Clinical trial NCT04396821: A Trial to Evaluate Safety and Tolerability of TST001 in Advanced or Metastatic Solid Tumors
Official title: A Phase I/IIa Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of TST001 Administered as Monotherapy or in Combination With Nivolumab or Standard of Care in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Cancer
Gastric Cancer
Gastroesophageal-junction Cancer
Pancreatic Cancer
Lead sponsor: Suzhou Transcenta Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2020-05-21
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A - 2 arms, Q2w and Q3w, 3+3 design dose escalation; Part B - dose expansion, 3 Cohorts
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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 criteria: Inclusion Criteria:

* Male or female ≥ 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.

Exclusion Criteria

* Symptomatic central nervous system metastases.
* Prior treatment with any CLDN18.2 target agents
* Allergy or sensitivity to TST001 or known allergies to comparable drugs
* Documented history of multiple other allergies requiring interventions
* Severe cardiovascular disease, including CVA, TIA, myocardial infarction, or unstable angina, NYHA class III or IV heart failure or uncontrolled arrhythmia within 6 months of study entry, severe QTc prolongation, concomitant risks for QTc prolongation.
* Concurrent malignancy within 5 years prior to entry except adequately treated certain types of cancer
* Active and clinically significant infections, known uncontrolled infections with hepatitis B, hepatitis C, known human immunodeficiency virus with acquired immunodeficiency syndrome related illness
* Any condition that the investigator or primary physician believes may not be appropriate for participating in the study.

Other protocol-defined Inclusion/Exclusion Criteria could apply.

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Primary outcomes:
measure: Participant Safety as characterized by frequency and severity of adverse events
timeFrame: up to 100 days following last dose
measure: Maximum Tolerated Dose (MTD or Recommended Phase 2 Dose (RP2D)
timeFrame: up to 100 days following last dose
measure: Participant Safety and Tolerability of TST001 in combination with Nivolumab as characterized by frequency and severity of adverse events
timeFrame: Up to 100 days following last dose
measure: Participant Safety and Tolerability of TST001 in combination with Nivolumab and mFOLFOX6 as characterized by frequency and severity of adverse events
timeFrame: Up to 100 days following last dose
measure: Participant Safety and Tolerability of TST001 in combination with gemcitabine and albumin-bound paclitaxel as characterized by frequency and severity of adverse events
timeFrame: Up to 100 days following last dose
Secondary outcomes:
measure: Immunogenicity
timeFrame: up to 30 days following last dose
measure: Objective response rate (ORR)
timeFrame: up to 24 months, until disease progression or start of another anti-cancer therapy
measure: Duration of Response (DOR)
timeFrame: up to 24 months, until disease progression or start of another anti-cancer therapy
measure: Progression free survival (PFS)
timeFrame: up to 24 months, until disease progression or start of another anti-cancer therapy
measure: PK parameters
timeFrame: Up to 30 days following last dose
measure: PK
timeFrame: Up to 30 days following last dose
measure: PK
timeFrame: Up to 30 days following last dose
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas, School of Medicine
state: Kansas
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: New York City
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Research
state: Ohio
city: Gettysburg
country: United States
facility: Pennsylvania Cancer Specialist Research Institute
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Austin
country: United States
facility: NEXT Oncology
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Suzhou Transcenta Therapeutics Co.
name: Charlie Qi, MD
role: STUDY_DIRECTOR
References: