Et forsøk for å evaluere sikkerhet og tolerabilitet av TST001 i avanserte eller metastatiske solide svulster
En fase I/IIa klinisk studie for å evaluere sikkerheten, tolerabiliteten og farmakokinetikken til TST001 administrert som monoterapi eller i kombinasjon med Nivolumab hos pasienter med lokalt avanserte eller metastatiske solide svulster
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.
Studieoversikt
Status
Detaljert 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.
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiesteder
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Arizona
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Gilbert, Arizona, Forente stater, 85234
- Banner MD Anderson
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Tucson, Arizona, Forente stater, 85724
- University of Arizona
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Connecticut
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New Haven, Connecticut, Forente stater, 06519
- Yale University
-
-
Florida
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Sarasota, Florida, Forente stater, 34232
- Florida Cancer Specialists
-
-
Georgia
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Atlanta, Georgia, Forente stater, 30033
- Emory University
-
-
Kansas
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Kansas City, Kansas, Forente stater, 66160
- University of Kansas, School of Medicine
-
-
Missouri
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St Louis, Missouri, Forente stater, 63110
- Washington University
-
-
New York
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New York, New York, Forente stater, 10065
- Memorial Sloan Kettering
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Stony Brook, New York, Forente stater, 11794
- Stony Brook Cancer Center
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-
North Carolina
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Winston-Salem, North Carolina, Forente stater, 27157
- Wake Forest Baptist Comprehensive Cancer Center
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-
Ohio
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Canton, Ohio, Forente stater, 44718
- Gabrail Cancer Research
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Pennsylvania
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Gettysburg, Pennsylvania, Forente stater, 17325
- Pennsylvania Cancer Specialist Research Institute
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Pittsburgh, Pennsylvania, Forente stater, 15212
- Allegheny Hospital
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Tennessee
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Nashville, Tennessee, Forente stater, 37203
- Sarah Cannon Research Institute
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Nashville, Tennessee, Forente stater, 37232
- Vanderbilt University
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Texas
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Austin, Texas, Forente stater, 78704
- NEXT Oncology
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Washington
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Seattle, Washington, Forente stater, 98104
- Swedish Cancer Institute
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Wisconsin
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Milwaukee, Wisconsin, Forente stater, 53226
- Medical College of Wisconsin
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
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 studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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. |
|
Eksperimentell: 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. |
|
Eksperimentell: 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. |
|
Eksperimentell: 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 |
|
Eksperimentell: 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 navn:
Chemotherapy medication |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
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 |
Tiltaksbeskrivelse |
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
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Studieleder: Charlie Qi, MD, Suzhou Transcenta Therapeutics Co.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Sykdommer i det endokrine systemet
- Neoplasmer etter nettsted
- Neoplasmer
- Gastrointestinale neoplasmer
- Neoplasmer i fordøyelsessystemet
- Sykdommer i fordøyelsessystemet
- Gastrointestinale sykdommer
- Magesykdommer
- Neoplasmer i endokrine kjertel
- Pankreassykdommer
- Neoplasmer i magen
- Neoplasmer i bukspyttkjertelen
- Aminosyrer, peptider og proteiner
- Proteiner
- Organiske kjemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Hydrokarboner
- Cycloparaffins
- Hydrokarboner, alicyklisk
- Hydrokarboner, syklisk
- Terpener
- Antistoffer, monoklonalt, humanisert
- Antistoffer, monoklonalt
- Antistoffer
- Immunoglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Taxoider
- Cyclodecanes
- Diterpenes
- Deoxycytidine
- Cytidin
- Pyrimidin -nukleosider
- Pyrimidiner
- Albuminer
- Paclitaxel
- Nivolumab
- Albuminbundet paklitaksel
- Gemcitabin
Andre studie-ID-numre
- TST001-1001
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (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.
Tilgangskriterier for IPD-deling
Be an active investigator in the TST001-1001 trial
IPD-deling Støtteinformasjonstype
- STUDY_PROTOCOL
- CSR
Legemiddel- og utstyrsinformasjon, studiedokumenter
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