A Phase 1b/II Study of Intratumoral CD40 Agonist 2141-V11 in Combination With Anti PD-1 and 5-Fluorouracil Therapy in Patients With Advanced Gastroesophageal Adenocarcinoma
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 30
- Locations
- 7
- Primary Endpoint
- Evaluate safety of intratumoral 2141-V11
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- 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
Arms & Interventions
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.
Intervention: Intratumoral 2141-V11 (Biological)
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.
Intervention: Fluoropyrimidine (Drug)
Phase II
Should the intervention prove to be safe, the phase II component can be initiated with an expansion cohort.
Intervention: Intratumoral 2141-V11 (Biological)
Phase II
Should the intervention prove to be safe, the phase II component can be initiated with an expansion cohort.
Intervention: Fluoropyrimidine (Drug)
Phase II
Should the intervention prove to be safe, the phase II component can be initiated with an expansion cohort.
Intervention: Nivolumab (Biological)
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.
Intervention: Nivolumab (Biological)
Outcomes
Primary Outcomes
Evaluate safety of intratumoral 2141-V11
Time Frame: 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.
Secondary Outcomes
No secondary outcomes reported