Metastatic or Locally Advanced, Treatment-naïve, HER2-Positive Gastric or Gastroesophageal Junction Cancer MedDRA version: 23.0 Level: PT Classification code 10066896 Term: HER2 positive gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version:
Conditions
Interventions
Product Name: Margetuximab
Product Code: MGAH22
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Margetuximab
CAS Number: 1350624-75-7
Current Sponsor code: MGAH22
Other
Sponsors
MacroGenics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of previously untreated locally advanced unresectable or metastatic HER2+ GC or GEJ adenocarcinoma - 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. -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. -Patients receiving perioperative anti-HER2 therapy require testing of HER2 status for eligibility. 2. Availability of formalin-fixed, paraffin-embedded tumor specimen, unstained slides or contemporaneous biopsy for tumor target testing 3. Eastern Cooperative Oncology Group performance status of 0 or 1, verified within 3 days of Day 1 4. Life expectancy = 6 months 5. At least one radiographically measurable target lesion 6. Acceptable laboratory parameters and adequate organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 460 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: 1. Other malignancy that is progressing or required treatment within the past 5 years, with certain exceptions -Patients with known MSI-H status 2. History of allogeneic stem cell or tissue/solid organ transplant 3. Central nervous system metastases 4. Clinically significant cardiovascular disease, gastrointestinal disorders, pulmonary compromise 5. Prior neoadjuvant or adjuvant treatment with immunotherapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Cohort A: To evaluate the safety and tolerability of margetuximab + INCMGA00012 in patients with untreated locally advanced or metastatic GC or gastroesophageal junction (GEJ) cancer that is HER2 IHC 3+ and PD-L1+ by IHC staining. To evaluate the ORR of margetuximab plus INCMGA00012 for non-MSI-H patients in the response evaluable population (REP) using independent and Investigator-assessed radiology reviews. Cohort B, Part 1: To select the best margetuximab, chemotherapy and CPI-containing combination regimen for further evaluation in Part 2, based on evaluation of safety and ORR in the primary response evaluable population (PREP) of patients with GC or GEJ cancer, irrespective of PD-L1 status. Cohort B, Part 2: To compare the OS of patients treated with the margetuximab, chemotherapy and CPI-containing arm selected from Cohort B Part 1 to that of patients treated with trastuzumab plus chemotherapy (control arm) in the primary efficacy population.;Secondary Objective: Cohort A: To determine duration of response (DoR), disease control rate (DCR), progression-free survival (PFS) using independent and Investigator-assessed radiology review, and OS for non-MSI-H patients. Cohort B, Part 1: To evaluate PFS, OS, DoR, and DCR of each treatment arm. To evaluate the ORR, DoR, DCR, PFS, and OS in the double-positive (HER2 3+ and PD-L1+) and non-MSI-H population in the margetuximab and chemotherapy arm Cohort B Part 2: To evaluate PFS, DoR, ORR and DCR of each treatment arm. To evaluate OS in the intent-to-treat (ITT), and non-PEP populations. To evaluate the ORR, PFS, DoR, DCR and OS in the double-positive (HER2 3+ and PD-L1+) and non-MSI-H population in the margetuximab and CPI-containing arm. -Please refer to protocol for further details. ;Primary end point(s): 1) Incidence of Adverse Events of margetuximab plus INCMGA00012 as assessed by CTCAE v5.0 -Evaluation of adverse events and serious adverse events (Cohort A) 2) Objective response rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) 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 and B) 2) 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 and B) 3) 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) 4) Patient reported quality of life -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. ;Timepoint(s) of evaluation of this end point: 1) Time Frame: Up to 3 years 2) Time Frame: Up to 3 years 3) Time Frame: Up to 3 years 4) Time Frame: Up to 3 years | — |
Countries
China, Germany, Italy, Korea, Republic of, Netherlands, Poland, Singapore, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Project Management
MacroGenics, Inc.
Outcome results
None listed