Et forsøg for at evaluere sikkerhed og tolerabilitet af TST001 i avancerede eller metastatiske solide tumorer
Et fase I/IIa klinisk forsøg til evaluering af sikkerhed, tolerabilitet og farmakokinetik af TST001 administreret som monoterapi eller i kombination med nivolumab hos patienter med lokalt avancerede eller metastatiske solide tumorer
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.
Studieoversigt
Status
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiesteder
-
-
Arizona
-
Gilbert, Arizona, Forenede Stater, 85234
- Banner MD Anderson
-
Tucson, Arizona, Forenede Stater, 85724
- University of Arizona
-
-
Connecticut
-
New Haven, Connecticut, Forenede Stater, 06519
- Yale University
-
-
Florida
-
Sarasota, Florida, Forenede Stater, 34232
- Florida Cancer Specialists
-
-
Georgia
-
Atlanta, Georgia, Forenede Stater, 30033
- Emory University
-
-
Kansas
-
Kansas City, Kansas, Forenede Stater, 66160
- University of Kansas, School of Medicine
-
-
Missouri
-
St Louis, Missouri, Forenede Stater, 63110
- Washington University
-
-
New York
-
New York, New York, Forenede Stater, 10065
- Memorial Sloan Kettering
-
Stony Brook, New York, Forenede Stater, 11794
- Stony Brook Cancer Center
-
-
North Carolina
-
Winston-Salem, North Carolina, Forenede Stater, 27157
- Wake Forest Baptist Comprehensive Cancer Center
-
-
Ohio
-
Canton, Ohio, Forenede Stater, 44718
- Gabrail Cancer Research
-
-
Pennsylvania
-
Gettysburg, Pennsylvania, Forenede Stater, 17325
- Pennsylvania Cancer Specialist Research Institute
-
Pittsburgh, Pennsylvania, Forenede Stater, 15212
- Allegheny Hospital
-
-
Tennessee
-
Nashville, Tennessee, Forenede Stater, 37203
- Sarah Cannon Research Institute
-
Nashville, Tennessee, Forenede Stater, 37232
- Vanderbilt University
-
-
Texas
-
Austin, Texas, Forenede Stater, 78704
- NEXT Oncology
-
-
Washington
-
Seattle, Washington, Forenede Stater, 98104
- Swedish Cancer Institute
-
-
Wisconsin
-
Milwaukee, Wisconsin, Forenede Stater, 53226
- Medical College of Wisconsin
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: 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. |
|
Eksperimentel: 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. |
|
Eksperimentel: 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. |
|
Eksperimentel: 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 |
|
Eksperimentel: 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
Andre navne:
Chemotherapy medication |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Participant Safety as characterized by frequency and severity of adverse events
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Immunogenicity
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
Tidsramme: Up to 30 days following last dose
|
Maximum serum concentration (Cmax) |
Up to 30 days following last dose
|
|
PK
Tidsramme: Up to 30 days following last dose
|
time to reach maximum serum concentration (Tmax) |
Up to 30 days following last dose
|
|
PK
Tidsramme: Up to 30 days following last dose
|
Area Under the Curve |
Up to 30 days following last dose
|
Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Studieleder: Charlie Qi, MD, Suzhou Transcenta Therapeutics Co.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Sygdomme i det endokrine system
- Neoplasmer efter sted
- Neoplasmer
- Gastrointestinale neoplasmer
- Neoplasmer i fordøjelsessystemet
- Sygdomme i fordøjelsessystemet
- Gastrointestinale sygdomme
- Mavesygdomme
- Neoplasmer i endokrine kirtler
- Pancreassygdomme
- Neoplasmer i maven
- Bugspytkirtel neoplasmer
- Aminosyrer, peptider og proteiner
- Proteiner
- Organiske kemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Kulbrinter
- Cycloparaffiner
- Kulbrinter, alicyklisk
- Kulbrinter, cyklisk
- Terpenes
- Antistoffer, monoklonal, humaniseret
- Antistoffer, monoklonal
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serum globuliner
- Globuliner
- Taxoider
- Cyclodecanes
- Diterpenes
- Deoxycytidin
- Cytidin
- Pyrimidin -nukleosider
- Pyrimidiner
- Albuminer
- Paclitaxel
- Nivolumab
- Albumin-bundet Paclitaxel
- Gemcitabin
Andre undersøgelses-id-numre
- TST001-1001
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
As described below. Patient personal data will be kept confidential as per HIPAA.
IPD-delingstidsramme
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.
IPD-delingsadgangskriterier
Be an active investigator in the TST001-1001 trial
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- CSR
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .