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

Metastatic Gastric Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06251973
• Other study ID #: 23-361
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2024
• Est. completion date: August 1, 2027

Study information

• Verified date: May 2024
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Yelena Janjigian, MD
• Phone: 646-888-4186
• Email: janjigiy[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 38
• Est. completion date: August 1, 2027
• Est. primary completion date: August 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 pneumonitis

• 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Carcinoma
• Esophageal Neoplasms
• Metastatic Esophageal Adenocarcinoma
• Metastatic Esophageal Cancer
• Metastatic Esophageal Carcinoma
• Metastatic Gastric Adenocarcinoma
• Metastatic Gastric Cancer
• Metastatic Gastric Carcinoma
• Metastatic Gastroesophageal Junction Adenocarcinoma
• Stomach Neoplasms
• Unresectable Esophageal Adenocarcinoma
• Unresectable Esophageal Cancer
• Unresectable Gastric Adenocarcinoma
• Unresectable Gastric Carcinoma
• Unresectable Gastroesophageal Junction Adenocarcinoma

Intervention

Biological:
• AgenT-797
AgenT-797 is an investigational product, composed of allogeneic human unmodified iNKT cells, isolated from mononuclear cell aphaeresis units from healthy donors
• Botensilimab
Botensilimab is a novel, human, Fc-engineered IgG1 anti-CTLA-4 antibody

Drug:
• Balstilimab
Botensilimab is supplied as a sterile, single-use solution for IV administration
• Ramucirumab
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.
• Paclitaxel
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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)	Basking Ridge	New Jersey
United States	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 Monmouth (Limited Protocol Activities)	Middletown	New Jersey
United States	Memorial Sloan Kettering Bergen (Limited Protocol Activities)	Montvale	New Jersey
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

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	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])	up to 2 years

External Links

•   Memorial Sloan Kettering Cancer Center