Phase 3
N=82
Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer
Gastric Cancer · Gastroesophageal Junction Cancer · HER2-positive Gastric Cancer
Bottom Line
View on ClinicalTrials.gov: NCT04082364 ↗Enrolled (actual)
82
Serious AEs
43.2%
Results posted
Apr 2025
Primary outcome: Primary: Number of Participants With Adverse Events of Margetuximab Plus Retifanlimab in Cohort A, as Assessed by CTCAE v5.0 — 47; 38; 25; 12 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- margetuximab (Biological); Retifanlimab (Biological); Tebotelimab (Biological); Trastuzumab (Biological); Chemotherapy (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- MacroGenics
- Primary completion
- Jan 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events of Margetuximab Plus Retifanlimab in Cohort A, as Assessed by CTCAE v5.0 |
47; 38; 25; 12; 8 | — |
| PRIMARY Objective Response Rate (ORR) for Non-microsatellite Instability-high (Non-MSI-H) Participants (Cohort A) Using Investigator-assessed Radiology Reviews |
52.1 | — |
| SECONDARY Median Progression-free Survival Using Investigator-assessed Radiology Reviews in Cohort A |
9.8 | — |
| SECONDARY Median Duration of Response in Cohort A Using Investigator-assessed Radiology Reviews |
16.1 | — |
| SECONDARY Disease Control Rate |
83.3; 87.5; 100; 100; 100 | — |
| SECONDARY ORR for Cohort B |
62.5; 88.9; 83.3; 90.0 | — |
| SECONDARY Number of Participants Who Have Antidrug Antibodies (ADA) to Margetuximab |
40; 8; 5; 10; 5; 1 | — |
| SECONDARY Number of Participants Who Have ADA to Retifanlimab |
43; 9; 3; 0; 1; 0 | — |
| SECONDARY Number of Participants Who Have ADA to Tebotelimab |
1; 4; 1 | — |
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
- 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 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
Data sourced from ClinicalTrials.gov (NCT04082364). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.