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New treatment option for Locally Advanced Gastric Adenocarcinoma
Official title Zimberelimab Anti-PD1 +/- Domvanalimab in Resectable Mmrd Gastric Cancer
ClinicalTrials.gov ID: NCT06250036
What this study is testing
What is Single agent zimberelimab?
Single agent zimberelimab is an investigational medicine, being studied as a potential treatment for locally advanced gastric adenocarcinoma.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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)
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join 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...
- Polymerase chain reaction (PCR) amplification of microsatellite sequences
You likely can't join 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...
- Treatment with systemic immunosuppressive medications, including but not limited to: corticosteroids (dose of \> 10mg/day prednisone equivalent)...
- 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...
See the full eligibility criteria
Who can join
- 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...
- 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
What rules you out
- 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...
- Treatment with systemic immunosuppressive medications, including but not limited to: corticosteroids (dose of \> 10mg/day prednisone equivalent) cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumour...
- 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...
- 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...
- 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...
- 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
- Cerebrovascular disease (including transient ischaemic attacks (TIA) and strokes) within the 6 months prior to Cycle 1 Day 1
- Cardiovascular diseases as follows:
- Myocardial infarction within the previous year
- Serious cardiac arrhythmia requiring medication (for example, ventricular tachycardia, supraventricular tachycardia or atrial fibrillation with a resting heart rate \> 110bpm)
- Unstable angina
- Congestive cardiac failure (New York Heart Association Classification Class III or IV), EF \<50%
- Active infection requiring systemic therapy, non-healing wound, ulcer or bone fracture requiring therapy
- Major surgery, major trauma within 28 days prior to registration (not including staging laparoscopy)
- Current signs or symptoms of any other severe progressive or uncontrolled hepatic, haematologic, gastrointestinal, endocrine, respiratory or cardiac disease other than directly related to gastric/GOJ adenocarcinoma...
- Other severe acute or chronic medical conditions or psychiatric conditions including recent (within the past year) active suicidal ideation or behaviour
- Active/ uncontrolled Hepatitis A, B or C infection, for hepatitis B known positive HBV surface antigen (HBsAg) result, patients with past or resolved HBV infection (defined as the presence of hepatitis B core antibody...
- Uncontrolled human immunodeficiency virus (HIV) infection
- If known HIV diagnosis and well controlled on anti-retrovirals (CD4 count ≥350cells/ul and undetectable viral load) patient is eligible, ensure HIV team involvement for management and monitoring whilst on treatment
- Use of live attenuated vaccine within 28 days of initiation of study therapy, or anticipation that a live attenuated vaccine will be required during the study
- Pregnancy must be excluded with a negative serum pregnancy test, within 3 days before initiation of therapy, if the risk of conception exists. Sexually active female patients must be surgically sterile or be...
- Lactation-breast-feeding is contraindicated and must be discontinued for the duration of the study period and for the required duration of the contraception use after the last dose of the study drug.
- Any patient specific factors which are likely to interfere with compliance of trial specific procedures or treatment, including any medical or psychiatric conditions that in the investigator's or sponsor's opinion poses...
The study team makes the final eligibility decision.
Where it's taking place
- Cambridge, Cambridgeshire, United Kingdom
- Exeter, Devon, United Kingdom
- Dundee, Dundee, United Kingdom
- Canterbury, Kent, United Kingdom
- London, London, United Kingdom
- Leeds, Yorkshire, United Kingdom
- London, United Kingdom
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Cambridge, Cambridgeshire, United Kingdom; Exeter, Devon, United Kingdom; Dundee, Dundee, United Kingdom; Canterbury, Kent, United Kingdom; London, London, United Kingdom; Leeds, Yorkshire, United Kingdom and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.
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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.