Combination treatment for advanced esophageal and gastric cancers

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

Phase 2 Interventional Memorial Sloan Kettering Cancer Center · NCT06251973

This study is testing a combination of five different treatments to see if they can help people with advanced esophageal and gastric cancers feel better and live longer.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment37 (estimated)
Ages18 Years and up
SexAll
SponsorMemorial Sloan Kettering Cancer Center Academic / other
Drugs / interventionsramucirumab, radiation, botensilimab, balstilimab
Locations7 sites (Basking Ridge, New Jersey and 6 other locations)
Trial IDNCT06251973 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of a combination treatment involving agenT-797, botensilimab, balstilimab, ramucirumab, and paclitaxel for patients with metastatic or advanced unresectable esophageal and gastric cancers. Participants will receive these treatments based on their disease progression and response to therapy. The goal is to determine the safety and efficacy of this multi-agent regimen in improving patient outcomes.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with metastatic or advanced unresectable adenocarcinoma of the esophagus, stomach, or gastroesophageal junction who have experienced disease progression on prior therapy.

Not a fit: Patients with early-stage or resectable cancers, or those who have not progressed on prior therapies, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced esophageal and gastric cancers that have not responded to previous therapies.

How similar studies have performed: Other studies have shown promise with similar multi-agent approaches in treating advanced cancers, indicating potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria
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

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Metastatic Esophageal CarcinomaAdvanced Unresectable Gastric AdenocarcinomaMetastatic Gastric CancerMetastatic Gastroesophageal Junction AdenocarcinomaMetastatic Esophageal CancerMetastatic Esophageal AdenocarcinomaMetastatic Gastric AdenocarcinomaMetastatic Gastric Carcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.