
Korea, Republic of	CHA bundang	Gyeonggi-do
Korea, Republic of	Inje University Haeundae Paik Hospital	Haeundae
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro	Seoul
Korea, Republic of	Korea University, Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University College of Medicine (Severance Hospital)	Seoul
Korea, Republic of	Catholic University of Korea St. Vincent Hospital	Suwon
Poland	SPSK nr 1 in Lublin	Lublin
Poland	Centrum Medyczne MrukMed	Rzeszów
Singapore	National Cancer Center Singapore	Singapore
Singapore	National University Hospital (Cancer Institute) -Singapore	Singapore
Taiwan	Kaohsiung Chang Gung MemorialHospital	Kaohsiung
Taiwan	Chang Gung Memorial Hospital, Keelung	Keelung
Taiwan	Liuying Chi MeiMedical Hospital	Tainan city
Taiwan	National Taiwan University	Taipei
Taiwan	Taipei Medical University Hospital	Taipei City	Taipei
United Kingdom	Cambridge University Hospitals NHS Foundation Trust Addenbrooke's Hospital	Cambridge
United Kingdom	The Christie Hospital NHS Foundation Trust	Manchester
United States	The University of New Mexico Comprehensive Cancer Center	Albuquerque	New Mexico
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Chicago	Chicago	Illinois
United States	Henry Ford Health System	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center - Duarte	Duarte	California
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Florida Cancer Specialists South	Fort Myers	Florida
United States	Cancer & Hematology Centers of Western Michigan - Lemmen-Holton Cancer Pavilion	Grand Rapids	Michigan
United States	Kaiser Permanente	Honolulu	Hawaii
United States	Oncology Consultants	Houston	Texas
United States	Mayo Clinic - Jacksonville	Jacksonville	Florida
United States	Nebraska Heme Onc	Lincoln	Nebraska
United States	Norris Comprehensive Cancer Center (USC)	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	Ocala Oncology Center PL DBA Florida Cancer Affiliates - Ocala	Ocala	Florida
United States	Stephenson Cancer Center at OUHSC	Oklahoma City	Oklahoma
United States	Mayo Clinic - Rochester	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Florida Cancer Specialists North	Saint Petersburg	Florida
United States	Salinas Memorial	Salinas	California
United States	Utah Cancer Specialists	Salt Lake City	Utah
United States	UCLA School of Medicine	Santa Monica	California
United States	Mayo Clinic - Scottsdale	Scottsdale	Arizona
United States	Swedish Cancer Institute	Seattle	Washington
United States	Edward H. Kaplan MD & Associates	Skokie	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
MacroGenics	Zai Lab (Shanghai) Co., Ltd.

Countries where clinical trial is conducted

United States,  China,  Germany,  Italy,  Korea, Republic of,  Poland,  Singapore,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events of margetuximab plus retifanlimab as assessed by CTCAE v5.0	Evaluation of adverse events and serious adverse events (Cohort A)	Throughout the study up to 24 months
Primary	Objective response rate (ORR) for non-microsatellite instability-high (non-MSI-H) patients (Cohort A)	Proportion of non MSI-H patients with best overall response of complete response (CR) plus partial response (PR) per RECIST 1.1 (Cohorts A )	Throughout the study up to 24 months
Secondary	Progression-free survival	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)	Up to 3 years
Secondary	Duration of response	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)	Up to 3 years
Secondary	Disease control rate	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)	Up to 3 years
Secondary	ORR for Cohort B	Proportion of non-MSI-high patients iwth best overall response of CR plus PR per RECIST 1.1	Throughout study participation, up to 24 months.
Secondary	Number of patients who have antidrug antibodies (ADA) to margetuximab		Throughout study participation, up to 24 months.
Secondary	Number of patients who have ADA to retifanlimab		Throughout study participation, up to 24 months.
Secondary	Number of patients who have ADA to tebotelimab		Throughout study participation, up to 24 months.