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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04396821
Recruitment Status : Recruiting
First Posted : May 21, 2020
Last Update Posted : January 20, 2023
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Suzhou Transcenta Therapeutics Co., Ltd.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Cancer Gastric Cancer Gastroesophageal-junction Cancer Pancreatic Cancer Drug: TST001 Drug: Nivolumab Injection [Opdivo] Drug: mFOLFOX6 Drug: Gemcitabine Drug: Albumin-Bound Paclitaxel Phase 1 Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Part A - 2 arms, Q2w and Q3w, 3+3 design dose escalation; Part B - dose expansion, 3 Cohorts
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 28, 2020
Estimated Primary Completion Date : June 30, 2024
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part A Q2W
Dosed every 2 weeks IV with TST001, starting dose is 1 mg/kg, multiple dose levels will be tested.
 Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.
Experimental: Part A Q3W
Dosed every 3 weeks IV with TST001, starting dose is 3 mg/kg, and multiple dose levels will be tested.
 Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.
Experimental: Part B Cohort A
Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma.
 Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.

Drug: Nivolumab Injection [Opdivo]
Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies

Drug: mFOLFOX6
mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.
Experimental: Part B Cohort B
Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies.
 Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.

Drug: Nivolumab Injection [Opdivo]
Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies
Experimental: Part B Cohort C
Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma.
 Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.

Drug: Gemcitabine
Chemotherapy medication
Other Name: Gemzar

Drug: Albumin-Bound Paclitaxel
Chemotherapy medication


Outcome Measures
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Primary Outcome Measures :
  1. Participant Safety as characterized by frequency and severity of adverse events [ Time Frame: up to 100 days following last dose ]
    Characterization of TST001 safety profile including frequency and severity of adverse events that are related to treatment.

  2. Maximum Tolerated Dose (MTD or Recommended Phase 2 Dose (RP2D) [ Time Frame: up to 100 days following last dose ]
    As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort

  3. Participant Safety and Tolerability of TST001 in combination with Nivolumab as characterized by frequency and severity of adverse events [ Time Frame: Up to 100 days following last dose ]
    Characterization of TST001 + Nivolumab safety profile including frequency and severity of adverse events that are related to treatment.

  4. Participant Safety and Tolerability of TST001 in combination with Nivolumab and mFOLFOX6 as characterized by frequency and severity of adverse events [ Time Frame: Up to 100 days following last dose ]
    Characterization of TST001 + Nivolumab + mFOLFOX6 safety profile including frequency and severity of adverse events that are related to treatment.

  5. Participant Safety and Tolerability of TST001 in combination with gemcitabine and albumin-bound paclitaxel as characterized by frequency and severity of adverse events [ Time Frame: Up to 100 days following last dose ]
    Characterization of TST001 + Gemcitabine + albumin-bound paclitaxel safety profile including frequency and severity of adverse events that are related to treatment.


Secondary Outcome Measures :
  1. Immunogenicity [ Time Frame: up to 30 days following last dose ]
    by measurement of Incidence of anti-drug antibodies (ADA)

  2. Objective response rate (ORR) [ Time Frame: up to 24 months, until disease progression or start of another anti-cancer therapy ]
    as measured by RECIST 1.1

  3. Duration of Response (DOR) [ Time Frame: up to 24 months, until disease progression or start of another anti-cancer therapy ]
    duration of response (DOR)

  4. Progression free survival (PFS) [ Time Frame: up to 24 months, until disease progression or start of another anti-cancer therapy ]
    as measured by RECIST v1.1

  5. PK parameters [ Time Frame: Up to 30 days following last dose ]
    Maximum serum concentration (Cmax)

  6. PK [ Time Frame: Up to 30 days following last dose ]
    time to reach maximum serum concentration (Tmax)

  7. PK [ Time Frame: Up to 30 days following last dose ]
    Area Under the Curve


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04396821


Contacts
Layout table for location contacts
Contact: Angela Ireland, MS 980-258-9780 angela.ireland@wuxiapptec.com

Locations
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Sponsors and Collaborators
Suzhou Transcenta Therapeutics Co., Ltd.
Bristol-Myers Squibb
Investigators
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Study Director: Caroline Germa, MD Suzhou Transcenta Therapeutics Co.
More Information
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Responsible Party: Suzhou Transcenta Therapeutics Co., Ltd.
ClinicalTrials.gov Identifier: NCT04396821    
Other Study ID Numbers: TST001-1001
First Posted: May 21, 2020    Key Record Dates
Last Update Posted: January 20, 2023
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: As described below. Patient personal data will be kept confidential as per HIPAA.
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Time Frame: Clinical Study Report will become available approximately 60 to 90 days after last patient last visit. Each Investigator will receive one to keep. Protocol will be received prior to study start for each investigator.
Access Criteria: Be an active investigator in the TST001-1001 trial

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Paclitaxel
Gemcitabine
Nivolumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
 Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors