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An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies

6. april 2020 opdateret af: Incyte Corporation

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB052793 in Subjects With Advanced Malignancies

This was a study of INCB052793 given to patients with advanced malignancies that was to be conducted in three phases; Phase 1a (Monotherapy) and Phase 1b (Combination Therapy) and Phase 2 (Combination therapy of INCB052793 with azacitidine and itacitinib with azacitidine). Phase 1 had two parts; a dose escalation (Part 1) and an expansion (Part 2).

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

83

Fase

  • Fase 2
  • Fase 1

Udvidet adgang

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Kontakter og lokationer

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

Studiesteder

  • Forenede Stater
    • Alabama
      • Birmingham, Alabama, Forenede Stater
    • California
      • West Hollywood, California, Forenede Stater
    • Connecticut
      • New Haven, Connecticut, Forenede Stater
    • Georgia
      • Atlanta, Georgia, Forenede Stater
    • Illinois
      • Chicago, Illinois, Forenede Stater
    • Indiana
      • Indianapolis, Indiana, Forenede Stater
    • New Jersey
      • Hackensack, New Jersey, Forenede Stater
    • New York
      • New York, New York, Forenede Stater
    • North Carolina
      • Durham, North Carolina, Forenede Stater
    • Oregon
      • Portland, Oregon, Forenede Stater
    • South Carolina
      • Greenville, South Carolina, Forenede Stater
    • Tennessee
      • Nashville, Tennessee, Forenede Stater
      • Nashville, Tennessee, Forenede Stater
        • Site 2
    • Texas
      • Dallas, Texas, Forenede Stater

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

Inclusion Criteria:

Phase 1a

  • Aged 18 years or older
  • Histologically or cytologically confirmed solid tumor or hematologic malignancy
  • Life expectancy of 12 weeks or longer
  • Must have received ≥ 1 prior treatment regimen
  • Must not be a candidate for potentially curative or standard of care approved therapy

Phase 1b

  • Aged 18 years or older
  • Cohort A: Histologically or cytologically confirmed pancreatic adenocarcinoma, triple-negative breast cancer, urothelial cancer with at least 1 measurable or evaluable target lesion
  • Cohorts B, C, D, E and G: Histologically confirmed multiple myeloma and measureable/evaluable disease
  • Cohort F: Confirmed acute myeloid leukemia or myelodysplastic syndrome
  • Cohort H: Individuals diagnosed with lymphoma

  • Prior therapy:

    • Cohort A: No more than 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy)
    • Cohorts B, C, D, E and G: Must have relapsed from or have been refractory to ≥ 2 prior treatment regimens
    • Cohort F: May have received any number of prior treatment regimens or be treatment-naïve
    • Cohort H: Must have relapsed from or have been refractory to available treatments

Phase 2

  • Aged 18 years or older
  • Cohorts I and J: Confirmed acute myeloid leukemia or high risk myelodysplastic syndrome

  • Prior therapy:

    • Cohorts I and J: Must have failed prior therapy with a hypomethylating agent (HMA)

Exclusion Criteria:

  • Prior receipt of a JAK1 inhibitor (Phase 1a only)
  • Known active central nervous system metastases and/or carcinomatous meningitis
  • Eastern Cooperative Oncology Group (ECOG) performance status > 2
  • Any known contraindications to the use of gemcitabine, nab-paclitaxel, dexamethasone, carfilzomib, bortezomib, lenalidomide, azacitidine, pomalidomide or PI3Kδ inhibitor (Phase 1b and Phase 2 only, as appropriate to treatment cohort)
  • Known human immunodeficiency virus infection, or evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation

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: Parallel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Phase 1a: INCB052793 Monotherapy
Medicin: INCB052793
Initial cohort dose of INCB052793 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria.
Medicin: INCB052793
INCB052793 tablets administered orally at the protocol specified dose strength and frequency.
Eksperimentel: Phase 1b: INCB052793 Combination Therapy
Medicin: INCB052793
Initial cohort dose of INCB052793 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria.
Medicin: INCB052793
INCB052793 tablets administered orally at the protocol specified dose strength and frequency.
Medicin: gemcitabine
Gemcitabine administered intravenously over 30 minutes at the protocol-specified dose and frequency.
Andre navne:
  • Gemzar®
Medicin: nab-paclitaxel
nab-paclitaxel administered intravenously over 30 minutes at the protocol-specified dose and frequency.
Andre navne:
  • Abraxane®
Medicin: dexamethasone
Dexamethasone administered orally at the protocol-specified dose and frequency.
Medicin: Carfilzomib
Carfilzomib administered intravenously at the protocol-specified dose and frequency.
Andre navne:
  • Kyprolis®
Medicin: bortezomib
Bortezomib administered intravenously or subcutaneously at the protocol-specified dose and frequency.
Andre navne:
  • Velcade®
Medicin: lenalidomide
Lenalidomide administered orally at the protocol-specified dose and frequency.
Andre navne:
  • Revlimid®
Medicin: azacitidine
Azacitidine administered subcutaneously at the protocol-specified dose and frequency.
Andre navne:
  • Vidaza®
Medicin: pomalidomide
Pomalidomide administered orally at the protocol-specified dose and frequency.
Andre navne:
  • Pomalyst®
Medicin: INCB050465
INCB050465 tablets administered orally at the protocol specified dose strength and frequency.
Eksperimentel: Phase 2: INCB052793 and itacitinib Combination Therapy
Medicin: INCB052793
Initial cohort dose of INCB052793 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria.
Medicin: INCB052793
INCB052793 tablets administered orally at the protocol specified dose strength and frequency.
Medicin: azacitidine
Azacitidine administered subcutaneously at the protocol-specified dose and frequency.
Andre navne:
  • Vidaza®
Medicin: INCB039110
INCB039110 tablets administered orally at the protocol specified dose strength and frequency.
Andre navne:
  • itacitinib

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Tidsramme: From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 3.4 years)
An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug.
From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 3.4 years)
Phase 2: Objective Response Rate (ORR) in Hematological Malignancies
Tidsramme: Baseline through end of study (Up to approximately 4.5 years)
ORR is defined as the proportion of participants who achieved complete response (CR), CR with incomplete hematologic recovery (CRi), partial response (PR), or hematologic improvement (HI), using the IWG response criteria.
Baseline through end of study (Up to approximately 4.5 years)

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Phase 1A and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment
Tidsramme: Baseline through end of study (Up to approximately 4.5 years)
Response rate is defined as the percentage of participants who achieved best overall response (BOR) as determined by IWG response criteria of investigator's assessment. A participant was considered an objective responder based on the following- Solid tumors: participant had a best overall response (BOR) of CR or PR, Lymphoma: participant had a BOR of complete radiologic response/complete metabolic response or partial remission/partial metabolic response, AML: participant had a BOR of CR, CRi, morphological leukemia-free state (MLFS), or PR, MDS: participant had a BOR of CR, PR, or marrow CR, MDS/myeloproliferative neoplasm (MPN): participant had a BOR of CR, PR, or marrow response, MM: participant had a BOR of stringent CR, CR, very good PR, PR, or MR. Subjects are combined by tumor type for this analysis.
Baseline through end of study (Up to approximately 4.5 years)
Phase 2: Number of Participants With at Least One TEAE and SAE
Tidsramme: From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 1.3 years)
An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug.
From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 1.3 years)
Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Tidsramme: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.
Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Tidsramme: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Tmax is the time to maximum (peak) observed plasma drug concentration. Summary of Steady-State, Day 15, was evaluated by dosing regimen. For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.
Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
Tidsramme: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.
Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration of Itacitinib
Tidsramme: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).
Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for Itacitinib
Tidsramme: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Tmax is the time to maximum (peak) observed plasma drug concentration.
Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for Itacitinib
Tidsramme: Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).
Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Tidsramme: Cycle 1, Day 1
Cmax is defined as the maximum observed plasma concentration measured at Day 1.
Cycle 1, Day 1
Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Tidsramme: Cycle 1, Day 1
Tmax is the time to maximum (peak) observed plasma drug concentration.
Cycle 1, Day 1
Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time t
Tidsramme: Cycle 1, Day 1
AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Cycle 1, Day 1
Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Tidsramme: Cycle 1, Day 15
Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).
Cycle 1, Day 15
Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval
Tidsramme: Cycle 1, Day 15
Minimum observed plasma concentration measured at steady state (Day 15).
Cycle 1, Day 15
Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Tidsramme: Cycle 1, Day 15
Tmax is the time to maximum (peak) observed plasma drug concentration.
Cycle 1, Day 15
Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time
Tidsramme: Cycle 1, Day 15
AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).
Cycle 1, Day 15
Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
Tidsramme: Cycle 1, Day 15
AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Cycle 1, Day 15
Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Tidsramme: Cycle 2, Day 1
Cmax is defined as the maximum observed plasma concentration measured at cycle 2 Day 1.
Cycle 2, Day 1
Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval
Tidsramme: Cycle 2, Day 1
Cmin is defined as the minimal observed plasma concentration measured at cycle 2 Day 1
Cycle 2, Day 1
Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Tidsramme: Cycle 2, Day 1
Tmax is the time to maximum (peak) observed plasma drug concentration.
Cycle 2, Day 1
Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time
Tidsramme: Cycle 2, Day 1
AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Cycle 2, Day 1
Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
Tidsramme: Cycle 2, Day 1
AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Cycle 2, Day 1

Samarbejdspartnere og efterforskere

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

Sponsor

Incyte Corporation

Efterforskere

  • Studieleder: Ekaterine Asatiani, M.D., Incyte Corporation

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)

10. september 2014

Primær færdiggørelse (Faktiske)

27. februar 2019

Studieafslutning (Faktiske)

27. februar 2019

Datoer for studieregistrering

Først indsendt

29. september 2014

Først indsendt, der opfyldte QC-kriterier

10. oktober 2014

Først opslået (Skøn)

16. oktober 2014

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

17. april 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

6. april 2020

Sidst verificeret

1. april 2020

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • INCB 52793-101

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 .

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