Neoplasms

Digestive System Diseases

All Conditions

Rare Diseases

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Biliary Tract Cancer

Drug: TST001 IV infusion every 3 weeks until disease progression or other discontinuation criteria.

TST001 IV infusion every 3 weeks until disease progression or other discontinuation criteria.

TST001

Jia Fan

TST001 is a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody. This is an open-label, single-arm phase II study to evaluate the efficacy and safety of TST001 for patients with CLDN18.2 positive previously treated unresectable advanced or metastatic Biliary Tract Cancer.

TST001 is a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody. Claudin18.2 (CLDN18.2) protein is one of the family of tetraspanning proteins expressed at epithelial tight junctions and primarily expressed only in normal gastric tissues . CLDN18.2 protein is a pancancer target expressed in primary lesions and metastases of variouscancer types, including gastric cancer, biliary tract cancer and others. Current available information indicates that CLDN18.2 is a promising therapeutic target for the treatment of solid tumors.

This is an open-label, single-arm phase II study to evaluate the efficacy and safety of TST001 for patients with CLDN18.2 positive previously treated unresectable advanced or metastatic Biliary Tract Cancer. Eligible patients will be treated with TST001 until disease progression or other discontinuation criteria met. If there is ≥ one objective response among the first 15 enrolled patients, then the trial continues to enroll a total of 40 patients; if not, then the trial discontinues.

TST001 in Patients With CLDN18.2 Positive Previously Treated Advanced Biliary Tract Cancer

An Open-label, Single-arm Phase II Study to Evaluate the Efficacy and Safety of TST001 for Patients With CLDN18.2 Positive Previously Treated Unresectable Advanced or Metastatic Biliary Tract Cancer

ORR according to RECIST 1.1 using investigator assessment

PFS accorridng RECSIST1.1 using investigator assessment

Time from enrollment to death of any cause

DoR accroding to RECSIST1.1 using investigator assessment

Patients who were assessed as partial response, complete response or stable disease

Adverse events will be graded according to NCI-CTC AE v5.0

Transcenta Holding Limited

Shanghai Zhongshan Hospital

All Drugs and Chemicals

Antineoplastic Agents

Gastrointestinal Agents

Antibodies

Antibodies, Monoclonal

Gemcitabine

Capecitabine

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Nivolumab

Oxaliplatin

Immunoglobulins

Pancrelipase

Pancreatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Dosed every 2 weeks IV with TST001, multiple dose levels will be tested.

Dosed every 3 weeks IV with TST001, multiple dose levels will be tested.

Participants with gastric or gastroesophageal junction cancers and CLDN18.2 expression

Participants with ductal adenocarcinoma of pancreas and CLDN18.2 expression and CLDN18.2 expression

Participants with advanced or metastatic solid tumors other than G/GEJ adenocarcinoma and CLDN18.2 expression

Participants with HER2 negative or unknown locally advanced or metastatic G/GEJ adenocarcinoma

Participants with locally advanced or metastatic G/GEJ adenocarcinoma

Participants with locally advanced or metastatic biliary tract cancer

TST001 will be administered by specified doses on specified day

Oxaliplatin will be administered by specified doses on specified day

Capecitabine will be administered by specified doses on specified day

Paclitaxel will be administered by specified doses on specified day

Gemcitabine will be administered by specified doses on specified day

Cisplatin will be administered by specified doses on specified days Oxaliplatin will be administered by specified doses on specified day Drug: Capecitabine Capecitabine will be administered by specified doses on specified day

Nivolumab will be administered by specified doses on specified day

Qian Wu

Henry Mao

Fuyou Zhao

lin Shen

Bangwei Cao

Lin Zhao

Jun Liang

Jun Zhang

Zengqing Guo

Chunmei Shi

Jiayi Li

Yanhong Deng

Kehe Chen

Lin Wang

Qingxia Fan

Yuxian Bai

Ning li

Huiting Xu

Fuxiang Zhou

Xianli Yin

Shan Zeng

Feng Guo

Zhixiang Zhuang

Liang Han

Hua Wang

Ying Cheng

Wei Li

Zhitu Zhu

Jingdong Zhang

Xiujuan Qu

Meili Sun

Jianhua Shi

Xiaochun Zhang

guo weijian

Tianshu Liu

Dan Cao

Jin Lu

Hongli Li

Diansheng Zhong

nong xu

Ying Yuan

Haijun Zhong

This is an open-label, multi-center, Phase I trial of TST001. Subjects with locally advanced or metastatic solid tumors will be enrolled. The study will consist of two parts: Part A is dose escalation and dose expansion phase for mono-therapy, and Part B is dose escalation and dose expansion phase for combination therapy in gastric, gastroesophageal junction(G/GEJ) and biliary tract cancer, etc.

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.

The dose escalation study will be conducted utilizing 3+3 design with two dosing regimens, i.e. "once every 2 weeks (Q2W)" and "once every 3 weeks (Q3W)".

After MTD/RP2D determined, three cohorts may be included in the expansion plan, with about 30 (20-40) subjects with positive CLDN18.2 expression be treated in each cohort, as shown below (during the study, the treatment cohorts may be adjusted or added based on the clinical and pre-clinical study data).

Approximately 320-540 treated subjects in total

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

A Phase I/IIa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 - Claudin18.2 Monoclonal Antibody in the Treatment of Locally Advanced or Metastatic Solid Tumors

An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

The maximum tolerated dose (MTD) is commonly estimated to be the maximum dose that can be determined through DLT of two among 6 subjects administered with TST001 Q2W in 28 days cycles.

The maximum tolerated dose (MTD) is commonly estimated to be the maximum dose that can be determined through DLT of two among 6 subjects administered with TST001 once every 3 weeks in 21 days cycles.

The RP2D will be determined during the dose expansion stage of the study. RP2D will be determined using available safety and efficacy data.

DLT is short for Dose Limiting Toxicity. dose-limiting describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.

Characterization of TST001 + CAPOX safety profile including frequency and severity of adverse events that are related to treatment.

Changes in AUC over time in participants with TST001.

Cmax is the maximum plasma concentration.

Tmax is the time in hrs/days it takes to reach Cmax after dosing with TST001

Time for the plasma level of TST001 to decrease b y 1/2 during the terminal elimination phase.

by measurement of Incidence of anti-drug antibodies (ADA)

DOR is defined as the time from the date of the first response CR (complete remission)/PR (partial remission) (whichever is first recorded) to the date of radiographical progression/death or date of censoring.

Bristol-Myers Squibb

Suzhou Transcenta Therapeutics Co., Ltd.

Gland and Hormone Related Diseases

Stomach Neoplasms

Pancreatic Neoplasms

Stomach Cancer

Pancreatic Cancer

Micronutrients

Hematinics

Bone Density Conservation Agents

Vitamins

Leucovorin

Fluorouracil

Levoleucovorin

Calcium

Folic Acid

Calcium, Dietary

Folinic Acid

Folate

Vitamin B9

Dosed every 2 weeks IV with TST001, starting dose is 1 mg/kg, multiple dose levels will be tested.

Dosed every 3 weeks IV with TST001, starting dose is 3 mg/kg, and multiple dose levels will be tested.

Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ adenocarcinoma.

Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies.

Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma.

TST001 is a humanized IgG1 monoclonal antibody.

Nivolumab is one of the PD-1 checkpoint inhibitors, and has proved clinical benefit for multiple late-stage malignancies

Nivolumab Injection [Opdivo]

mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin.

mFOLFOX6

Angela Ireland, MS

Caroline Germa, MD

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.

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.

Part A - 2 arms, Q2w and Q3w, 3+3 design dose escalation; Part B - dose expansion, 3 Cohorts

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

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

As described below. Patient personal data will be kept confidential as per HIPAA.

Characterization of TST001 safety profile including frequency and severity of adverse events that are related to treatment.

As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort

Characterization of TST001 + Nivolumab safety profile including frequency and severity of adverse events that are related to treatment.

Characterization of TST001 + Nivolumab + mFOLFOX6 safety profile including frequency and severity of adverse events that are related to treatment.

Characterization of TST001 + Gemcitabine + albumin-bound paclitaxel safety profile including frequency and severity of adverse events that are related to treatment.

time to reach maximum serum concentration (Tmax)

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Amino Acids

Tin Fluorides

Antibodies, Bispecific

Complement System Proteins

Mitogens

Tyrosine Kinase Inhibitors

Tyrosine

Initial treatment (4-6 cycles): IBI315 injection, oxaliplatin, capecitabine

* IBI315: 1200 mg per cycle d1 dosing, intravenous drip, 3 weeks as one treatment cycle.
* Oxaliplatin: 130 mg/m2, d1 per cycle, intravenous drip, 3 weeks as a treatment cycle.
* Capecitabine: 1000 mg/m2 orally twice daily (1 dose in the morning and 1 dose in the evening), d1-d14 per cycle, 2 weeks off 1 week, 3 weeks cycle.

Patients with CR/PR/SD enter maintenance therapy: IBI315 monotherapy maintenance

- IBI315: 1200 mg IV drip per cycle d1 for 3 weeks.

Initial treatment (4-6 cycles): PD-L1 monoclonal antibody, TST001 injection, oxaliplatin, capecitabine

* TST001: 3mg, 4.5mg and 6mg dose levels for hill climbing trial, dose per cycle d1, IV drip, 3 weeks for one treatment cycle. 3-6 patients were enrolled in each dose level (3 patients were enrolled if no DLT was present, if present extended to 6 patients)
* TQB2450 injection: 1200 mg per cycle d1 dosing, IV drip, 3 weeks as a treatment cycle.
* Oxaliplatin: 130 mg/m2 per cycle d1 dosing, intravenous drip, 3 weeks as a treatment cycle.
* Capecitabine: 1000 mg/m2 orally twice daily (1 dose in the morning and 1 dose in the evening), d1-d14 per cycle, 2 weeks off 1 week, 3 weeks cycle.

Patients with CR/PR/SD enter maintenance therapy: TQB2450 injection + TST001

* TST001: maintenance at the dose level used (3mg/4.5mg/6mg), dosed d1 per cycle, IV drip, 3 weeks as a treatment cycle.
* TQB2450 injection: 1200mg, dosed d1 per cycle, intravenous drip, 3 weeks as a treatment cycle.

Initial treatment (4-6 cycles): TQB2450 injection, Anrotinib, Oxaliplatin, Capecitabine

* TQB2450 injection: 1200mg per cycle d1 dosing, intravenous drip, 3 weeks as a treatment cycle.
* Anrotinib: 1 capsule (10 mg) once daily, dosed every cycle d1-d14, stopping for 2 consecutive weeks, 3 weeks as a treatment cycle
* Oxaliplatin: 130 mg/m2, d1 per cycle, intravenous drip, 3-week treatment cycle.
* Capecitabine: 1000 mg/m2 orally twice daily (1 dose in the morning and 1 dose in the evening), d1-d14 per cycle, 2 weeks off 1 week, 3 weeks as a treatment cycle.

Patients with CR/PR/SD enter maintenance therapy: PD-L1 inhibitor, anlotinib

* PD-L1 monoclonal antibody (TQB2450): 1200 mg d1 per cycle, intravenous drip, 3 weeks as a treatment cycle.
* Anlotinib: 1 capsule (10mg) once daily, d1-d14 per cycle, stopping for 2 weeks, 3 weeks as a treatment cycle.

IBI315 is a recombinant fully humanized anti-programmed death receptor 1 (PD-1) and humanized anti-human epidermal growth factor receptor 2 (HER2) bispecific antibody injection.

IBI315

Oxaliplatin is a type of chemotherapy. It is used as a treatment for different types of cancer, including gastric cancer.

Capecitabine is a type of chemotherapy. It is used as a treatment for different types of cancer, including gastric cancer.

TST001 is a high-affinity humanized monoclonal antibody targeting Claudin 18.2 with enhanced antibody-dependent cytotoxic (ADCC) and complement-dependent cytotoxic (CDC) activity, showing potent antitumor activity in xenograft assays.

TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.

TQB2450

Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling.

Anrotinib

Abstract Study title: Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes Protocol No: GC-MATCH Initiator: Henan Cancer Hospital Nature of study Investigator-initiated exploratory study Subjects Advanced first-line gastric cancer or adenocarcinoma of the gastroesophageal junction Objective: To evaluate the efficacy and safety of different first-line treatment options for unresectable locally advanced/advanced gastric or combined gastroesophageal adenocarcinoma with different gene/protein types.

Evaluation criteria: To evaluate the adverse effects of drugs using the NCI CTCAE V5.0 criteria.

RECIST1.1 criteria were used to evaluate drug efficacy Study endpoints: Primary indicators Objective Response Rate (ORR) Secondary indicators 1. drug safety. 2. disease control rate DCR (CR+PR+SD). 3. duration of remission DoR. 4. disease-free survival (PFS) and overall survival time (OS). 5. R0/R1 surgical resection rate Study design: Single-center umbrella clinical trial Planned number of enrollment: Total 39-45 cases Sample size estimation: This is an exploratory study and sample size was not calculated Statistical methods: Selection of data for statistical analysis Full Analysis Set (FAS): The efficacy analysis was performed on all patients who were enrolled and used the drug at least once, according to the principle of intentional analysis (ITT).

Per-protocol Set: Cases with at least one oncologic efficacy assessment, compliance with the trial protocol, good compliance, no prohibited drugs during the trial, and completion of the case report form.

Safety Analysis Set: All patients who had used the trial drug at least once and had a safety record after the drug was administered were enrolled in the Safety Analysis Set.

Statistical analysis plan Validity analysis: for the efficacy index PFS, the Kaplan-Meier method will be used to estimate its median time and column Statistical methods: Out of two-sided 95% confidence intervals. Disease control rate (DCR = CR+PR+SD) and objective remission rate (ORR = CR+PR) were calculated using Fisher exact probability and bilateral 95% confidence intervals were presented.

Safety analysis: descriptive statistical analysis was used to tabulate the AEs that occurred in this trial. laboratory test results were described as normal before the trial but abnormal after treatment and in relation to the trial drug when abnormal changes occurred.

Treatment protocol:

All subjects in this study were first tested for genes/proteins (HER2 protein, HER2FISH, PD-L1 protein 22C3, Claudin18.2, MMR) and received treatment in different groups according to gene/protein expression.

Group 1 HER protein positive 3+ or FISH amplification or HER protein 2+ but FISH amplification Initial treatment (4-6 cycles): IBI315 injection, oxaliplatin, capecitabine Group 2 Claudin18.2 protein-positive Initial treatment (4-6 cycles): PD-L1 monoclonal antibody, TST001 injection, oxaliplatin, capecitabine Group 3 Her protein and Claudin18.2 protein were negative Initial treatment (4-6 cycles): TQB2450 injection, Anrotinib, Oxaliplatin, Capecitabine Patients can undergo radical gastric cancer surgery or radical gastric cancer surgery + local treatment during the maintenance treatment phase if their condition is stable and after in-hospital MDT consultation. The duration of maintenance treatment was 2 years from the time of enrollment.

Principal Investigator: Luo Suxia, Li Ning Group leader unit: Henan Cancer Hospital

Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes

An adverse event contains multiple severity grades, typically the start date is the date of mild (grade 1) occurrence, the end date is the date of improvement, and the level is filled in at the highest level.

The remission period is usually defined as the period from the onset of efficacy until the confirmation of tumor progression. The objective remission rate is generally defined as the sum of complete remission plus partial remission (CR+PR).

Time from when the patient first achieved complete remission or partial remission to disease progression.

Time from randomization grouping of patients to disease progression or death from any cause.

From date of randomization until the date of death from any cause, assessed up to 100 months

Proportion of patients who achieve complete remission, partial remission, or disease control with optimal efficacy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TST001 in Patients With CLDN18.2 Positive Previously Treated Advanced Biliary Tract Cancer	NCT05190575	Biliary Tract N...	TST001	18 Years -	Shanghai Zhongshan Hospital
A Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 in Advanced or Metastatic Solid Tumors	NCT04495296	Advanced Cancer	TST001 Oxaliplatin Capecitabine Paclitaxel Gemcitabine Cisplatin Nivolumab	18 Years -	Suzhou Transcenta Therapeutics Co., Ltd.
A Trial to Evaluate Safety and Tolerability of TST001 in Advanced or Metastatic Solid Tumors	NCT04396821	Advanced Cancer Gastric Cancer Gastroesophagea... Pancreatic Canc...	TST001 Nivolumab Injec... mFOLFOX6 Gemcitabine Albumin-Bound P...	18 Years -	Suzhou Transcenta Therapeutics Co., Ltd.
TST001 in Patients With CLDN18.2 Positive Previously Treated Advanced Biliary Tract Cancer	NCT05190575	Biliary Tract N...	TST001	18 Years -	Shanghai Zhongshan Hospital
A Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 in Advanced or Metastatic Solid Tumors	NCT04495296	Advanced Cancer	TST001 Oxaliplatin Capecitabine Paclitaxel Gemcitabine Cisplatin Nivolumab	18 Years -	Suzhou Transcenta Therapeutics Co., Ltd.
TST001 in Patients With CLDN18.2 Positive Previously Treated Advanced Biliary Tract Cancer	NCT05190575	Biliary Tract N...	TST001	18 Years -	Shanghai Zhongshan Hospital
Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes	NCT05608785	Gastric Cancer Gastroesophagea...	IBI315 Oxaliplatin Capecitabine TST001 TQB2450 Anrotinib	18 Years - 75 Years	Henan Cancer Hospital
Single-center, Multi-cohort Exploratory Phase Ib/II Clinical Study of First-line Treatment of Unresectable Locally Advanced/Advanced Adenocarcinoma of the Stomach or Gastroesophageal Junction Based on Different Genotypes	NCT05608785	Gastric Cancer Gastroesophagea...	IBI315 Oxaliplatin Capecitabine TST001 TQB2450 Anrotinib	18 Years - 75 Years	Henan Cancer Hospital

Spots Global Cancer Trial Database for tst001

Every month we try and update this database with for tst001 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for tst001

Every month we try and update this database with for tst001 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for tst001 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.