Study of INCB053914 in Subjects With Advanced Malignancies
9. november 2021 oppdatert av: Incyte Corporation
A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies
This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies.
The study will be conducted in 4 parts.
Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study).
Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s).
Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).
Studieoversikt
Status
Avsluttet
Forhold
Intervensjon / Behandling
Studietype
Intervensjonell
Registrering (Faktiske)
97
Fase
- Fase 2
- Fase 1
Utvidet tilgang
Godkjent for salg til publikum.
Se utvidet tilgangspost.
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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Arizona
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Tucson, Arizona, Forente stater, 85719
- The University of Arizona Cancer Center
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California
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Sacramento, California, Forente stater, 95817
- UC Davis Comprehensive Cancer Center
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Santa Monica, California, Forente stater, 90095
- UCLA Medical Hematology & Oncology
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Connecticut
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New Haven, Connecticut, Forente stater, 06511
- Yale University
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Florida
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Jacksonville, Florida, Forente stater, 32224
- Mayo Clinic Florida
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Sarasota, Florida, Forente stater, 33916
- Florida Cancer Specialists & Research Institute
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Tampa, Florida, Forente stater, 33612
- H. Lee Moffitt Cancer Center & Research Institute
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Georgia
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Atlanta, Georgia, Forente stater, 30322
- Emory University-Winship Cancer Institute
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Maryland
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Baltimore, Maryland, Forente stater, 21201
- University of Maryland
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Massachusetts
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Boston, Massachusetts, Forente stater, 02215
- Dana-Farber Cancer Center
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Michigan
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Ann Arbor, Michigan, Forente stater, 48109
- University Of Michigan Comprehensive Cancer Center
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Nebraska
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Omaha, Nebraska, Forente stater, 69198
- University of Nebraska Medical Center
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Ohio
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Cincinnati, Ohio, Forente stater, 45236
- Oncology Hematology Care Clinical Trials LLC
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Oklahoma
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Oklahoma City, Oklahoma, Forente stater, 73104
- Stephenson Cancer Center
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Tennessee
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Nashville, Tennessee, Forente stater, 37232
- Vanderbilt University Medical Center
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Nashville, Tennessee, Forente stater, 37203
- Tennessee Oncology
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Texas
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Austin, Texas, Forente stater, 78705
- Texas Oncology
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Tyler, Texas, Forente stater, 75702
- Texas Oncology
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Wisconsin
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Milwaukee, Wisconsin, Forente stater, 53226
- Medical College of Wisconsin
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
18 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
Inclusion Criteria:
- Aged 18 years or older
- Confirmed diagnosis of select advanced malignancy
Parts 1 and 2:
- Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
- Not currently a candidate for curative treatment
Parts 3 and 4:
- Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
- Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive and unfit for intensive chemotherapy.
- Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to 25 mg BID).
- Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
Eastern Cooperative Oncology Group (ECOG) performance status
- Part 1: 0 or 1
- Parts 2, 3 and 4: 0, 1, or 2
- Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.
Exclusion Criteria:
- Inadequate bone marrow or organ function
- Received an investigational agent within 5 half-lives or 14 days, whichever is longer, prior to receiving the first dose of study drug
- Received non-biologic anticancer medication within 5 half-lives prior to receiving the first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28 days for any antibodies or biological therapies
- Prior receipt of a PIM inhibitor
- Any history of disease involving the central nervous system (Part 1). Known active disease involving the central nervous system (Part 2).
- Screening corrected QT interval (QTc) interval > 470 milliseconds
- Radiotherapy within the 2 weeks prior to initiation of treatment
- Chronic or current active infection requiring systemic antibiotic, antifungal, or antiviral treatment
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: Parts 1 and 2: INCB053914 100 mg QD
INCB053914 will be self-administered orally once a day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentell: Parts 3 and 4: INCB053914 + Azacitidine
Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Azacitidine dose will be 75 mg/m^2.
Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
Andre navn:
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Eksperimentell: Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)
I-DAC (intermediate dose cytarabine) will be administered at a dose of 1 g/m2 per day as an infusion as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Cytarabine dose will be 1 g/m^2.
Cytarabine will be administered as an intravenous (IV) infusion.
|
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Eksperimentell: Parts 3 and 4: INCB053914 + Ruxolitinib
Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
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Eksperimentell: Parts 1 and 2: INCB053914 50 mg
INCB053914 will be self-administered orally twice day in as a 50mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentell: Parts 1 and 2: INB053914 65 mg
INCB053914 will be self-administered orally twice day in as a 65mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentell: Parts 1 and 2: INB053914 80 mg
INCB053914 will be self-administered orally twice day in as a 80mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentell: Parts 1 and 2: INB053914 100 mg BID
INCB053914 will be self-administered orally twice day in as a 100mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
|
Eksperimentell: Parts 1 and 2: INB053914 115 mg
INCB053914 will be self-administered orally twice day in as a 115mg immediate release tablet as a monotherapy.
|
Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth. |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Tidsramme: Approximately 7 months
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Approximately 7 months
|
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Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)
Tidsramme: Approximately 2 months
|
The primary efficacy endpoint of ORR in patients with AML who received INCB053914 in combination with cytarabine in Part 4 was not assessed because Part 4 was not opened for enrollment owing to this combination regimen not being tolerated in Part 3.
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Approximately 2 months
|
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Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR
Tidsramme: Approximately 6 months
|
The primary efficacy endpoint of ORR in patients with AML who received INCB053914 plus azacitidine in Part 4 was not performed due to limited enrollment as a result of early study termination.
|
Approximately 6 months
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
|
Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Tidsramme: 1 month
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Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay
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1 month
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Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Tidsramme: Cycle 1 Day 5
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Cycle 1 Day 5
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Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
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Regimen 2 Week 4
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Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
|
Regimen 2 Week 4
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Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Tidsramme: Regimen 2 Week 4
|
Regimen 2 Week 4
|
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Pharmacokinetics: Tmax of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: CL/F of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Cmax of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
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Cycle 1 Day 8
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Pharmacokinetics: Ctau of INCB053914 Monotherapy
Tidsramme: Cycle 1 Day 8
|
Cycle 1 Day 8
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Samarbeidspartnere og etterforskere
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Sponsor
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
29. desember 2015
Primær fullføring (Faktiske)
11. august 2020
Studiet fullført (Faktiske)
11. august 2020
Datoer for studieregistrering
Først innsendt
26. oktober 2015
Først innsendt som oppfylte QC-kriteriene
26. oktober 2015
Først lagt ut (Anslag)
27. oktober 2015
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
8. desember 2021
Siste oppdatering sendt inn som oppfylte QC-kriteriene
9. november 2021
Sist bekreftet
1. november 2021
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- INCB 53914-101
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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