A Trial to Evaluate Safety and Tolerability of TST001 in Advanced or Metastatic Solid Tumors
Bile Duct Cancer
Pancreatic Cancer
Stomach/ Gastric Cancer
18 Years and older, Male and Female
TST001-1001 (primary)
NCI-2020-05881
Summary
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.
Objectives
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.
Eligibility
- Male or female â?¥ 18 years.
- Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors. Part A only: * Patients must be: a) progressed after standard therapies, b) intolerant of standard
therapies, or c) with a tumor type without standard therapy. Part B only:
- Cohort A: Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma; prior adjuvant or neoadjuvant therapy are allowed only if disease progressed or recurred at least 6 months after completion of these treatments. Patients may have received one infusion of mFOLFOX6 plus nivolumab during the screening period.
- Cohort B: Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies; adjuvant or neoadjuvant therapy could be regarded as one line of therapy only if disease progressed or recurred during these treatments or within 6 months or less after completion of these treatments.
- Cohort C: Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma; prior adjuvant or neoadjuvant therapy are allowed only if disease progressed or recurred at least 6 months after completion of these treatments. Patients may have received up to 2 infusions of Gemcitabine + albumin-bound paclitaxel (with one week between each infusion) during the screening period.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 .
- Patients with adequate cardiac, liver, renal function, etc.
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
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