Combination Therapy for Gastric Cancer

(MAHOGANY Trial)

No longer recruiting at 89 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for individuals with HER2-positive gastric cancer or gastroesophageal junction cancer. It tests various drug combinations, including margetuximab, retifanlimab (Zynyz), tebotelimab, and chemotherapy (cytotoxic therapy), to determine which are most effective. Participants in Part A receive margetuximab and retifanlimab, while Part B compares four different combinations of these drugs with chemotherapy. Those diagnosed with HER2-positive gastric cancer who have not previously undergone chemotherapy may be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of margetuximab and retifanlimab is generally well-tolerated by patients with stomach or gastroesophageal junction cancer. Studies indicate that this treatment, especially when used without chemotherapy, is usually manageable for patients. However, severe side effects have been reported in 57% to 81% of cases when combined with other drugs like chemotherapy.

For the combination of margetuximab and tebotelimab, ongoing research has shown a promising safety profile so far. Margetuximab, when used with chemotherapy, has also been studied and is generally considered safe, although some patients experience severe side effects related to the treatment.

Overall, these treatments have undergone extensive testing, providing substantial safety information. Since this is still in the trial phase, researchers will continue to monitor and report to ensure patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for gastric cancer because they offer potential advancements over the standard of care, which typically involves chemotherapy with drugs like fluorouracil, oxaliplatin, and capecitabine combined with trastuzumab for HER2-positive cancers. The investigational treatments in this trial feature margetuximab, a novel HER2-targeted antibody that might improve immune system engagement compared to trastuzumab. Retifanlimab and tebotelimab are immune checkpoint inhibitors that could potentially enhance the body's immune response against cancer cells. By combining these innovative agents with or without chemotherapy, these treatments aim to provide more effective options for patients with gastric cancer.

What evidence suggests that this trial's treatments could be effective for gastric cancer?

In this trial, participants will join different treatment arms to evaluate the effectiveness of various combination therapies for HER2-positive gastric or gastroesophageal junction cancer. Previous studies have shown that margetuximab is more effective than trastuzumab in treating HER2-positive gastric cancer. One arm of this trial will test margetuximab combined with retifanlimab, a drug that helps the immune system fight cancer, which has shown promising results in improving response rates in similar cancers. Another arm will evaluate margetuximab with tebotelimab, another immune-boosting drug, which research suggests can help the immune system attack cancer cells. Additionally, some arms will test margetuximab combined with chemotherapy, which has demonstrated a stronger ability to kill cancer cells compared to trastuzumab. These findings suggest that the combination therapies tested in this trial could potentially offer better outcomes for patients. ^{1 2 6 7 8}

Who Is on the Research Team?

Stephen L. Eck, MD, PhD

Principal Investigator

MacroGenics

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04082364

NCT04082364 | Combination Margetuximab, Retifanlimab ...

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) ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9588876/

Margetuximab with retifanlimab as first-line therapy in HER2+ ...

According to recent studies on triple combination with anti-PD-1, trastuzumab, and chemotherapy, TRAEs of grade 3-5 were reported in 57%-81% of ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11083522/

Recent Progress in Treatment for HER2-Positive Advanced ...

Margetuximab demonstrated significantly higher cytotoxicity than trastuzumab. ORR was 12% and mPFS was 14 weeks; nevertheless, the participants ...

4.

ir.macrogenics.com

ir.macrogenics.com/news-releases/news-release-details/macrogenics-announces-clinical-results-cohort-part-1-phase-23

Press Release

Both GC and GEJ cancer are often diagnosed at an advanced stage and therefore have very poor prognosis, with a 5-year survival of 5-20%. Chemotherapy is the ...

5.

tandfonline.com

tandfonline.com/doi/full/10.2217/fon-2020-1007

MAHOGANY: Margetuximab Combination in HER2+ ...

Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer ( ...

6.

ir.macrogenics.com

ir.macrogenics.com/news-releases/news-release-details/phase-1b2-study-margetuximab-combination-pembrolizumab-presented

Phase 1b/2 Study of Margetuximab in Combination with ...

The Overall Response Rate (ORR) was higher in patients with gastric vs. GEJ cancer (32% vs. 4%). ORR across all patients in the study was 18% (six confirmed and ...

7.

thelancet.com

thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30326-0/abstract

Margetuximab plus pembrolizumab in patients with ...

Median follow-up was 19·9 months (IQR 10·7–23·1). The combination therapy showed acceptable safety and tolerability; there were no dose-limiting ...

8.

clin.larvol.com

clin.larvol.com/trial-detail/NCT04082364

Combination Margetuximab, Retifanlimab, Tebotelimab, ...

“Margetuximab: Phase 2/3 MAHOGANY study in advanced gastric and gastroesophageal junction cancer. The Company plans to report interim safety and efficacy data ...