0

Zimberelimab + Domvanalimab for Stomach and Esophageal Cancer

SJ
Overseen BySamuel J. Klempner, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the combination of two immune therapy drugs, domvanalimab and zimberelimab, alongside standard chemotherapy to determine their safety and effectiveness in treating certain stomach and esophageal cancers. Participants will receive these treatments for up to 4 months before surgery, followed by additional immune therapy for up to 8 months post-surgery. The trial seeks individuals who have not yet received treatment for their stomach or gastroesophageal junction cancer and have been informed that their cancer is operable. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer therapy.

Will I have to stop taking my current medications?

The trial requires participants to be treatment naïve, meaning you cannot have received prior treatments for your cancer. If you are on medications for other conditions, the protocol does not specify if you need to stop them, but you should discuss this with the trial team.

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

Research has shown that the combination of domvanalimab and zimberelimab with chemotherapy has been well-studied in patients with advanced stomach and gastroesophageal cancers. Studies have found that most people can tolerate this combination without serious problems. Previous trials reported no unexpected safety issues. The overall response rate (ORR), which measures how well tumors shrink or disappear, was about 59%. Patients lived for a median of 26.7 months, which is promising.

These findings suggest the treatment is relatively safe, especially since no new safety concerns have emerged. However, like any medical treatment, side effects can occur. Discuss any concerns with a healthcare provider before joining a trial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about zimberelimab and domvanalimab for stomach and esophageal cancer because these treatments work by harnessing the immune system in a unique way. Unlike traditional chemotherapy, which directly targets cancer cells, zimberelimab and domvanalimab are monoclonal antibodies that help the immune system recognize and attack cancer cells more effectively. This approach targets specific proteins that usually help cancer cells evade the immune system, potentially leading to more precise and less toxic treatment. As a result, these therapies could offer a new hope for patients by improving outcomes and reducing side effects compared to standard chemotherapy options like fluorouracil, oxaliplatin, leucovorin, and docetaxel.

What evidence suggests that zimberelimab and domvanalimab might be effective treatments for stomach and esophageal cancer?

Research shows that the combination of domvanalimab and zimberelimab holds promise for treating stomach and esophageal cancers. In earlier studies, this combination achieved a 59% success rate in shrinking tumors in patients with advanced gastroesophageal cancer. Patients receiving this treatment lived for a median of 26.7 months, and the median time before the cancer worsened was 12.9 months. In this trial, participants will receive domvanalimab and zimberelimab along with neoadjuvant FLOT therapy. These early results suggest that the treatment can effectively slow cancer progression and extend patient survival.12678

Who Is on the Research Team?

SJ

Samuel J. Klempner, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for patients with operable esophageal, stomach, or gastroesophageal junction cancer. Participants will undergo standard chemotherapy combined with two immune therapy drugs before and after surgery. The study requires a commitment of up to 5 years including treatment and follow-up.

Inclusion Criteria

My cancer is a type of stomach or junction cancer confirmed by tissue analysis.
My organs and bone marrow are functioning well.
I have not received any treatment for my condition.
See 9 more

Exclusion Criteria

I am not currently taking any experimental drugs or other cancer treatments.
I haven't taken steroids or immunosuppressants in the last 14 days.
Participants with uncontrolled intercurrent illness that would interfere with ability to participate
See 16 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive up to 8 cycles of domvanalimab, zimberelimab, and FLOT chemotherapy before surgery

16 weeks
8 visits (in-person, bi-weekly)

Surgery and Recovery

Participants undergo surgical resection and recover for 4-12 weeks

4-12 weeks

Adjuvant Treatment

Participants receive domvanalimab and zimberelimab for up to 8 cycles post-surgery

32 weeks
8 visits (in-person, monthly)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

  • Domvanalimab
  • Zimberelimab

Trial Overview

The effectiveness and safety of combining domvanalimab and zimberelimab with FLOT chemotherapy are being tested in this study. Patients receive these treatments for four months pre-surgery, then continue the immune therapies for eight more months post-surgery.

How Is the Trial Designed?

1

Treatment groups

Experimental Treatment

Group I: Zimberelimab + Domvanalimab +neoadjuvant FLOTExperimental Treatment3 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials
3,066
Recruited
13,430,000+

Arcus Biosciences, Inc.

Industry Sponsor

Trials
44
Recruited
7,500+

Gateway for Cancer Research

Collaborator

Trials
47
Recruited
2,500+

Citations

Domvanalimab and zimberelimab in advanced gastric ...

After a median study follow-up of 26.4 months, outcomes were encouraging, with an ORR of 59%, median DOR of 12.4 months, median PFS of 12.9 ...

Anti-TIGIT Domvanalimab Plus Anti-PD-1 Zimberelimab ...

Anti-TIGIT Domvanalimab Plus Anti-PD-1 Zimberelimab and Chemotherapy Showed 26.7 Months of Median Overall Survival as First-Line Treatment of ...

Domvanalimab Combo Shows Enriched First-Line Efficacy ...

The combination of domvanalimab and zimberelimab showed a 59% objective response rate in advanced HER2-negative gastroesophageal cancer patients ...

EDGE Gastric Study at ESMO 2025: Domvanalimab ...

At 26 months of follow-up, dual PD-1/TIGIT blockade with domvanalimab and zimberelimab plus FOLFOX achieved prolonged survival outcomes—with a ...

EDGE-Gastric Trial: Breaking Down Data for ...

They outline key efficacy signals, including durability of response, and progression-free survival trends, while also commenting on the safety ...

Zimberelimab + Domvanalimab in Gastroesophageal ...

This is a single-center, phase II study evaluating the efficacy, activity and safety of domvanalimab and zimberelimab with standard chemotherapy ...

Phase 3 STAR-221 Study of First-Line Domvanalimab ...

The confirmed ORR per RECIST 1.1 criteria was 59% (90% CI, 45%-72%). No unexpected safety signals were observed at the time of data cutoff, and ...

EDGE-Gastric Arm A1: Phase 2 study of domvanalimab ...

There was an even distribution of pts accrued in Asia vs. rest of world and 63% of pts had gastric cancer. Median time on treatment was 23 weeks (1 to 40), 31 ...