Zimberelimab Anti-PD1 +/- Domvanalimab in Resectable Mmrd Gastric Cancer

Recruiting now · Phase 2

Conditions studied: Locally Advanced Gastric Adenocarcinoma, MSI-H/dMMR Gastric Cancer, MSI-H/dMMR Gastroesophageal-junction Cancer

In brief

A phase II study of peri-operative anti-PD1 (Zimberelimab) +/- anti-TIGIT (Domvanalimab) in resectable mismatch repair deficient (MMRd)/ high micro-satellite instability (MSI-H) gastric/gastro-oesophageal junctional (GOJ) adenocarcinoma (AC)

Key facts

Study ID

NCT06250036

Run by

Royal Marsden NHS Foundation Trust

People needed

50

Starts

2025-02-20

Expected to finish

2031-09-01

Last updated by the study team

2025-08-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age: ≥18 years
• Histologically confirmed gastric or gastro-oesophageal junctional (GOJ) adenocarcinoma (inclusive of Siewert-stein classification type I-III (62))
• MMRd/MSI-H. There are three different methods validated for detection (63) :
• Immunohistochemistry (IHC) staining for expression of MMR proteins (MLH1, MSH2, PMS2 and MSH6), MMRd defined as loss of function or one or more of these proteins.
• Polymerase chain reaction (PCR) amplification of microsatellite sequences
• Next-generation sequencing (NGS) for detection of MSI
• Stage II-IIIB: TNM T2-T4, N0-N3, M0
• Absence of distant metastatic disease on CT scan + PET CT + staging laparoscopy prior to study entry.
• MDT determined suitable for surgery and MDT believes an R0 resection is achievable after neo-adjuvant therapy (resectable disease)
• No prior anti-cancer therapy for gastric / GOJ adenocarcinoma
• ECOG performance status 0-2
• Laboratory parameters
• Adequate haematologic and end-organ function defined by the following laboratory test results: Haematology: Absolute neutrophil count > 1.5 x 109/L Platelets > 100 x 109/L Haemoglobin > 90 x 109/L (can be post-transfusion) Biochemistry: Serum Creatinine Clearance >50ml/min (calculated using Cockcroft-Gault formula Appendix X)
• Liver function: Bilirubin within normal limits ALT/AST ≤2.5x ULN
• Coagulation profile (for patients not receiving therapeutic anticoagulation):
• International Normalised Ratio (INR) < 1.5 Activated Prothrombin Time (APTT) < 1.5xULN
• Before patient registration/randomisation, written informed consent must be given according to ICH/GCP, and national/local regulations
• Patient is fit to undergo all protocol investigations and receive all protocol treatment based on the assessment in the surgical / oncology clinic
• Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrolment
• Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans

You may not qualify if…

• Patients are not eligible for the trial if any of the exclusion criteria below are met:
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3CTCAE v5.0, any history of anaphylaxis
• Any prior treatment with cancer immunotherapy including anti-PD-1, anti-TIGIT, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Treatment with systemic immunosuppressive medications, including but not limited to: corticosteroids (dose of > 10mg/day prednisone equivalent) cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour necrosis factor [TNF] agents) within 2 weeks prior to Cycle 1 Day 1
• Prior malignancy active within the previous 2 years except for:
• locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix
• localised prostate cancer
• breast cancer diagnosed >2 years ago, now on adjuvant endocrine therapy (no known active disease)
• Patients recommended to have radiotherapy as part of routine management for their gastric/GOJ AC are ineligible
• QTc ≥480 msec using Fredericia QT correction formula
• Metastatic disease on imaging or staging laparoscopy - visualisation of peritoneal disease on staging laparoscopy is an exclusionPrior organ transplantation, including allogeneic stem-cell transplantation
• Any active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) or is expected to deteriorate when receiving immunotherapy, with the following exceptions:
• Patients with autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible
• Patients only receiving hormone replacement therapy e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy (doses ≤10mg - or equivalent - of prednisolone per day) for adrenal or pituitary insufficiency) are eligible
• Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only not requiring immunosuppressive treatment are eligible, providing they meet the following conditions
• Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
• Rash mush cover less than 10% of body surface area
• Disease is well controlled at baseline and only requiring low-potency topical steroids
• No acute exacerbations of underlying condition within the last 12 months
• Patients with controlled type 1 diabetes mellitus on a stable dose of insulin regimen are eligible
• Patients requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement
• Administration of steroids through a route known to result in minimal systemic exposure (topical, intranasal intra-ocular, or inhalation) are acceptable. Steroids as pre-medication for hypersensitivity reactions e.g., CT contrast are also acceptable
• History of inflammatory bowel disease with the following exception:
• Patients with a history of ulcerative colitis who have had a colectomy are eligible
• Patients with a history of interstitial lung disease or radiological evidence of pulmonary fibrosis

Where it is running

• Addenbrooke's Hospital — Cambridge, Cambridgeshire, United Kingdom (enrolling)
• Royal Devon University Healthcare Foundation Trust — Exeter, Devon, United Kingdom (enrolling)
• Ninewells hospital and Medical School — Dundee, Dundee, United Kingdom (enrolling)
• Kent & Canterbury Hospital — Canterbury, Kent, United Kingdom (enrolling)
• Guy's and St Thomas' NHS Foundation Trust — London, London, United Kingdom (enrolling)
• The Royal Marsden NHSFT — London, London, United Kingdom (enrolling)
• St James's University hospital — Leeds, Yorkshire, United Kingdom (enrolling)
• St Bartholomew's Hospital — London, United Kingdom (enrolling)
• University College London Hospital NHS Foundation Trust — London, United Kingdom (enrolling)

Full record on ClinicalTrials.gov

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