RecruitingPhase 2NCT06251973

A Study of agenT-797 in Combination With Botensilimab, Balstilimab, Ramucirumab, and Paclitaxel for People With Esophageal, Gastric, or Gastro-esophageal Junction Cancer

A Phase II Study of agenT-797 (Invariant Natural Killer T Cells), Botensilimab, a Novel Fc-enhanced CTLA-4 Inhibitor, Plus Balstilimab (Anti-PD-1) With Ramucirumab and Paclitaxel for Patients With Previously Treated, Advanced Esophageal, Gastric, or Gastro-esophageal Junction Adenocarcinoma

Sponsor

Memorial Sloan Kettering Cancer Center

Enrollment

37 participants

Start Date

Feb 1, 2024

Study Type

INTERVENTIONAL

Conditions

Metastatic Gastric Adenocarcinoma Metastatic Gastroesophageal Junction Adenocarcinoma Unresectable Gastric Adenocarcinoma Unresectable Gastroesophageal Junction Adenocarcinoma Metastatic Gastric Carcinoma Metastatic Gastric Cancer Metastatic Esophageal Carcinoma Unresectable Gastric Carcinoma Metastatic Esophageal Adenocarcinoma Unresectable Esophageal Adenocarcinoma Advanced Unresectable Gastric Adenocarcinoma Metastatic Esophageal Cancer Unresectable Esophageal Cancer

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria8

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 Criteria15

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

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.