Clinical trial NCT06251973: A Study of agenT-797 in Combination With Botensilimab, Balstilimab, Ramucirumab, and Paclitaxel for People With Esophageal, Gastric, or Gastro-esophageal Junction Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: 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
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
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2024-02-09
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Overall Response Rate
timeFrame: up to 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Limited Protocol Activities)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Suffolk-Commack (Limited protocol activities)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Limited Protocol Activities)
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (All Protocol Activities)
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Limited Protocol Activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Yelena Janjigian, MD
role: PRINCIPAL_INVESTIGATOR
References: