Advanced Esophageal Cancer, Advanced Gastric Cancer, Advanced Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Esophageal Cancer, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Gastroesophageal Junction Cancer
Conditions
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
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
Interventions
BIOLOGICALIntratumoral 2141-V11
2141-V11 is a recombinant fully humanized IgG1 monoclonal antibody directed against CD40, which activates the CD40 receptor.
BIOLOGICALNivolumab
Nivolumab will be given as an intravenous infusion.
DRUGFluoropyrimidine
5-FU will be administered as a continuous infusion over 48 hours
Sponsors
Memorial Sloan Kettering Cancer Center
Rockefeller University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate safety of intratumoral 2141-V11 | 6 weeks | The primary endpoint of the safety lead-in cohort is safety. Safety is defined as the incidence of dose-limiting toxicities (DLTs) during the 6-week DLT evaluation window. |
Countries
United States
Contacts
CONTACTSamuel Cytryn, MD
CONTACTSeung Eun Lee, MD
PRINCIPAL_INVESTIGATORSamuel Cytryn, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed