An official website of the United States government
Intratumoral 2141-V11, Nivolumab and Fluorouracil for the Treatment of Locally Advanced Unresectable or Metastatic Esophageal, Gastric or Gastroesophageal Junction Adenocarcinoma
Trial Status: active
This phase Ib/II trial tests the safety, side effects and effect of 2141-V11 given intratumorally, in combination with nivolumab and fluorouracil for the treatment of esophageal, gastric or gastroesophageal junction adenocarcinoma that has spread to nearby tissue or lymph nodes and cannot be removed by surgery (locally advanced unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). 2141-V11 is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. 2141-V11 is a type of drug called a monoclonal antibody. Monoclonal antibodies are proteins made in a laboratory that are designed to find and attach to specific targets in the body. 2141-V11 targets a protein called CD40, which is found on immune cells called antigen-presenting cells (APCs). APCs are cells in the immune system that help activate other immune cells, including T cells, which find and kill tumor cells. When 2141-V11 binds to CD40 on these immune cells, it activates them, which may help the immune system recognize and attack tumor cells. To reduce the risk of side effects, 2141-V11 is injected directly into the tumor (intratumoral) rather than given through a vein. Fluorouracil is in a class of medications called antimetabolites. It works by stopping or slowing the growth of tumor cells. Giving 2141-V11 intratumorally along with nivolumab and fluorouracil may be safe, tolerable and/or effective in treating patients with locally advanced unresectable or metastatic esophageal, gastric and gastroesophageal junction adenocarcinoma.
Inclusion Criteria
Histologically confirmed esophageal, gastric, or gastroesophageal junction adenocarcinoma
Locally advanced unresectable or metastatic disease at diagnosis
On first line systemic therapy including fluoropyrimidine + anti-PD-1 therapy for advanced GEA (e.g. fluorouracil/leucovorin calcium/oxaliplatin [FOLFOX] + nivolumab) for a minimum of 3 months and no more than 9 months.
* Platinum chemotherapy included in first line regimen has been discontinued or will be discontinued ≥ 2 weeks prior to first planned dose of 2141-V11
* Patients in the safety lead-in cohort must be on 5-FU
Primary esophageal, gastric, or gastroesophageal junction tumor intact and visible at time of enrollment (within 1 month of 2141-V11 treatment initiation) on endoscopy
Evaluable disease at time of 2141-V11 treatment initiation as defined per RECIST v 1.1
Able to undergo endoscopy
Age 18 years or older
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Absolute neutrophil count ≥ 1000/mcL
Platelets ≥ 90,000/mcL
Hemoglobin ≥ 8 g/dL
Serum creatinine ≤ 1.5 X upper limit of normal (ULN)
Serum total bilirubin ≤ 1.5X ULN OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 X ULN, except patients with Gilbert's disease (≤ 3 X ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 X ULN
Albumin ≥ 3 mg/dL
Exclusion Criteria
Mismatch repair deficient (dMMR) disease by immunohistochemistry (IHC) or microsatellite instability (MSI-H) by next-generation sequencing
Known HER2-positive disease (IHC 3+ or IHC 2+ and amplification via fluorescence in situ hybridization)
Prior radiation therapy to primary esophageal, gastric, or gastroesophageal junction tumor
Anti-PD-1 therapy in ongoing regimen has been discontinued for any reason
Disease progression on frontline therapy
Patients with active autoimmune disease requiring ongoing systemic steroids or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment
Ongoing systemic steroids or receipt of systemic steroid therapy exceeding prednisone 10 mg/day or equivalent within 7 days before first dose, except physiologic replacement or short-course premedication (e.g. as antiemetics or CT scan contrast premedication), or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment. Use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
Patients with active infection on parenteral antibiotics
Patients with history of grade 3 or higher immune related adverse events to anti-PD-1 therapy may only be enrolled with the permission of the study principal investigator (PI)
Prior treatment before ongoing regimen for any reason with PD-1, PD-L1, or CTLA-4 inhibitors
Currently participating in a therapeutic study and receiving study therapy or has participated in a therapeutic study within 4 weeks of the first dose of treatment. Radiographic protocols including protocols with experimental tracers are not considered therapeutic studies and are exempt
Known active central nervous system metastases and/or leptomeningeal disease
HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) testing do not need to be performed as part of the study. For patients with known HIV, HBV, and/or HCV infection:
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Unwilling to give written, informed consent, unwilling to participate, or unable to comply with the protocol for the duration of the study
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07818018.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Samuel L Cytryn
Phone: 646-888-4896
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Samuel L Cytryn
Phone: 646-888-4896
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Samuel L Cytryn
Phone: 646-888-4896
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Samuel L Cytryn
Phone: 646-888-4896
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Samuel L Cytryn
Phone: 646-888-4896
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Samuel L Cytryn
Phone: 646-888-4896
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Samuel L Cytryn
Phone: 646-888-4896
PRIMARY OBJECTIVES:
I. Evaluate the safety of intratumoral Fc-engineered anti-CD40 agonist antibody 2141-V11 (2141-V11), administered during ongoing anti-PD-1 ± fluoropyrimidine (5-fluorouracil [5-FU]) therapy in patients with advanced esophageal, gastric, or gastroesophageal junction adenocarcinoma (GEA). (Safety Lead-In Cohort)
II. Assess the efficacy of 2141-V11 added to ongoing anti-PD-1 ± fluoropyrimidine therapy, as measured by 6-month progression free survival (PFS) from time of 2141-V11 initiation. (Expansion Cohort)
SECONDARY OBJECTIVES:
I. Determine additional measures of efficacy, including disease control rate (DCR), duration of response (DOR), PFS, overall survival (OS), objective response rate (ORR), duration of disease control, and reduction in injected and non-injected lesions.
II. Assess the feasibility of intratumoral 2141-V11 delivered via endoscopic injection.
EXPLORATORY OBJECTIVES:
I. Evaluate the local anti-tumor immune response, specifically focusing on immune infiltration and organization in injected lesions.
II. Measure the abscopal effect of 2141-V11 to cause anti-tumor immune organization in non-injected lesions.
III. Evaluate the impact of intratumoral 2141-V11 on the systemic anti-tumor immune response, specifically the clonal T cell and B cell response.
IV. Bank fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissue biopsies as well as blood at screening, and throughout treatment for additional future correlative analyses.
OUTLINE: This is a phase I study of 2141-V11 given combination with fixed dose nivolumab and fluorouracil followed by a phase II dose expansion study.
Patients receive 2141-V11 via intratumoral injection during endoscopy on day 1 of each cycle. Cycles for 2141-V11 repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. In the event of progression in the primary tumor after a minimum of 6 months since the last dose of 2141-V11, patients may receive up to 4 additional cycles of 2141-V11. Patients also receive nivolumab intravenously (IV) over 15-30 minutes every 2 or 4 weeks at the discretion of the treating investigator, and fluorouracil IV continuously over 48 hours every 2 weeks in the absence of disease progression or unacceptable toxicity. Dates of planned administration of 2141-V11 (e.g., day 1 of cycles 1-4) do not need to coincide with dates of administration of nivolumab and fluorouracil. Treatment length is determined treating investigator. The treating investigator may decide to discontinue fluorouracil therapy during treatment with 2141-V11 without impacting a patient’s ability to continue to receive 2141-V11 + nivolumab or other anti-PD-1 agent.
Patients also undergo esophagogastroduodenoscopy (EGD), endoscopic ultrasound (EUS), tumor biopsy with or without lymph node biopsy, positron emission tomography (PET) scan, computed tomography (CT) scan, magnetic resonance imaging (MRI), and blood and urine sample collection throughout the study. Patients may optionally undergo biopsy of metastatic lesions throughout the study.
After completion of treatment with 2141-V11, patients are followed up every 3 months for 2 years.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
