Recruiting
Phase 1
Phase 2

2141-V11 with Anti-PD-1

Sponsor:

Memorial Sloan Kettering Cancer Center

Code:

NCT07818018

Conditions

Esophageal Cancer

Advanced Esophageal Cancer

Gastric Cancer

Advanced Gastric Cancer

Gastroesophageal Junction Adenocarcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Intratumoral 2141-V11

Nivolumab

Fluoropyrimidine

Study Details

Brief summary:

The purpose of this study is to find out whether adding the drug 2141-V11 to standard treatment (anti-PD-1 immunotherapy with or without 5-FU) is a safe treatment approach for participants with advanced esophageal, gastric, or gastroesophageal junction adenocarcinoma

Conditions

Esophageal Cancer

Advanced Esophageal Cancer

Gastric Cancer

Advanced Gastric Cancer

Gastroesophageal Junction Adenocarcinoma

Study ID

NCT07818018

Start date

Sep 4, 2026

Status verified date

Sep, 2026

Completion date

Sep 4, 2029

Anticipated

Primary completion date

Sep 4, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Histologically confirmed esophageal, gastric, or gastroesophageal junction adenocarcinoma
  • Locally advanced unresectable or metastaticdisease at diagnosis
  • On first line systemic therapy including fluoropyrimidine + anti-PD-1 therapy for advanced GEA (e.g. 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 v1.1
  • Able to undergo endoscopy
  • Age 18 years or older
  • ECOG performance status 0 to 1 (See Appendix I for performance status criteria)
  • Adequate organ function as defined by:

  • Absolute neutrophil count ≥1000/mcL
  • Platelets ≥90,000/mcL
  • Hemoglobin ≥8 g/dL
  • Serum creatinine ≤1.5X ULN
  • Serum total bilirubin ≤1.5X ULN OR Direct bilirubin ≤ULN for participants with total bilirubin levels >1.5X ULN, except patients with Gilbert's disease (≤3X ULN)
  • AST and ALT ≤3X ULN
  • Albumin ≥3 mg/dL Abbreviations: ALT, alanine aminotransferase; AST, aminotransferase; ULN, upper limit of normal.

Exclusion Criteria:

  • Mismatch repair deficient (dMMR) disease by 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 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, HBV, and 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 Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase Ib

Lead-in cohort. The intervention will be considered safe if DLT's are observed in <2 of the first 6 patients enrolled; the observation of 2 or more DLTs in the first 6 patients will trigger dose deescalation to dose level -1 (3 mg); should this occur, 6 more patients will be enrolled at dose level -1. If 2 or more DLT's are then observed at dose level -1, the study will be paused and accrual will be stopped to reconsider 2141-V11 dosage.

experimental: Phase II

Should the intervention prove to be safe, the phase II component can be initiated with an expansion cohort.

Interventions

Intratumoral 2141-V11

2141-V11 is a recombinant fully humanized IgG1 monoclonal antibody directed against CD40, which activates the CD40 receptor.

Nivolumab

Nivolumab will be given as an intravenous infusion.

Fluoropyrimidine

5-FU will be administered as a continuous infusion over 48 hours

Primary outcome measure

  • Evaluate safety of intratumoral 2141-V11 [ Time Frame: 6 weeks ]

Central Contacts and Locations

Central contacts

Samuel Cytryn, MD

646-888-4896CytrynS@mskcc.org

Seung Eun Lee, MD

212-639-3754LeeS25@mskcc.org

Locations

Memorial Sloan Kettering at Basking Ridge (Limited protocol activities)

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Samuel Cytryn, MD

646-888-4896CytrynS@mskcc.org

Memorial Sloan Kettering at Monmouth (Limited Protocol Activities)

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Samuel Cytryn, MD

646-888-4896CytrynS@mskcc.org

Memorial Sloan Kettering at Bergen (Limited Protocol Activities)

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Samuel Cytryn, MD

646-888-4896CytrynS@mskcc.org

Memorial Sloan Kettering at Suffolk-Commack (Limited Protocol Activities)

Recruiting

Commack, New York, United States, 11725

Contacts

Samuel Cytryn, MD

646-888-4896CytrynS@mskcc.org

Memorial Sloan Kettering at Westchester (Limited Protocol Activities)

Recruiting

Harrison, New York, United States, 10604

Contacts

Samuel Cytryn, MD

646-888-4896CytrynS@mskcc.org

Memorial Sloan Kettering Cancer Center (All Protocol Activites)

Recruiting

New York, New York, United States, 10065

Contacts

Samuel Cytryn, MD

646-888-4896CytrynS@mskcc.org

Memorial Sloan Kettering at Nassau (Limited protocol activities)

Recruiting

Uniondale, New York, United States, 11553

Contacts

Samuel Cytryn, MD

646-888-4896CytrynS@mskcc.org

More Information

Sponsor

Memorial Sloan Kettering Cancer Center

Last update posted

Sep 14, 2026

Last verified

Sep, 2026

Keywords

  • Esophageal Cancer
  • advanced esophageal cancer
  • Gastric cancer
  • Advanced Gastric Cancer
  • gastroesophageal junction adenocarcinoma
  • Advanced Gastroesophageal Junction Adenocarcinoma
  • esophageal adenocarcinoma
  • gastroesophageal junction cancer
  • 26-267
  • Memorial Sloan Kettering Cancer Center

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-15. This information was provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center on 2026-09-14.