This is an open label Phase I/IIa, First in Human trial of TST001, a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody as monotherapy or in combination with nivolumab or standard of care. It is being tested against advanced and/or metastatic solid tumors including gastric, gastroesophageal junction, pancreatic cancers.
Part A of the trial will consist of two cohorts, one dosed every 2 weeks and one dosed every 3 weeks in a standard 3+3 design. Part A is the dose finding portion of the trial. 18 to 36 participants will be enrolled. Part B consists of 3 cohorts: Cohort A is for patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma. Patients will receive TST001 at 2mg/kg or 4mg/kg Q2W plus Nivolumab and mFOLFOX6. Alternative allocation of patients between the 2 doses will be performed. The first 6 patients at each dose level as the lead-in phase will not be selected on the basis of their tumor's CLDN18.2 expression. Approximately 12-42 patients will be enrolled in Cohort A. Cohort B is for patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies. Patient will receive TST001 plus Nivolumab. No selection based on CLDN18.2 expression will be required for the safety run-in (3-6 patients). Patients with CLDN18.2 expression in tumor tissue tested by the central laboratory will be enrolled in the expansion phase. Safety run-in phase will follow 3+3 rule with two dose levels, TST001 3mg/kg and 6mg/kg Q3W combined with nivolumab. Approximately 30 patients will be enrolled in Cohort B including the patients in the safety run-in phase. Cohort C is for patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma; Patients will receive TST001 at 2mg/kg or 4mg/kg Q2W plus gemcitabine and albumin-bound paclitaxel. Alternative allocation of patients between the 2 doses will be performed. The first 6 patients at each dose level as the lead-in phase will not be selected on the basis of their tumor's CLDN18.2 expression. Approximately 12-42 patients will be enrolled in Cohort C.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
150
TST001 is a humanized IgG1 monoclonal antibody.
Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies
mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.
Chemotherapy medication
Chemotherapy medication
Banner MD Anderson
Gilbert, Arizona, United States
University of Arizona
Tucson, Arizona, United States
Yale University
New Haven, Connecticut, United States
Florida Cancer Specialists
Sarasota, Florida, United States
Emory University
Atlanta, Georgia, United States
University of Kansas, School of Medicine
Kansas City, Kansas, United States
Washington University
St Louis, Missouri, United States
Memorial Sloan Kettering
New York, New York, United States
Stony Brook Cancer Center
Stony Brook, New York, United States
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
...and 8 more locations
Participant Safety as characterized by frequency and severity of adverse events
Characterization of TST001 safety profile including frequency and severity of adverse events that are related to treatment.
Time frame: up to 100 days following last dose
Maximum Tolerated Dose (MTD or Recommended Phase 2 Dose (RP2D)
As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort
Time frame: up to 100 days following last dose
Participant Safety and Tolerability of TST001 in combination with Nivolumab as characterized by frequency and severity of adverse events
Characterization of TST001 + Nivolumab safety profile including frequency and severity of adverse events that are related to treatment.
Time frame: Up to 100 days following last dose
Participant Safety and Tolerability of TST001 in combination with Nivolumab and mFOLFOX6 as characterized by frequency and severity of adverse events
Characterization of TST001 + Nivolumab + mFOLFOX6 safety profile including frequency and severity of adverse events that are related to treatment.
Time frame: Up to 100 days following last dose
Participant Safety and Tolerability of TST001 in combination with gemcitabine and albumin-bound paclitaxel as characterized by frequency and severity of adverse events
Characterization of TST001 + Gemcitabine + albumin-bound paclitaxel safety profile including frequency and severity of adverse events that are related to treatment.
Time frame: Up to 100 days following last dose
Immunogenicity
by measurement of Incidence of anti-drug antibodies (ADA)
Time frame: up to 30 days following last dose
Objective response rate (ORR)
as measured by RECIST 1.1
Time frame: up to 24 months, until disease progression or start of another anti-cancer therapy
Duration of Response (DOR)
duration of response (DOR)
Time frame: up to 24 months, until disease progression or start of another anti-cancer therapy
Progression free survival (PFS)
as measured by RECIST v1.1
Time frame: up to 24 months, until disease progression or start of another anti-cancer therapy
PK parameters
Maximum serum concentration (Cmax)
Time frame: Up to 30 days following last dose
PK
time to reach maximum serum concentration (Tmax)
Time frame: Up to 30 days following last dose
PK
Area Under the Curve
Time frame: Up to 30 days following last dose
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