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

Phase 2

Recruiting

• Conditions: Unresectable Esophageal Adenocarcinoma; Unresectable Gastric Carcinoma; Unresectable Gastric Adenocarcinoma; Unresectable Gastroesophageal Junction Adenocarcinoma; Metastatic Esophageal Cancer; Metastatic Gastric Carcinoma; Metastatic Esophageal Carcinoma; Advanced Unresectable Gastric Adenocarcinoma; Metastatic Esophageal Adenocarcinoma; Metastatic Gastric Adenocarcinoma
• Interventions: Biological: AgenT-797; Biological: Botensilimab; Drug: Balstilimab; Drug: Ramucirumab; Drug: Paclitaxel

• Registration Number: NCT06251973
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-01
• Study First Submitted: 2024-02-01
• Study First Submitted QC: 2024-02-01
• Study First Posted: 2024-02-09
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-17
• Last Update Posted: 2025-04-23
• Primary Completion: 2027-08-01
• Study Completion: 2027-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 37

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants diagnoses with Esophageal, Gastric, or Gastro-esophageal Junction Cancer	Botensilimab	Participants with measurable disease and with evaluable disease as defined by RECIST v1.1 will be enrolled on this study.
Participants diagnoses with Esophageal, Gastric, or Gastro-esophageal Junction Cancer	AgenT-797	Participants with measurable disease and with evaluable disease as defined by RECIST v1.1 will be enrolled on this study.
Participants diagnoses with Esophageal, Gastric, or Gastro-esophageal Junction Cancer	Ramucirumab	Participants with measurable disease and with evaluable disease as defined by RECIST v1.1 will be enrolled on this study.
Participants diagnoses with Esophageal, Gastric, or Gastro-esophageal Junction Cancer	Paclitaxel	Participants with measurable disease and with evaluable disease as defined by RECIST v1.1 will be enrolled on this study.
Participants diagnoses with Esophageal, Gastric, or Gastro-esophageal Junction Cancer	Balstilimab	Participants with measurable disease and with evaluable disease as defined by RECIST v1.1 will be enrolled on this study.

Primary Outcome Measures

Name	Time	Method
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 \[PR\])

Trial Locations

Locations (7)

Memorial Sloan Kettering Suffolk-Commack (Limited protocol activities); 🇺🇸 Commack, New York, United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities); 🇺🇸 Harrison, New York, United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities); 🇺🇸 New York, New York, United States

Memorial Sloan Kettering Nassau (Limited Protocol Activities); 🇺🇸 Uniondale, New York, United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities); 🇺🇸 Middletown, New Jersey, United States

Memorial Sloan Kettering Bergen (Limited Protocol Activities); 🇺🇸 Montvale, New Jersey, United States

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities); 🇺🇸 Basking Ridge, New Jersey, United States