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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 : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
Mabspace Biosciences (Suzhou) Co., Ltd.

Brief Summary:
This is an open label Phase 1, First in Human trial of TST001, a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody. It is being tested against advanced and/or metastatic solid tumors including gastric, gastroesophageal junction, pancreatic, colon and lung cancers.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: TST001 Phase 1

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.

27 to 54 participants will be enrolled.

Part B consists of 3 cohorts of approximately 20 participants each. For Part B, participants must have CLDN18.2 expressing tumors to qualify for participation. Cohort 1 is for participants with gastric and gastroesophageal junction cancers and dosed every 2 weeks. Cohort 2 is for participants with solid tumors except gastric and gastroesophageal cancers, dosed every 2 weeks. Cohort 3 is for all solid tumors dosed every 3 weeks. Up to 60 participants will be enrolled.

The trial will last approximately 2 years, with assessments including safety labs, ECGs, MUGA scans, PKs and PDs and CT/MRI tumor assessments, based on the Q2W and Q3W dosing schedules.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 114 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 of 20 patients each
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of TST001 in Patients With Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date : May 28, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : April 1, 2023

Arm Intervention/treatment
Experimental: Part A Q2W
Dosed every 2 weeks IV with TST001, starting dose is 1 mg/kg, 5 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 4 dose levels will be tested.
Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.

Experimental: Part B Cohort 1
Participants with gastric or gastroesophageal junction cancers CLDN18.2 expression, dosed Q2W IV with the Part A Q2W recommended dose.
Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.

Experimental: Part B Cohort 2
Participants with solid tumors other than gastric or gastroesophageal junction cancers with CLDN18.2 expression dosed Q2W IV with TST001 as above.
Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.

Experimental: Part B Cohort 3
Participants with any kind of advanced or metastatic solid tumors with CLDN 18.2 expression, dosed Q3W with the Part A Q3W recommended dose of TST001
Drug: TST001
TST001 is a humanized IgG1 monoclonal antibody.




Primary Outcome Measures :
  1. Participant Safety as characterized by frequency and severity of adverse events [ Time Frame: up to 90 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 90 days following last dose ]
    As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort


Secondary Outcome Measures :
  1. Area under plasma concentration vs time curve (AUC) for TST001 [ Time Frame: up to 30 days following last dose ]
    changes in AUC over time in participants with TST001

  2. Peak plasma concentration (Cmax) for TST001 [ Time Frame: up to 30 days following last dose ]
    Cmax is the maximum plasma concentration

  3. Time to maximum observed plasma concentration (Tmax) [ Time Frame: up to 30 days following last dose ]
    Tmax is the time in hrs/days it takes to reach Cmax after dosing with TST001

  4. Terminal elimination half life (t1/2) [ Time Frame: up to 30 days following last dose ]
    Time for the plasma level of TST001 to decrease b y 1/2 during the terminal elimination phase

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

  6. Objective response rate (ORR) [ Time Frame: up to 90 days following last dose ]
    as measured by RECIST 1.1

  7. Duration of Response (DOR) [ Time Frame: up to 90 days following last dose ]
    duration of response (DOR)

  8. Clinical Benefit Rate [ Time Frame: up to 90 days following last dose ]
    (CBR: CR+PR+SD ≥ 18 weeks)

  9. Progression free survival (PFS) [ Time Frame: up to 90 days following last dose ]
    as measured by RECIST v1.1



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:

  1. Willing and able to provide signed and dated informed consent
  2. Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors.
  3. Patients must be: a) progressed after standard therapies, b) intolerant of standard therapies, or c) with a tumor type without standard therapy. d) Patients with HER2+ GC/GEJ cancer must have progressed after HER2-targeted therapy.
  4. CLDN18.2 expression in tumor (Part B only): patients with locally advanced or metastatic unresectable GC, GEJ cancer, or other solid tumor including but not limited to pancreatic cancer, cholangiocarcinoma, ovarian cancer, and lung cancer.
  5. Eastern Cooperative Oncology Group Performance Status (ECOG PS): Part A 0~1, Part B 0~2.
  6. Life expectancy ≥ 3 months.
  7. At least one measurable lesion per RECIST 1.1 (Part B only).
  8. Provide archived tumor tissue samples
  9. Adequate organ function
  10. Recover to Grade 0-1 from adverse events related to prior anti-cancer therapy except alopecia

Exclusion Criteria:

  1. Symptomatic central nervous system metastases.
  2. Prior anticancer therapy:

    1. Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, or targeted therapy) within 4 weeks prior to Cycle 1 Day 1, or chemotherapy without delayed toxicity within the last 2 weeks preceding the first dose of study treatment with ≤ grade 1 treatment related AEs.
    2. Radiation therapy within 4 weeks prior to Cycle 1 Day 1;
    3. Prior treatment with an anti-CLDN18.2 antibody.
  3. Major surgery within 8 weeks prior to study entry; Minor surgery within 2 weeks prior to study entry.
  4. Gastrointestinal abnormalities including:

    1. Documented unresolved gastric outlet obstruction or persistent vomiting defined as ≥3 episodes within 24 hours
    2. Active peptic ulcer disease required treatment in the past 3 months
    3. Gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
    4. Documented active colitis within 4 weeks prior to study entry, including infectious colitis, radiation colitis and ischemic colitis
    5. History of ulcerative colitis or Crohn's disease
  5. Allergy or sensitivity to TST001 or known allergies to antibodies produced from Chinese hamster ovary cells, which in the opinion of the investigator suggests an increased potential for hypersensitivity to TST001.
  6. History of a Grade 3-4 allergic reaction to treatment with another monoclonal antibody.
  7. Severe cardiovascular disease.
  8. QTc ≥470ms at baseline.
  9. Concurrent malignancy within 5 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer not requiring treatment (with or without resection), ductal carcinoma in situ of the breast, or ≤ T1 urothelial carcinoma.
  10. Prior stem cell, bone marrow or solid organ transplant.
  11. Active infection requiring intravenous therapy within 2 weeks prior to entry.
  12. Women of childbearing potential, unless they are using highly effective methods of contraception during the intervention period and for 90 days after the last dose of study intervention.
  13. Men with a partner of childbearing potential who do not consent to use two highly effective methods of birth control during treatment and for an additional 90 days after the last administration of investigational drug.
  14. Any condition that the investigator or primary physician believes may not be appropriate for participating the study.

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
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Contact: Sally Fisher, BSN 813 395 4638 sally.fisher@wuxiapptec.com
Contact: Catherine Holloway, MSc 512-221-8333 catherine.holloway@wuxiapptec.com

Locations
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United States, Texas
NEXT Oncology Recruiting
Austin, Texas, United States, 78704
Contact: Ronald Theodore, MS       rtheodore@nextoncology.com   
Contact: Theresa Mays, PharmD       tmays@nextoncology.com   
Principal Investigator: Anthony W Tolcher, MD         
Sub-Investigator: Raghad Karim, MD         
Sponsors and Collaborators
Mabspace Biosciences (Suzhou) Co., Ltd.
Investigators
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Study Director: Yingjie Huang, MD Mabspace Biosciences
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Responsible Party: Mabspace Biosciences (Suzhou) Co., Ltd.
ClinicalTrials.gov Identifier: NCT04396821    
Other Study ID Numbers: TST001-1001
First Posted: May 21, 2020    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: May 2020
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