A Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 in Advanced or Metastatic Solid Tumors

  • STATUS
    Recruiting
  • days left to enroll
    88
  • participants needed
    210
  • sponsor
    Mabspace Biosciences (Suzhou) Co., Ltd.
Updated on 30 April 2022

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 but not limited to gastric cancer/gastroesophageal junction adenocarcinoma, pancreas cancer, gallbladder carcinoma, bile duct carcinoma, lung cancer and ovarian carcinoma.

Description

There are two parts in the study. Part I is mono-therapy dose escalation and dose expansion study, and Part II is dose escalation and dose expansion study of combination therapy.

Part I: Mono-therapy dose escalation and dose expansion study:

  1. Mono-therapy dose escalation regimen: The dose escalation study will be conducted using 3+3 dose escalation method at two dosing regimens, i.e."once every 2 weeks (Q2W)"and"once every 3 weeks (Q3W)".
  2. Mono-therapy dose expansion regimen: When the dose level in Q2W group in the mono-therapy dose escalation study is escalated to the MTD/MAD/RP2D, two expansion cohorts will be added at this dose level with about 30 (20-40) subjects with positive CLDN18.2 expression.

Group A: TST001 RP2 DG/GEJ adenocarcinoma with positive CLDN18.2 expression 20-40 Group B: TST001 RP2D Non-G/GEJ adenocarcinoma with positive CLDN18.2 expression 20-40

Part II: Dose escalation and dose expansion study of combination medication

The dose escalation and dose expansion study will be conducted in the following two cohorts:

Group C - first line: TST001+CAPOX Positive CLDN18.2 expression GEJ C 20-40 Group D-second-line +: TST001+paclitaxel Positive CLDN18.2 expression G/GEJ 20-40

The trial will last approximately 3 years from the enrollment to the completion of both Par I and II studies, sample size approximate 165-210 subjects,with assessments including safety labs, ECGs, MUGA scans, PKs and PDs and CT/MRI tumor assessments, based on the Q2W and Q3W dosing schedules.

Details
Condition Advanced Cancer
Treatment TST001 injection
Clinical Study IdentifierNCT04495296
SponsorMabspace Biosciences (Suzhou) Co., Ltd.
Last Modified on30 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

The one who meet all inclusion criteria can be enrolled into the trial
Sign Informed Consent Form voluntarily. Understand the study and be willing to follow and be able to complete all trial procedures
Male or female aged at 18-75 (inclusive) years when ICF is signed
Suffer from advanced unresectable or metastatic malignant local solid tumors confirmed by histological diagnosis and meet the criteria of the enrolled group as follows
Part I: Mono-therapy dose escalation and expansion study
Mono-therapy dose escalation study: The subjects for whom no standard
treatment regimens are available or who is intolerable to standard treatments
Mono-therapy dose expansion study: The subjects with positive CDLN18.2
expression in tumor tissue (which is defined as ≥40% tumor cells showing
CLDN18.2 membrane dye ≥2+ through immunohistochemistry (IHC) test by the
central laboratory) confirmed by the central laboratory at enrollment. There
are 2 groups in Part I as follow
Group A: The subjects with G/GEJ adenocarcinoma for whom no standard therapy
regimens are available currently or who are intolerable to standard therapy
regimens; Group B: The subjects with other malignant tumors (including but not
limited to ductal adenocarcinoma of pancreas, bile duct carcinoma, lung
cancer, ovarian carcinoma and other malignant solid tumors) for whom no
standard therapy regimens are available currently or who are intolerable to
standard therapy regimens; Part II: Dose escalation and expansion study of
combination medication
Dose escalation study of combination medication (dose escalation part)
Group C: The subjects with HER2 negative G/GEJ adenocarcinoma without previous
systemic chemotherapy. The subjects who have completed neoadjuvant
chemotherapy or adjuvant chemotherapy within at least 6 months prior to the
initial dosing of the study are allowed to be enrolled
Group D: The subjects with G/GEJ adenocarcinoma at least with previous first-
line systemic chemotherapy
Dose expansion study of combination medication (dose expansion part)
The subjects with CDLN18.2 positive solid tumors (which is defined as ≥40%
tumor cells showing CLDN18.2 membrane dye≥2+ through immunohistochemistry
(IHC) test by the central laboratory) confirmed by the central laboratory will
be enrolled
Group C: The subjects with HER2 negative G/GEJ adenocarcinoma without previous
systemic chemotherapy. The subjects who have completed neoadjuvant
chemotherapy or adjuvant chemotherapy within at least 6 months prior to the
initial dosing of the study are allowed to be enrolled
Group D: The subjects with G/GEJ adenocarcinoma at least with previous first-
line systemic chemotherapy; During the study, additional groups for the
treatment of other solid tumors might be added according to the available
clinical and pre-clinical study data (the inclusion criteria is to be
determined)
ECOG score 0-1
Expected survival ≥ 3 months
The results of the laboratory examination at screening must meet all the following
criteria
Absolute neutrophil count (ANC) ≥ 1.5×109/L; Absolute count (WBC) ≥ 2.5×109/L
Platelets ≥ 100×109/L; Haemoglobin ≥ 9 g/dL; International normalized ratio (INR) ≤
5 times Upper Limit of Normal (ULN) / or activated partial thromboplastin time
(APTT) ≤ 1.5 times ULN (for the test without anticoagulant); INR ≤ 2.5 times ULN / or
APTT ≤ 2.5 times ULN (for the test with anticoagulant); Total Bilirubin ≤ 1.5 times
ULN; AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for the subjects with hepatic cancer
or metastases to liver); Albumin ≥ 3.0 g/L; Serum creatinine ≤ 1.5 times ULN, or
creatinine clearance rate ≥ 60 ml/min (creatinine clearance rate will be calculated by
Cock-croft-Gault formula)
Male and female of childbearing age should agree to take effective contraception
measures (refer to Appendix 3. Contraception) from signing ICF till 3 months after the
last dose; Blood β-HCG test for women of childbearing age within 70 hours prior to the
initial dosing must be negative
(For dose expansion study only) There must be at least one assessable lesion
conforming to the definition in RECIST v1.1

Exclusion Criteria

The subjects who meet any one of the following criteria cannot participate in the study
The subjects with advanced unresectable or metastatic local G/GEJ adenocarcinoma who
are supposed to be enrolled into the combination therapy group with CAPOX have
previously received systemic chemotherapy. The subjects will be eligible provided that
they have completed neoadjuvant chemotherapy or adjuvant chemotherapy within at least
months prior to the initial dosing of the study; The subjects with advanced
unresectable or metastatic local G/GEJ adenocarcinoma who are supposed to be enrolled
into the combination therapy with paclitaxel have previously received paclitaxel
The subjects who received radiotherapy within 4 weeks prior to the initial dosing of
the investigational drug (the subjects who received local radiotherapy for bone
The subjects who manifest the symptoms of brain or leptomeningeal metastases
metastases treatment with the radiotherapy related AE resolved to ≤ Grade 1 will be
eligible)
The subjects who received other anti-tumor medication or radiotherapy within 4 weeks
prior to the initial dosing of the investigational drug; The medication (such as
Zoledronic Acid) for bone metastases related events will not influence on the
enrollment
The subjects who received major surgery (exclusive of aspiration biopsy) within 8
weeks prior to the initial dosing of the investigational drug, or who are expected to
undergo major surgery, or who are in the conditions such as severe unhealed wound
trauma, ulcer
The subjects who received the treatment with CLDN18.2 monoclonal antibody or
CLDN-18.2CART
The subjects who have previous serious allergic reactions, or are intolerable to the
known component of TST001 or other monoclonal antibodies (including humanized or
chimeric antibodies)
The subjects who are known to have immediate or delayed hypersensitivity to, be
intolerable to or be forbidden from any component of the investigational drugs
The subjects who have previous serious allergic reaction or intolerance to any
component of CAPOX or taxane drugs
The subjects with central nerve system (CNS) metastasis who meets the following
conditions can be enrolled
The subjects with brain metastasis who are naive to any treatment and have no symptom
or who are in progressive free status persisting for at least 8 weeks after treatment
demonstrated by imaging data and do not require hormone or anti epilepsy treatment at
least within 8 weeks
The subjects suffering from body cavity effusion (hydrothorax, ascites and pericardial
effusion) that requires local treatment or repeated drainage and is not well
controlled at the discretion of the investigator
(For dose expansion study only) The subjects suffering from co-existent malignant
tumors. (The following tumor history at 5 years ago that has been cured will not
influence on the enrollment: non-melasma, skin carcinoma, in situ cancer or
non-invasive tumors.)
The adverse reactions caused by previous treatment have not resolved to ≤ Grade 1 as
per CTCAE v5.0 (exclusive of alopecia and anaemia) before the initial dosing of the
investigational drug. If the adverse reaction has no clinical influence, the Sponsor
and investigator will decide whether the subject can be enrolled in the study after
discussion
The subjects who received growth factor, transfusion or other blood products in
treatment of anaemia or decreased platelet within 14 days before screening
The subjects who experienced clinically significant cardiac diseases within 6 months
before the initial dosing of the investigational drug, including
i. Myocardial infarction, ii. Unstable angina pectoris, iii. Cerebrovascular accident
or iv. Other acute and uncontrollable cardiac diseases; Clinically significant
ventricular arrhythmia history (such as persisting ventricular tachycardia
ventricular fibrillation and torsade de pointes); New York Heart Association (NYHA)
Class III or IV congestive cardiac failure; QTc ≥470 (female) or QTc ≥450 (male) or
medical history or family history of congenital long-QT syndrome ; The subjects with
heart rhythm disorders who requires the treatment with antiarrhythmic drugs (The
treatment
subjects who suffer from atrial fibrillation with heart rate controllable more than 1
month before the initial dosing of the investigational drug will be eligible)
The subjects who are known to have dihydropyrimidine dehydrogenase (DPD) deficiency
(Note: DPD deficiency screening should be performed according to local standard.) (The
Except for
screening will be performed only in the subjects receiving CAPOX.)
The subjects who experienced gastric haemorrhage recently or have the risk of gastric
haemorrhage or gastric perforation demonstrated by evidences will be excluded from the
study at the discretion of the investigator. The subjects suffering from obstruction
pyloric and persistent repeated vomiting
The subjects who are known to have > Grade 1 peripheral sensory neuropathy, unless a
lack of deep tendon reflexes is the only neurological abnormality
The subjects suffering from serious or uncontrollable gastro-intestinal tract bleed
The subjects suffering from active infection requiring systemic treatment
The subjects who have HIV infection history or positive HIV viral test
The subjects who are known to have the history of hepatitis C or chronic active
hepatitis B
HBV virus carriers or the subjects with hepatitis B infection that is stable after
medications (HBV-DNA titer should be no more than 1000 copies [cps]/mL or 200 IU/mL)
The subjects with hepatitis C infection that is stable after medications (HCV-RNA test
negative)
The subjects suffering from active autoimmune disorders who required systemic
immunosuppressive therapy within the past 2 years
The subjects who received systemic immunosuppressive therapy including glucocorticoid
within 2 weeks before the initial dosing of the investigational drug; The subjects
will be allowed to use hydrocortisone or similar drugs at physiologically alternative
dose
Pregnant or lactating women
The subject with other conditions (such as psychological, geographic or medical
conditions) that do not allow them to follow the study schedule and follow-up
procedures. Or the subjects who are unsuitable to be enrolled into the study at the
discretion of the investigator
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