Advanced Unresectable Gastric Adenocarcinoma, Metastatic Esophageal Adenocarcinoma, Metastatic Esophageal Cancer, Metastatic Esophageal Carcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastric Cancer, Metastatic Gastric Carcinoma, Metastatic Gastroesophageal Junction Adenocarcinoma, Unresectable Esophageal Adenocarcinoma, Unresectable Esophageal Cancer, Unresectable Gastric Adenocarcinoma, Unresectable Gastric Carcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma
Conditions
Keywords
Metastatic Esophageal Carcinoma, Advanced Unresectable Gastric Adenocarcinoma, Metastatic Gastric Cancer, Metastatic Gastroesophageal Junction Adenocarcinoma, Metastatic Esophageal Cancer, Metastatic Esophageal Adenocarcinoma, Metastatic Gastric Adenocarcinoma, Metastatic Gastric Carcinoma, Unresectable Esophageal Cancer, Unresectable Esophageal Adenocarcinoma, Unresectable Gastric Carcinoma, Unresectable Gastric Adenocarcinoma, Unresectable Gastroesophageal Junction Adenocarcinoma, 23-261, Memorial Sloan Kettering Cancer Center
Brief summary
Participants will receive study treatment with agenT-797, botensilimab, balstilimab, ramucirumab, and paclitaxel. When participants start each agent will depend on how their disease is affecting them.
Interventions
BIOLOGICALAgenT-797
AgenT-797 is an investigational product, composed of allogeneic human unmodified iNKT cells, isolated from mononuclear cell aphaeresis units from healthy donors
BIOLOGICALBotensilimab
Botensilimab is a novel, human, Fc-engineered IgG1 anti-CTLA-4 antibody
DRUGBalstilimab
Botensilimab is supplied as a sterile, single-use solution for IV administration
DRUGRamucirumab
Ramucirumab is a fully human anti-VEGFR2 monoclonal IgG1 antibody (IgG1) that binds with high affinity to the extracellular domain of VEGFR2. Ramucirumab is a part of standard of care treatment for advanced gastric cancer or GEJ adenocarcinoma, after prior treatment with fluoropyrimidine- or platinum-containing chemotherarapy.
DRUGPaclitaxel
Paclitaxel is widely used across multiple cancer types and is a part of standard of care treatment for advanced EG adenocarcinoma after prior treatment with fluoropyrimidine- or platinum-containing chemotherarapy.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Metastatic or advanced unresectable adenocarcinoma of esophageal, gastric, or gastroesophageal junction * Disease progression on one prior line of therapy for metastatic disease. Patients with previously untreated advanced unresectable or metastatic disease may be included if disease progressed or recurred during neoadjuvant or adjuvant therapy or within 6 months of completion of those treatments. * Patients must have histologically or cytologically confirmed esophageal, gastric, or gastroesophageal junction adenocarcinoma * Patients must have measurable or evaluable disease as defined by RECIST v1.1 criteria. Patients with evaluable disease must be eligible to begin with an induction cycle * Age 18 years or older * ECOG performance status 0 to 1 * Adequate organ function as defined in Table 2 Table 2. Organ function requirements for eligibility Hematological Absolute neutrophil count: ≥1000/mcL Platelets: ≥90,000/mcL Hemoglobin: ≥8 g/dL Renal Serum creatinine: ≤1.5X ULN Hepatic Serum total bilirubin: ≤1.5X ULN OR Direct bilirubin ≤ULN for subjects with total bilirubin levels \>1.5X ULN, except patients with Gilbert's disease (≤3X ULN) AST and ALT: ≤2.5X ULN Albumin: ≥3 mg/dL
Exclusion criteria
* Received prior therapy with ramucirumab at any time * Received paclitaxel or docetaxel-based therapy within 6 month of study enrollment * Had a prior grade \>3 immune related adverse event due to anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 therapy at any time * Diagnosis of immunodeficiency or receipt of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment. Replacement therapy (ie physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic immunosuppressive therapy and is allowed. * History of gastrointestinal perforation or fistulae * A known history of active Bacillus tuberculosis * Known active central nervous system metastases and/or carcinomatous meningitis * History of or any evidence of active, non-infectious, immune-mediated pneumonitis. Patients with radiation-induced pneumonitis who are asymptomatic are permitted on study. * Peripheral neuropathy limiting ADLs * A known history of human immunodeficiency virus (HIV 1/2 antibodies) * Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA \[qualitative\] is detected). Patients with HBsAg reactive on entecavir may be eligible after consultation with hepatologist and study team. * Received a live vaccine within 30 days of planned start of study therapy * Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial * Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 5 months after the last dose of trial treatment * 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 |
|---|---|---|
| Overall Response Rate | up to 2 years | Determine the efficacy of agenT-797, botensilimab and balstilimab in combination with ramucirumab and paclitaxel as second-line therapy in patients with advanced unresectable or metastatic esophagogastric cancer, as measured by ORR (defined as the percentage of patients who achieve either an objective complete response \[CR\] + partial response \[PR\]) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORYelena Janjigian, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed