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A Study of ARRY-382 in Combination With Pembrolizumab for the Treatment of Patients With Advanced Solid Tumors

21. maj 2022 opdateret af: Pfizer

A Phase 1b/2 Study of ARRY-382 in Combination With Pembrolizumab, a Programmed Cell Death Receptor 1 (PD-1) Antibody, for the Treatment of Patients With Advanced Solid Tumors

This is an open-label, multicenter Phase 1b/2 study to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ARRY-382 in combination with pembrolizumab in adult patients with selected advanced solid tumors (Part A/Phase 1b); and to estimate the efficacy of the combination in three separate cohorts: 1) patients with advanced solid tumors that have progressed on prior PD-1/PD-L1inhibitors, 2) patients with platinum-resistant ovarian cancer and 3) patients with pancreatic ductal adenocarcinoma (Phase 2).

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

ARRY-382 is an inhibitor of CSF1R (colony-stimulating factor-1 receptor).

Each phase of the study consists of a 28-day screening period; 21-day treatment cycles with the combination of ARRY-382 and pembrolizumab until disease progression as determined by the Investigator, unacceptable toxicity, withdrawal of consent, or death (or other discontinuation criteria are met), and a 30-day safety follow-up period. Patients in all cohorts/phases will be monitored for overall survival (OS) until 1 year after the date of the last patient's first visit.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

82

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater, 90095
        • Ronald Reagan UCLA Medical Center
      • Los Angeles, California, Forenede Stater, 90095
        • UCLA Hematology/Oncology
      • Santa Monica, California, Forenede Stater, 90404
        • UCLA Hematology/Oncology - Santa Monica
    • Colorado
      • Aurora, Colorado, Forenede Stater, 80045
        • University of Colorado Denver
      • Aurora, Colorado, Forenede Stater, 80045
        • University of Colorado Hospital
    • Florida
      • Port Saint Lucie, Florida, Forenede Stater, 34952
        • Hem-Onc Associates of Treasure Coast
    • Indiana
      • Fort Wayne, Indiana, Forenede Stater, 46845
        • Parkview Regional Medical Center
      • Fort Wayne, Indiana, Forenede Stater, 46845
        • Parkview Cancer Institute
      • Fort Wayne, Indiana, Forenede Stater, 46845
        • Parkview Research Center
      • Fort Wayne, Indiana, Forenede Stater, 46845
        • PPG
      • Lafayette, Indiana, Forenede Stater, 47905
        • Horizon Oncology Research, Inc.
    • Iowa
      • Cedar Rapids, Iowa, Forenede Stater, 52403
        • Hall-Perrine Cancer Center Laboratory
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, Forenede Stater, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, Forenede Stater, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, Forenede Stater, 02215
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48201
        • Karmanos Cancer Institute
    • Minnesota
      • Rochester, Minnesota, Forenede Stater, 55901
        • Mayo Clinic Labs - Rochester Superior
      • Saint Paul, Minnesota, Forenede Stater, 55101
        • Regions Hospital
      • Saint Paul, Minnesota, Forenede Stater, 55101
        • Regions Cancer Care Center
      • Saint Paul, Minnesota, Forenede Stater, 55101
        • Regions Hospital Pharmacy
      • Saint Paul, Minnesota, Forenede Stater, 55130
        • HealthPartners Neurosciences Center
    • Tennessee
      • Nashville, Tennessee, Forenede Stater, 37203
        • Tennessee Oncology PLLC
      • Nashville, Tennessee, Forenede Stater, 37203
        • Tennessee Oncology, PLLC
      • Nashville, Tennessee, Forenede Stater, 37203
        • The Sarah Cannon Research Institute
    • Texas
      • San Antonio, Texas, Forenede Stater, 78229
        • UT Health Cancer Center
    • Utah
      • Salt Lake City, Utah, Forenede Stater, 84106
        • Utah Cancer Specialists
      • Salt Lake City, Utah, Forenede Stater, 84108-1221
        • ARUP Laboratories, Inc.
    • Virginia
      • Charlottesville, Virginia, Forenede Stater, 22903
        • University of Virginia Cancer Center
      • Charlottesville, Virginia, Forenede Stater, 22908
        • UVA Health System

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Key Inclusion Criteria

All Study Parts:

  • Diagnosis of cancer that has been histologically or cytologically confirmed
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1

Part A (1 of the following):

  • Ovarian cancer, triple-negative breast cancer, head and neck squamous cell cancer, bladder cancer, metastatic colorectal cancer, pancreatic ductal adenocarcinoma, or gastric cancer that is measurable or evaluable, nonmeasurable as defined by RECIST v1.1 and meets 1 of the following criteria:

    • is refractory to standard of care
    • no standard therapy available
    • patient refuses standard therapy
  • Advanced, unresectable, or metastatic melanoma with or without prior treatment and measurable or evaluable, nonmeasurable disease as defined by RECIST v1.1

  • Advanced/metastatic PD-L1-positive NSCLC (defined as a tumor proportion score [TPS] ≥ 50%) with measurable or evaluable, non-measurable disease as defined by RECIST v1.1 (1 of the following):

    • 1) No prior systemic chemotherapy if tumor does not have EGFR or ALK genomic aberrations
    • 2) Disease progression on or after platinum-containing chemotherapy;
    • 3) If tumor has EGFR or ALK genomic aberrations, disease progression on an FDA-approved therapy for EGFR or ALK genomic tumor aberrations

Phase 2 (1 of the following):

  • Advanced/metastatic solid tumor with PD as defined by RECIST 1.1 or irRC on an anti-PD-1- or anti-PD-L1-containing regimen as their most recent prior therapy
  • Advanced/metastatic epithelial ovarian cancer, peritoneal cancer or tubal cancer with measurable disease as defined by RECIST 1.1, that had progressed within 6 months of completing ≥ 4 cycles of platinum-based therapy
  • Advanced/metastatic PDA that is locally advanced, unresectable or metastatic with measurable disease as defined by RECIST v1.1 in patients who have received at least one prior line of systemic therapy for their disease

Key Exclusion Criteria

  1. Prior treatment as follows:

    • Part A: an immune CPI (e.g., PD-1, PD-L1, or cytotoxic T-lymphocyte antigen 4 [CTLA-4] inhibitor).

    NOTE: For patients with melanoma, prior treatment with ipilimumab is allowed if it was administered as adjuvant therapy and treatment was completed at least 3 months prior to enrollment.

    • Phase 2:

      • A CSF-1R inhibitor or CSF-1 (or MCSF) inhibitor.
      • prOVCA and PDA patients only: an immune CPI (e.g., PD-1, PD-L1, or CTLA-4 inhibitor)
  2. Symptomatic brain metastasis at screening
  3. Active autoimmune disease, documented history of autoimmune syndrome or disease, or a chronic medical condition that requires chronic steroid therapy or immunosuppressive medication
  4. History of pneumonitis or interstitial lung disease
  5. Severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study
  6. Ocular melanoma

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Phase 1b/Part A
Patients in Part A will receive escalating doses of single-agent ARRY-382 in combination with 2 mg/kg pembrolizumab.
Medicin: ARRY-382
ARRAY-382 will be taken by mouth once daily at a fixed dose.
Medicin: Pembrolizumab
Pembrolizumab will be administered intravenously over 30 minutes every 3 weeks.
Eksperimentel: Phase 2
Patients in Phase 2 will receive the MTD/RP2D dose of ARRY-382 determined during Part A in combination with 200mg pembrolizumab.
Medicin: ARRY-382
ARRAY-382 will be taken by mouth once daily at a fixed dose.
Medicin: Pembrolizumab
Pembrolizumab will be administered intravenously over 30 minutes every 3 weeks.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Phase 1b, Part A: Number of Participants With Dose-Limiting Toxicities (DLT)
Tidsramme: Cycle 1 (up to 21 days)
DLT: adverse event (AE) or abnormal laboratory value not clearly attributable to an extraneous cause, such as disease progression, intercurrent illness, or concomitant medications occurring during 21 days of Cycle 1, met 1 of the criteria A) nonhematologic AEs: recurring grade 2 pneumonitis, grade 3 events (irAE, QTcF prolongation, rash; other grade 3/4 except alopecia, nausea, diarrhea, vomiting, tumor flare, pseudoprogression, endocrinopathy); B) hematology AEs/laboratory abnormalities: grade 4 events except lymphopenia, neutropenia, electrolyte imbalances or abnormalities, grade 3 thrombocytopenia, febrile neutropenia, grade 4 AST/ALT elevation, grade 3 AST/ALT elevation lasting >7 days, associated with bilirubin levels>=2*ULN or international normalized ratio >1.5, grade 3 bilirubin elevation >=3, CK elevation >=grade 3 lasting, increase in creatinine >=1.5*baseline value, dose delay (dose interruption for >14 days) or other (inability to receive at least 67% of ARRY-382 doses).
Cycle 1 (up to 21 days)
Phase 2 Cohorts: Objective Response Rate (ORR)
Tidsramme: From day of first dose to 30 days after last dose (maximum up to 13.5 months)
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator review of radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. As per RECIST v1.1: CR = disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR = at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). The analysis was based on confirmed responses for which CR or PR must be confirmed by repeat disease assessment studies performed no less than 4 weeks after the criteria for response were first met to qualify as CR or PR, respectively.
From day of first dose to 30 days after last dose (maximum up to 13.5 months)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Phase 1b, Part A: Objective Response Rate (ORR)
Tidsramme: From day of first dose to 30 days after last dose (maximum up to 34.7 months)
ORR was defined as the percentage of participants who achieved a BOR of CR or PR as determined by investigator review of radiographic disease assessments per RECIST v1.1. As per RECIST v1.1: CR = disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures <10 mm. PR = at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non-target lesions must be non-PD. The analysis was based on confirmed responses for which CR or PR must be confirmed by repeat disease assessment studies performed no less than 4 weeks after the criteria for response were first met to qualify as CR or PR, respectively.
From day of first dose to 30 days after last dose (maximum up to 34.7 months)
Phase 1b, Part A and Phase 2 Cohorts: Duration of Response (DOR)
Tidsramme: From date of first documented CR or PR up to disease progression or death (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
DOR was defined as the time from the date of the first documented response (CR or PR) to the earliest date of disease progression, or death due to any cause after achieving a response. As per RECIST v1.1: CR = disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures < 10 mm. PR = at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >= 5 mm or appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions. DOR was estimated using the Kaplan-Meier method.
From date of first documented CR or PR up to disease progression or death (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Progression-Free Survival (PFS)
Tidsramme: From day of first dose until disease progression or death due to any cause or till last tumor assessment date (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v1.1, or death due to any cause, whichever occurs first. If a participant did not have a PFS event at the time of the analysis cut-off or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >= 5 mm or appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.
From day of first dose until disease progression or death due to any cause or till last tumor assessment date (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Overall Survival (OS)
Tidsramme: From day of first dose till death due to any cause or date of last contact (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
OS was defined as the time from the start of treatment to the date of death due to any cause. If a death was not observed by the date of the analysis cut-off, OS was censored at the date of last contact. OS was estimated using the Kaplan-Meier method.
From day of first dose till death due to any cause or date of last contact (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Percentage of Participants With Immune-Related Response Rate (irRR)
Tidsramme: From day of first dose till up to end of study treatment (for Phase 1b: maximum up to 33.7 months, for Phase 2: maximum up to 12.5 months)
irRR was defined as the percentage of participants who achieved immune-related best overall response (irBOR) of immune-related CR (irCR) or immune-related PR (irPR), as determined by the investigator per immune related response criteria (irRC). irBOR was the best response using irRC recorded from the start of study treatment until the end of treatment. irCR was the disappearance of all target lesions, irPR was a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation.
From day of first dose till up to end of study treatment (for Phase 1b: maximum up to 33.7 months, for Phase 2: maximum up to 12.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Immune-Related Progression-Free Survival (irPFS)
Tidsramme: From the start of treatment to the time of first documented progression, or death (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
irPFS was defined as the time from the start of treatment to the time of first documented progression per irRC, or death due to any cause. irRC criteria for progression for 1) Measurable new lesions: incorporated into the tumor burden (eg, added to the index lesions); do not define progression unless the total measurable tumor burden increases by the required amount (25%); 2) New non-measurable lesions: not considered progression if the total measurable tumor burden is stable or shrinking. For the analysis of irPFS, Kaplan-Meier method was used.
From the start of treatment to the time of first documented progression, or death (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 2 prOVCA: Change From Baseline in Tumor Markers at Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, Day 8, 15 of Cycle 1 and Treatment Discontinuation
Tidsramme: Baseline, Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, Day 8, 15 of Cycle 1 and Treatment discontinuation (before 13.5 months)
Tumor markers were measured for tumor type from serum samples obtained from participants in Phase 2. Mean change from baseline was reported in this outcome measure.
Baseline, Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, Day 8, 15 of Cycle 1 and Treatment discontinuation (before 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Tidsramme: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Newly Occurring or Worsening Serum Chemistry Laboratory Abnormalities Graded by Common Terminology Criteria for Adverse Events (CTCAE) Grade 4.03
Tidsramme: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Abnormalities: Albumin (hypoalbuminemia),Alkaline phosphatase (ALP increased), Alanine aminotransferase (ALT increased), Aspartate aminotransferase (AST increased),Total bilirubin (TBL increased), Creatinine (increased), Corrected calcium (hypocalcemia/hypercalcemia), Creatine kinase (CK increased), Glucose (hypoglycemia/hyperglycemia), Amylase (increased), Lipase (increased) ,Phosphate (hypophosphatemia), Magnesium (hypomagnesemia/hypermagnesemia), Potassium (hypokalemia/hyperkalemia), Sodium (hyponatremia/hypernatremia). Participants with all grades and grade 3/4 abnormalities were reported. Test abnormalities were graded by CTCAE v4.03 as Grade 1=mild; Grade 2=moderate; Grade 3/Grade 4=severe/life-threatening.
First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Newly Occurring or Worsening Hematology and Coagulation Laboratory Abnormalities Graded by CTCAE Grade 4.03
Tidsramme: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Hematology abnormalities: Hemoglobin (anemia/hemoglobin increased), Platelets (count decreased), Leukocytes (count decreased/increased), Neutrophils (count decreased), Lymphocytes (count increased/decreased). Coagulation abnormalities: International Normalized Ratio (INR increased), Partial thromboplastin time(PTT)/Activated partial thromboplastin Time (aPTT, time prolonged). Abnormalities were graded by CTCAE grade 4.03 as Grade 1= mild; Grade 2 = moderate; Grade 3/Grade 4 = severe/life-threatening. Participants with all grades and grade 3/4 abnormalities were reported.
First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Newly Occurring Abnormal Liver Function Tests
Tidsramme: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Liver function parameters/abnormalities: Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT): >3* upper limit of normal (ULN), >5*ULN, >8*ULN, >10*ULN, >20*ULN; Bilirubin >1.5*ULN, >2*ULN; Alkaline phosphatase (ALP) >2*ULN, >3*ULN.
First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Shift in Thyroid Panel Severity From Baseline Grade to Post Baseline Grades
Tidsramme: Baseline, 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Thyroid panel laboratory parameters/abnormalities: thyrotropin, free triiodothyronine (T3), free thyroxine (T4). Shift in thyroid panel severity from baseline grade low, normal, high and missing to the post baseline grades as low, normal, high and missing is reported in this outcome measure.
Baseline, 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Clinically Significant Urinalysis Finding
Tidsramme: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Urinalysis laboratory parameters/abnormalities: Decimal logarithm of reciprocal of hydrogen ion activity (pH), specific gravity, protein, glucose, ketones, nitrite, blood, leukocyte esterase, microscopy (if urine tested positive for blood or protein). Clinical significance was judged by investigator.
First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Number of Participants With Newly Occurring Clinically Notable Vital Sign Abnormalities
Tidsramme: First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body temperature and weight. Low SBP: less than or equal to (<=)90 millimeter of mercury (mmHg) with decrease from baseline of >=20 mmHg. High SBP: >=160 mmHg with increase from baseline of >=20 mmHg. Low DBP: <=50 mmHg with decrease from baseline of >=15 mmHg. High DBP: >=100 mmHg with increase from baseline of >=15 mmHg. Low heart rate: <=50 beats/min with decrease from baseline of >=15 beats/min. High heart rate: >=120 beats/min with increase from baseline of >=15 beats/min. Low temperature: <=36 degree Celsius (C). High temperature: >=37.5 degree C. Low Weight: decrease from baseline >=20%. High weight: increase from baseline >=10%.
First dose of study drug up to 30 days after last dose (for Phase 1b: maximum up to 34.7 months, for Phase 2: maximum up to 13.5 months)
Phase 1b, Part A and Phase 2 Cohorts: Plasma Concentration Versus Time Profile of ARRY-382
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hour(hr) (±5 min), 2 hours(hrs) (±10 min), 4 hrs (±20 min) and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
The lower limit of quantitation (LLOQ) for analyte ARRY-382 was 5.00 nanogram per milliliter (ng/mL).
Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hour(hr) (±5 min), 2 hours(hrs) (±10 min), 4 hrs (±20 min) and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
Phase 1b, Part A and Phase 2 Cohorts: Plasma Concentration Versus Time Profile of Metabolite AR00469099
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
Drug ARRY-382 had its three metabolites AR00469099, AR00469100 and AR00470870. Plasma concentration of metabolite AR00469099 was reported in this outcome measure. The LLOQ for analyte AR00469099 was 1.00 ng/mL.
Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
Phase 1b, Part A and Phase 2 Cohorts: Plasma Concentration Versus Time Profile of Metabolite AR00469100
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
Drug ARRY-382 had its three metabolites AR00469099, AR00469100 and AR00470870. Plasma concentration of metabolite AR00469100 was reported in this outcome measure. The LLOQ for analyte AR00469100 was 1.00 ng/mL.
Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
Phase 1b, Part A and Phase 2 Cohorts: Plasma Concentration Versus Time Profile of Metabolite AR00470870
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
Drug ARRY-382 had its three metabolites AR00469099, AR00469100 and AR00470870. Plasma concentration of metabolite AR00470870 was reported in this outcome measure. The LLOQ for analyte AR00470870 was 1.00 ng/mL.
Pre dose of ARRY-382 (120 minutes prior to administration): on Day 15 of Cycle 1, on Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9 , 10; 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) post dose of ARRY-382 on Day 1 of Cycle 1, 2
Phase 1b, Part A and Phase 2 Cohorts: Area Under the Plasma Concentration-Time Curve Over a Dosing Interval at Steady-State (AUCtau, ss) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
Tidsramme: 0 to 24 hrs after administration of ARRY-382 on Day 1 of Cycle 2
AUCtau was defined as area under the plasma concentration-time curve over the dosing interval, where dosing interval was 24 hours.
0 to 24 hrs after administration of ARRY-382 on Day 1 of Cycle 2
Phase 1b, Part A and Phase 2 Cohorts: Maximum Observed Plasma Concentration (Cmax) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration), 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
Cmax was obtained from plasma concentration time curve. Cmax at single dose was reported at Cycle1 Day 1 and Cmax at steady state was reported at Cycle 2 Day 1.
Pre dose of ARRY-382 (120 minutes prior to administration), 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
Phase 1b, Part A and Phase 2 Cohorts: Ctrough at Steady State for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration) on Day 1 of Cycle 2
Measured concentration at the pre-dose at steady-state.
Pre dose of ARRY-382 (120 minutes prior to administration) on Day 1 of Cycle 2
Phase 1b, Part A and Phase 2 Cohorts: Time to Reach Maximum Observed Plasma Concentration (Tmax) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration), 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
Tmax was obtained from plasma concentration time curve. Tmax at single dose was reported at Cycle 1 Day 1 and Tmax at steady state was reported at Cycle 2 Day 1.
Pre dose of ARRY-382 (120 minutes prior to administration), 1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
Phase 1b, Part A and Phase 2 Cohorts: Metabolite-to-Parent Ratio (MR) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration),1 hrs (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
Different MR reported for single dose calculated at Cycle 1 Day 1 were as follows: 1) MRAUClast = ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, where AUClast was area under the plasma concentration-time curve from zero to the last measurable time point; 2) MRCmax = ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight. Different MR reported for steady state calculated at Cycle 2 Day 1 were as follows: 1) MRAUCtau,ss = ratio of AUCtau,ss values of the metabolite compared to parent, corrected for molecular weight, where AUCtau was area under the plasma concentration-time curve over a dosing interval at steady-state; 2) MRCmax,ss = Ratio of Cmax,ss values of the metabolite compared to parent, corrected for molecular weight.
Pre dose of ARRY-382 (120 minutes prior to administration),1 hrs (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
Phase 1b, Part A and Phase 2 Cohorts: Accumulation Ratio (R) for ARRY-382 and Metabolites (AR00469099, AR00469100, and AR00470870)
Tidsramme: Pre dose of ARRY-382 (120 minutes prior to administration),1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2
Accumulation ratio was calculated and reported for Cmax as RCmax and for AUC as RAUC. RCmax = Cmax at steady-state on Day 1 of Cycle 2 divided by Cmax on Day 1 of Cycle 1. RAUC = AUC from zero to 8 hours after drug administration at steady-state on Day 1 of Cycle 2 divided by AUC from zero to 8 hours after drug administration on Day 1 of Cycle 1.
Pre dose of ARRY-382 (120 minutes prior to administration),1 hr (±5 min), 2 hrs (±10 min), 4 hrs (±20 min), and 8 hrs (±30 min) after administration of ARRY-382 on Day 1 of Cycle 1 and 2

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Pfizer

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

1. september 2016

Primær færdiggørelse (Faktiske)

17. september 2019

Studieafslutning (Faktiske)

24. oktober 2019

Datoer for studieregistrering

Først indsendt

2. august 2016

Først indsendt, der opfyldte QC-kriterier

23. august 2016

Først opslået (Skøn)

26. august 2016

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

16. juni 2022

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

21. maj 2022

Sidst verificeret

1. maj 2022

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • ARRAY-382-201
  • C4261001 (Anden identifikator: Alias Study Number)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

Ja

IPD-planbeskrivelse

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

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 .

Kliniske forsøg med Avancerede solide tumorer

Kliniske forsøg med ARRY-382

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Bahrain

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner