Una prova per valutare la sicurezza e la tollerabilità di TST001 nei tumori solidi avanzati o metastatici
Uno studio clinico di fase I/IIa per valutare la sicurezza, la tollerabilità e la farmacocinetica di TST001 somministrato in monoterapia o in combinazione con nivolumab in pazienti con tumori solidi localmente avanzati o metastatici
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.
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Luoghi di studio
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Arizona
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Gilbert, Arizona, Stati Uniti, 85234
- Banner MD Anderson
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Tucson, Arizona, Stati Uniti, 85724
- University of Arizona
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Connecticut
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New Haven, Connecticut, Stati Uniti, 06519
- Yale University
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Florida
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Sarasota, Florida, Stati Uniti, 34232
- Florida Cancer Specialists
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Georgia
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Atlanta, Georgia, Stati Uniti, 30033
- Emory University
-
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Kansas
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Kansas City, Kansas, Stati Uniti, 66160
- University of Kansas, School of Medicine
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Missouri
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St Louis, Missouri, Stati Uniti, 63110
- Washington University
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New York
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New York, New York, Stati Uniti, 10065
- Memorial Sloan Kettering
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Stony Brook, New York, Stati Uniti, 11794
- Stony Brook Cancer Center
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North Carolina
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Winston-Salem, North Carolina, Stati Uniti, 27157
- Wake Forest Baptist Comprehensive Cancer Center
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Ohio
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Canton, Ohio, Stati Uniti, 44718
- Gabrail Cancer Research
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Pennsylvania
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Gettysburg, Pennsylvania, Stati Uniti, 17325
- Pennsylvania Cancer Specialist Research Institute
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Pittsburgh, Pennsylvania, Stati Uniti, 15212
- Allegheny Hospital
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Tennessee
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Nashville, Tennessee, Stati Uniti, 37203
- Sarah Cannon Research Institute
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Nashville, Tennessee, Stati Uniti, 37232
- Vanderbilt University
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Texas
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Austin, Texas, Stati Uniti, 78704
- NEXT Oncology
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Washington
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Seattle, Washington, Stati Uniti, 98104
- Swedish Cancer Institute
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Wisconsin
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Milwaukee, Wisconsin, Stati Uniti, 53226
- Medical College of Wisconsin
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-
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Part A Q2W
Dosed every 2 weeks IV with TST001, starting dose is 1 mg/kg, multiple dose levels will be tested. |
TST001 is a humanized IgG1 monoclonal antibody. |
|
Sperimentale: Part A Q3W
Dosed every 3 weeks IV with TST001, starting dose is 3 mg/kg, and multiple dose levels will be tested. |
TST001 is a humanized IgG1 monoclonal antibody. |
|
Sperimentale: Part B Cohort A
Patients with previously untreated, unresectable, locally advanced or metastatic GC/GEJ 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 mFOLFOX6 is a combination chemotherapy regimen including the drugs leucovorin calcium (folinic acid), fluorouracil, and oxaliplatin. |
|
Sperimentale: Part B Cohort B
Patients with GC/GEJ adenocarcinoma who have radiologically progressed following one or two prior systemic therapies. |
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 |
|
Sperimentale: Part B Cohort C
Patients with previously untreated, unresectable, locally advanced or metastatic histologically confirmed pancreatic adenocarcinoma. |
TST001 is a humanized IgG1 monoclonal antibody. Chemotherapy medication
Altri nomi:
Chemotherapy medication |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Participant Safety as characterized by frequency and severity of adverse events
Lasso di tempo: up to 100 days following last dose
|
Characterization of TST001 safety profile including frequency and severity of adverse events that are related to treatment. |
up to 100 days following last dose
|
|
Maximum Tolerated Dose (MTD or Recommended Phase 2 Dose (RP2D)
Lasso di tempo: up to 100 days following last dose
|
As measured by number of participants experiencing dose related toxicity (DLT) in each escalating cohort |
up to 100 days following last dose
|
|
Participant Safety and Tolerability of TST001 in combination with Nivolumab as characterized by frequency and severity of adverse events
Lasso di tempo: 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. |
Up to 100 days following last dose
|
|
Participant Safety and Tolerability of TST001 in combination with Nivolumab and mFOLFOX6 as characterized by frequency and severity of adverse events
Lasso di tempo: 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. |
Up to 100 days following last dose
|
|
Participant Safety and Tolerability of TST001 in combination with gemcitabine and albumin-bound paclitaxel as characterized by frequency and severity of adverse events
Lasso di tempo: 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. |
Up to 100 days following last dose
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Immunogenicity
Lasso di tempo: up to 30 days following last dose
|
by measurement of Incidence of anti-drug antibodies (ADA) |
up to 30 days following last dose
|
|
Objective response rate (ORR)
Lasso di tempo: up to 24 months, until disease progression or start of another anti-cancer therapy
|
as measured by RECIST 1.1 |
up to 24 months, until disease progression or start of another anti-cancer therapy
|
|
Duration of Response (DOR)
Lasso di tempo: up to 24 months, until disease progression or start of another anti-cancer therapy
|
duration of response (DOR) |
up to 24 months, until disease progression or start of another anti-cancer therapy
|
|
Progression free survival (PFS)
Lasso di tempo: up to 24 months, until disease progression or start of another anti-cancer therapy
|
as measured by RECIST v1.1 |
up to 24 months, until disease progression or start of another anti-cancer therapy
|
|
PK parameters
Lasso di tempo: Up to 30 days following last dose
|
Maximum serum concentration (Cmax) |
Up to 30 days following last dose
|
|
PK
Lasso di tempo: Up to 30 days following last dose
|
time to reach maximum serum concentration (Tmax) |
Up to 30 days following last dose
|
|
PK
Lasso di tempo: Up to 30 days following last dose
|
Area Under the Curve |
Up to 30 days following last dose
|
Collaboratori e investigatori
Collaboratori
Investigatori
- Direttore dello studio: Charlie Qi, MD, Suzhou Transcenta Therapeutics Co.
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Malattie del sistema endocrino
- Neoplasie per sede
- Neoplasie
- Neoplasie gastrointestinali
- Neoplasie dell'apparato digerente
- Malattie dell'apparato digerente
- Malattie gastrointestinali
- Malattie dello stomaco
- Neoplasie delle ghiandole endocrine
- Malattie pancreatiche
- Neoplasie allo stomaco
- Neoplasie pancreatiche
- Aminoacidi, peptidi e proteine
- Proteine
- Prodotti chimici organici
- Composti eterociclici, 1-anello
- Composti eterociclici
- Idrocarburi
- Cicloparaffins
- Idrocarburi, aliciclici
- Idrocarburi, ciclici
- Terpeni
- Anticorpi, monoclonali, umanizzati
- Anticorpi, monoclonali
- Anticorpi
- Immunoglobuline
- Immunoproteine
- Proteine del sangue
- Globuline sieriche
- Globuline
- Taxoidi
- Ciclodecani
- Diterpenes
- Deossictidina
- Citidina
- Nucleosidi di pirimidina
- Pirimidine
- Albumine
- Paclitaxel
- Nivolumab
- Paclitaxel legato all'albumina
- Gemcitabina
Altri numeri di identificazione dello studio
- TST001-1001
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
Descrizione del piano IPD
As described below. Patient personal data will be kept confidential as per HIPAA.
Periodo di condivisione IPD
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.
Criteri di accesso alla condivisione IPD
Be an active investigator in the TST001-1001 trial
Tipo di informazioni di supporto alla condivisione IPD
- STUDIO_PROTOCOLLO
- RSI
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .