Dysautonomia International

A Study of 2141-V11 in People With Esophageal, Gastric, or Gastroesophageal Junction Adenocarcinoma

Purpose

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
Advanced Gastroesophageal Junction Adenocarcinoma
Esophageal Adenocarcinoma
Gastroesophageal Junction Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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

Phase: Phase 1/Phase 2
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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.	Biological: Intratumoral 2141-V11 2141-V11 is a recombinant fully humanized IgG1 monoclonal antibody directed against CD40, which activates the CD40 receptor. Biological: Nivolumab Nivolumab will be given as an intravenous infusion. Drug: Fluoropyrimidine 5-FU will be administered as a continuous infusion over 48 hours
Experimental Phase II	Should the intervention prove to be safe, the phase II component can be initiated with an expansion cohort.	Biological: Intratumoral 2141-V11 2141-V11 is a recombinant fully humanized IgG1 monoclonal antibody directed against CD40, which activates the CD40 receptor. Biological: Nivolumab Nivolumab will be given as an intravenous infusion. Drug: Fluoropyrimidine 5-FU will be administered as a continuous infusion over 48 hours

Recruiting Locations

Memorial Sloan Kettering at Basking Ridge (Limited protocol activities)
Basking Ridge, New Jersey 07920