Combination Therapy for Gastric Cancer

(MAHOGANY Trial)

Recruiting at 72 trial locations

Overseen By Aisha Wynter-Horton

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: MacroGenics

Must not be taking: Immunotherapy

Disqualifiers: Other malignancy, Transplant history, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 11 months

82 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

Stephen L. Eck, MD, PhD

Principal Investigator

MacroGenics

Eligibility Criteria

This trial is for adults with untreated advanced HER2+ gastric or gastroesophageal junction cancer. They should have a good performance status, measurable tumor lesions, and no central nervous system metastases. Prior systemic treatment is okay if there's been a disease-free period of at least 6 months.

Inclusion Criteria

My cancer is advanced, cannot be surgically removed, and is HER2 positive.

Life expectancy ≥ 6 months

I had treatment before or after surgery and have been disease-free for at least 6 months.

Exclusion Criteria

My cancer is MSI-H.

My cancer has spread to my brain.

I have received immunotherapy before surgery or alongside other treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive margetuximab in combination with retifanlimab and chemotherapy or tebotelimab and chemotherapy

11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Chemotherapy
• Margetuximab
• Retifanlimab
• Tebotelimab
• Trastuzumab

Trial Overview The study tests combinations of margetuximab with retifanlimab or tebotelimab plus chemotherapy against trastuzumab with chemo in two parts: initial safety/efficacy assessment (Part A) and randomized comparison to find the best combo (Parts B1 & B2).

Participant Groups

Group I: Margetuximab, tebotelimab and chemotherapy arm Experimental Treatment 3 Interventions

margetuximab plus tebotelimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)

Group II: Margetuximab, retifanlimab, and chemotherapy arm Experimental Treatment 3 Interventions

margetuximab plus retifanlimab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)

Group III: Margetuximab and chemotherapy arm Experimental Treatment 2 Interventions

margetuximab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)

Group IV: Chemotherapy-free arm Experimental Treatment 2 Interventions

margetuximab plus retifanlimab

Group V: Trastuzumab and chemotherapy arm Active Control 2 Interventions

Trastuzumab plus investigator choice of chemotherapy options. Chemotherapy options: capecitabine and oxaliplatin (XELOX) or modified 5-FU, leucovorin, and oxaliplatin regimen 6 (mFOLFOX-6)

Chemotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in United States as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Canada as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Japan as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in China as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Approved in Switzerland as Chemotherapy for:

• Breast cancer
• Metastatic breast cancer
• Various other cancers

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Zai Lab (Shanghai) Co., Ltd.

Industry Sponsor

Trials

30

Recruited

3,800+