Clinical trial

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

Name

CP-MGAH22-06

Description

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.

Trial arms

Trial start

2019-09-30

Estimated PCD

2024-03-01

Trial end

2024-03-01

Status

Active (not recruiting)

Phase

Early phase I

Treatment

margetuximab

margetuximab: Fc-modified anti-HER2 monoclonal antibody: 15 mg/kg IV, Day1 of each 3-week cycle

Arms:

Chemotherapy-free arm, Margetuximab and chemotherapy arm, Margetuximab, retifanlimab, and chemotherapy arm, Margetuximab, tebotelimab and chemotherapy arm

Other names:

MGAH22, Margenza®

Retifanlimab

Retifanlimab: anti-PD-1 checkpoint inhibitor 375 mg IV, Day 1 of each 3-week cycle.

Arms:

Chemotherapy-free arm, Margetuximab, retifanlimab, and chemotherapy arm

Other names:

MGA012, INCMGA00012

Tebotelimab

Tebotelimab: anti PD-1, anti-LAG3 bispecific DART (R) molecule 600 mg IV, Day 1 of each 3-week cycle.

Arms:

Margetuximab, tebotelimab and chemotherapy arm

Other names:

MGD013

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

Arms:

Trastuzumab and chemotherapy arm

Other names:

Herceptin

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.

Arms:

Margetuximab and chemotherapy arm, Margetuximab, retifanlimab, and chemotherapy arm, Margetuximab, tebotelimab and chemotherapy arm, Trastuzumab and chemotherapy arm

Size

Primary endpoint

Incidence of Adverse Events of margetuximab plus retifanlimab as assessed by CTCAE v5.0

Throughout the study up to 24 months

Objective response rate (ORR) for non-microsatellite instability-high (non-MSI-H) patients (Cohort A)

Throughout the study up to 24 months

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 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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2', 'PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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. Cohort B Part 2 is a randomized, 2-arm segment to evaluate margetuximab plus the selected checkpoint inhibitor from Part 1, plus chemotherapy vs. trastuzumab plus chemotherapy.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 82, 'type': 'ACTUAL'}}

Updated at

2023-12-26

1 organization

3 products

1 drug

3 indications

Organization

MacroGenics

Product

margetuximab

Indication

Stomach Cancer