A Safety and Efficacy Study of Domvanalimab + Zimberelimab Combination Therapy in Participants With Advanced Upper Gastrointestinal Tract Malignancies


About this study

This Phase 2, open-label, parallel, 3-cohort, multicenter study will evaluate the safety and efficacy of various combinations of the anti-T-cell immunoglobulin and ITM domain (TIGIT) monoclonal antibody domvanalimab, the anti-programmed cell death protein 1 (PD-1) monoclonal antibody zimberelimab, and multiagent chemotherapy in the first--line setting, and of various combinations of domvanalimab, zimberelimab, the cluster of differentiation 73 (CD73) inhibitor quemliclustat, and chemotherapy in the second-line (2L) or greater setting in participants with locally advanced unresectable or metastatic gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

- Participants with histologically confirmed diagnosis of locally advanced unresectable
or metastatic gastric, GEJ, or esophageal adenocarcinoma with life expectancy ≥3
months as assessed by the Investigator

- Eastern cooperative oncology group (ECOG) Performance Score of 0-1

- At least one measurable target lesion per RECIST v1.1.

- Adequate organ and marrow function

- Able to provide an archival tumor sample that is representative of the cancer under
investigation and suitable for central PD-L1 testing

Exclusion Criteria:

- Participants with underlying medical conditions that, in the Investigator's or
Sponsor's opinion, will make the administration of investigational products hazardous

- Only for Cohort A: Known Human Epidermal Growth Factor Receptor 2 (HER-2) positive

- Known untreated, symptomatic, or actively progressing central nervous system (brain)
metastases. Participants with leptomeningeal metastases are excluded from enrollment.

- Discontinued use of prior immune checkpoint therapy due to immune related adverse
events; received prior treatment with an anti-TIGIT monoclonal antibody.

- History of trauma or major surgery within 28 days prior to enrollment.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 2/2/23. Questions regarding updates should be directed to the study team contact.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mohamad Sonbol, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Jason Starr, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


Publications are currently not available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions