Clinical Trials /

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

NCT04396821

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Cholangiocarcinoma
  • Gastric Carcinoma
  • Lung Carcinoma
  • Malignant Solid Tumor
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Trial to Evaluate Safety and Tolerability of TST001 in Advanced or Metastatic Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: TST001-1001
  • NCT ID: NCT04396821

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
TST001Part A Q2W

Purpose

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 NSCL 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 in 5 dose levels. The Q3W cohort will start when the Q2W
      cohort has successfully completed the third dose level, at which time participants will be
      assigned randomly into the cohorts, depending on which has an open slot when the patient
      completes screening. Part A is the dose finding portion of the trial. A different dose may be
      found for each of the two cohorts. 27 to 54 participants will be enrolled.

      Part B of the trial consists of 3 cohorts of approximately 20 participants each. For Part B,
      participants must have CLDN18.2 expressing tumors above (IHC) ≥ 2+ in ≥ 40% tumor cells 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 any cancer except
      gastric and gastroesophageal cancers, dosed every 2 weeks. Cohort 3 is for all cancers, but
      dosed every 3 weeks. Participants will be randomly assigned 1:1 into Cohort 2 and 3. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Part A Q2WExperimentalDosed every 2 weeks IV with TST001, this arm begins first with 1 mg/kg in 3+3 design, then 3 mg/kg, then 10 mg/kg, then 20 mg/kg, finally 30 mg/kg, the maximum dose for this trial
  • TST001
Part A Q3WExperimentalDosed every 3 weeks IV with TST001, starting when the Q2W arm has finished the 10 mg/kg arm without DLT. Starts at 3 mg/kg, then progresses as the 2 mg/kg arm until DLT or 30 mg/kg.
  • TST001
Part B Cohort 1ExperimentalParticipants with gastric or gastroesophageal junction cancers with (IHC) ≥ 2+ in ≥ 40% tumor cells, dosed Q2W IV with the Part A Q2W DLT of TST001, or 30 mg/kg, whichever was arrived at in Part A.
  • TST001
Part B Cohort 2ExperimentalParticipants with anything other than gastric or gastroesophageal junction cancers with (IHC) ≥ 2+ in ≥ 40% tumor cells, dosed Q2W IV with TST001 as above.
  • TST001
Part B Cohort 3ExperimentalParticipants with any kind of advanced or metastatic cancers with (IHC) ≥ 2+ in ≥ 40% tumor cells, dosed Q3W with the Part A Q3W DLT IV or 30 mg/kg with TST001
  • TST001

Eligibility Criteria

        Inclusion Criteria:

          -  1) Male or female ≥ 18 years. 2) Willing and able to provide signed and dated informed
             consent prior to any study-related procedures and willing and able to comply with all
             study procedures.

             3) Patients with histologically or cytologically confirmed, locally advanced or
             metastatic solid tumors.

             4) 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.

             5) CLDN18.2 expression in tumor (Part B only): patients with locally advanced or
             metastatic unresectable GC, GEJ cancer, or other solid tumor include but not limited
             to pancreatic cancer, cholangiocarcinoma, ovarian cancer, and lung cancer. CLDN18.2
             expression is determined by IHC assessed in central lab where expression 2+ membranous
             staining in ≥40% of tumor cells.

             6) Eastern Cooperative Oncology Group Performance Status (ECOG PS): Part A 0~1, Part B
             0~2.

             7) Life expectancy ≥ 3 months. 8) At least one measurable lesion per RECIST 1.1 (Part
             B only). 9) Provide archived tumor tissue samples either formalin fixed paraffin
             embedded block, OR at least 6 (Part A) or 10 (Part B) unstained slides.

             10) Adequate hepatic function as evidenced by meeting all the following requirements:

               -  Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) without liver metastases (or
                  < 3.0 x ULN if liver metastases are present).

               -  Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 2.5 x ULN without
                  liver metastases (or ≤ 5 x ULN if liver metastases are present).

                  11) Estimated creatinine clearance (CrCL) ≥ 30 mL/min (Cockcroft-Gault Equation).

                  12) Adequate hematological function defined as:

               -  Absolute neutrophil count ≥ 1500/µL without growth factor support in the 2 weeks
                  prior to study entry.

               -  Hemoglobin ≥9 g/dL without transfusion in the 4 weeks prior to study entry.

               -  Platelet count ≥100,000/µL without transfusion in the 2 weeks prior to study
                  entry.

                  13) Coagulation tests, defined by the following:

               -  Activated partial thromboplastin time (aPTT) ≤1.5 × ULN.

               -  International normalized ratio (INR) ≤2.0. Exception: INR >2 to ≤3 is acceptable
                  for patients on warfarin anticoagulation or direct oral anticoagulants without
                  active bleeding within 2 weeks prior to the first dose of the investigational
                  drug.

                  14) Recover to Grade 0-1 from adverse events related to prior anti-cancer therapy
                  except alopecia

        Exclusion Criteria:

          -  1) Symptomatic central nervous system metastases. Patients with asymptomatic CNS
             metastases who are radiologically and neurologically stable for at least 4 weeks
             following CNS-directed therapy, and who are on stable or decreasing doses of
             corticosteroids equivalent to ≤10 mg/day are eligible for study entry.

             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; Liver-directed therapy
                  within 8 weeks prior to Cycle 1 Day 1, including but not limited to stereotactic
                  body radiotherapy (SBRT), transarterial chemoembolization (TACE), and
                  radiofrequency ablation (RFA); palliative radiotherapy to a single area of
                  metastasis (not a target lesion) within 2 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, including CVA, TIA, myocardial infarction, or
                  unstable angina, NYHA class III or IV heart failure or uncontrolled arrhythmia
                  within 6 months of study entry.

                  8) QTc ≥470ms at baseline; taking concomitant medications that would prolong the
                  QT interval; or with family history of long QT syndrome 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. Exception: patients
                  who had a solid organ transplant > 5 years ago and are on no immunosuppressive
                  medications should be discussed with the Medical Monitor.

                  11) Active infection requiring intravenous therapy within 2 weeks prior to entry.

                  12) HIV infection with AIDS defining illness; Patients with a CD4+ T cell count >
                  350 cells/µL and no history of an AIDS-defining illness are eligible for entry.

                  13) Active viral (any etiology) hepatitis patients are excluded. Patients with
                  serologic evidence of chronic HBV infection (defined by a positive hepatitis B
                  surface antigen test and a positive anti-hepatitis core antigen antibody test)
                  who have a viral load below the limit quantification (HBV DNA titer < 1000 cps/mL
                  or 200 IU/mL) and are not currently on viral suppressive therapy may be eligible
                  and should be discussed with the Medical Monitor. Patients with a history of HCV
                  infection should have completed curative antiviral treatment and have a viral
                  load below the limit of quantification.

                  14) Women of childbearing potential, defines as all women physiologically capable
                  of becoming pregnant, unless they are using highly effective methods of
                  contraception (Appendix 3) during the intervention period and for 90 days after
                  the last dose of study intervention.

                  15) Men with a partner of childbearing potential who do not consent to use two
                  highly effective methods of birth control (Appendix 3) during treatment and for
                  an additional 90 days after the last administration of investigational drug. A
                  condom is required to be used by vasectomized men as well as during intercourse
                  with a male partner in order to prevent delivery of the drug via seminal fluid.

                  16) Any condition that the investigator or primary physician believes may not be
                  appropriate for participating the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Participant Safety
Time Frame:up to 90 days following last dose
Safety Issue:
Description:Characterization of TST001 safety profile including frequency of adverse events that are related to treatment.

Secondary Outcome Measures

Measure:Area under plasma concentration vs time curve (AUC) for TST001
Time Frame:up to 30 days following last dose
Safety Issue:
Description:changes in AUC over time in participants with TST001
Measure:Peak plasma concentration Cmax) for TST001
Time Frame:up to 30 days following last dose
Safety Issue:
Description:Cmax is the maximum plasma concentration
Measure:Time to maximum observed plasma concentration (Tmax)
Time Frame:up to 30 days following last dose
Safety Issue:
Description:Tmax is the time in hrs/days it takes to reach Cmax after dosing with TST001
Measure:Terminal elimination half life (t1/2)
Time Frame:up to 30 days following last dose
Safety Issue:
Description:Time for the plasma level of TST001 to decrease b y 1/2 during the terminal elimination phase
Measure:Immunogenicity
Time Frame:up to 30 days following last dose
Safety Issue:
Description:by measurement of Incidence of anti-drug antibodies (ADA)
Measure:Objective response rate (ORR)
Time Frame:up to 90 days following last dose
Safety Issue:
Description:as measured by RECIST 1.1
Measure:Duration of Response (DOR)
Time Frame:up to 90 days following last dose
Safety Issue:
Description:duration of response (DOR)
Measure:Clinical Benefit Rate
Time Frame:up to 90 days following last dose
Safety Issue:
Description:(CBR: CR+PR+SD ≥ 18 weeks)
Measure:Progression free survival (PFS)
Time Frame:up to 90 days following last dose
Safety Issue:
Description:as measured by RECIST v1.1

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Mabspace Biosciences (Suzhou) Co., Ltd.

Last Updated

May 15, 2020