A Trial to Evaluate Safety and Tolerability of TST001 in Advanced or Metastatic Solid Tumors

Pancreatic Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04396821
• Other study ID #: TST001-1001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 28, 2020
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Suzhou Transcenta Therapeutics Co., Ltd.
• Contact: Angela Ireland, MS
• Phone: 980-258-9780
• Email: angela.ireland[@]wuxiapptec.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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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Related Conditions & MeSH terms

• Advanced Cancer
• Gastric Cancer
• Gastroesophageal-junction Cancer
• Pancreatic Cancer

Intervention

Drug:
• TST001
TST001 is a humanized IgG1 monoclonal antibody.
• Nivolumab Injection [Opdivo]
Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies
• mFOLFOX6
mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.
• Gemcitabine
Chemotherapy medication
• Albumin-Bound Paclitaxel
Chemotherapy medication

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	NEXT Oncology	Austin	Texas
United States	Gabrail Cancer Research	Canton	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Pennsylvania Cancer Specialist Research Institute	Gettysburg	Pennsylvania
United States	Banner MD Anderson	Gilbert	Arizona
United States	University of Kansas, School of Medicine	Kansas City	Kansas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt University	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering	New York	New York
United States	Allegheny Hospital	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Swedish Cancer Institute	Seattle	Washington
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	University of Arizona	Tucson	Arizona
United States	Wake Forest Baptist Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Suzhou Transcenta Therapeutics Co., Ltd.	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 100 days following last dose
Primary	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	up to 100 days following last dose
Primary	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.	Up to 100 days following last dose
Primary	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.	Up to 100 days following last dose
Primary	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.	Up to 100 days following last dose
Secondary	Immunogenicity	by measurement of Incidence of anti-drug antibodies (ADA)	up to 30 days following last dose
Secondary	Objective response rate (ORR)	as measured by RECIST 1.1	up to 24 months, until disease progression or start of another anti-cancer therapy
Secondary	Duration of Response (DOR)	duration of response (DOR)	up to 24 months, until disease progression or start of another anti-cancer therapy
Secondary	Progression free survival (PFS)	as measured by RECIST v1.1	up to 24 months, until disease progression or start of another anti-cancer therapy
Secondary	PK parameters	Maximum serum concentration (Cmax)	Up to 30 days following last dose
Secondary	PK	time to reach maximum serum concentration (Tmax)	Up to 30 days following last dose
Secondary	PK	Area Under the Curve	Up to 30 days following last dose