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En studie av CA-4948 hos pasienter med residiverende eller refraktære hematologiske maligniteter

1. oktober 2026 oppdatert av: Curis, Inc.

TakeAim-lymfom: En åpen studie, doseeskalering og doseutvidelse som evaluerer sikkerheten, farmakokinetikken, farmakodynamikken og den kliniske aktiviteten til oralt administrert CA-4948 hos pasienter med residiverende eller refraktære hematologiske maligniteter

This is a multi-center, open-label study to evaluate the safety, pharmacokinetics (PK), and anti-cancer activity of oral administration of emavusertib alone or in combination with ibrutinib in adult participants with relapsed or refractory (R/R) hematologic malignancies.

This trial will be completed in four parts. In Part A1, emavusertib will be evaluated first in a dose escalating monotherapy setting to establish the safety and tolerability (complete). In Part A2, emavusertib will be evaluated in combination with ibrutinib at 560 milligrams (mg) once daily (QD) or 420 mg QD as indicated by disease (Part A2 complete).

Part B will comprise 2 cohorts to assess safety and efficacy of emavusertib in combination with ibrutinib in participants with R/R primary central nervous system lymphoma (PCNSL) who have directly progressed on a bruton tyrosine kinase inhibitor (BTKi). In this part of the study, emavusertib will be dosed at 100 mg or 200 mg twice daily (BID) in combination with ibrutinib in 28-day treatment cycles.

Part C will comprise 3 treatment arms in the second-line setting to assess the efficacy and safety of emavusertib monotherapy, ibrutinib monotherapy, and emavusertib in combination with ibrutinib in participants with R/R PCNSL who are naïve to BTKi treatment. In this part of the study, eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will be randomized 1:1:1 to 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Antatt)

152

Fase

  • Fase 2
  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

  • Forente stater
    • Arizona
      • Phoenix, Arizona, Forente stater, 85013
        • Rekruttering
        • St. Joseph's Hospital and Medical Center
      • Phoenix, Arizona, Forente stater, 85054
        • Fullført
        • Mayo Clinic
    • California
      • Duarte, California, Forente stater, 91010
        • Rekruttering
        • City of Hope
      • Santa Monica, California, Forente stater, 90404
        • Rekruttering
        • Providence St. John's Health Center
      • Santa Monica, California, Forente stater, 90404
        • Tilbaketrukket
        • UCLA Department of Medicine - Hematology/Oncology
    • Connecticut
      • New Haven, Connecticut, Forente stater, 06510
        • Fullført
        • Smilow Cancer Hospital at Yale-New Haven
    • Florida
      • Jacksonville, Florida, Forente stater, 32224
        • Rekruttering
        • Mayo Clinic
    • Illinois
      • Chicago, Illinois, Forente stater, 60611
        • Rekruttering
        • Northwestern Memorial Hospital
    • Massachusetts
      • Boston, Massachusetts, Forente stater, 02215
        • Rekruttering
        • Dana Farber Cancer Institute
    • Minnesota
      • Rochester, Minnesota, Forente stater, 55905
        • Rekruttering
        • Mayo Clinic
    • Nebraska
      • Omaha, Nebraska, Forente stater, 68198
        • Rekruttering
        • Fred and Pamela Buffett Cancer Center
    • New Jersey
      • Hackensack, New Jersey, Forente stater, 07601
        • Fullført
        • Hackensack University Medical Center
    • New York
      • Buffalo, New York, Forente stater, 14263
        • Rekruttering
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, Forente stater, 10065
        • Rekruttering
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, Forente stater, 10032
        • Tilbaketrukket
        • Columbia University Irving Medical Center
      • New York, New York, Forente stater, 10029
        • Rekruttering
        • Mt Sinai
    • North Carolina
      • Durham, North Carolina, Forente stater, 27710
        • Rekruttering
        • Duke University Medical Center, Duke Cancer Center
    • Ohio
      • Cleveland, Ohio, Forente stater, 44195
        • Rekruttering
        • Cleveland Clinic
    • Oregon
      • Portland, Oregon, Forente stater, 97225
        • Rekruttering
        • Providence Neurological Specialties West
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater, 19104
        • Fullført
        • Hospital of the University of Pennsylvania
      • Pittsburgh, Pennsylvania, Forente stater, 15232
        • Rekruttering
        • UPMC Hilman Cancer Center
    • Tennessee
      • Knoxville, Tennessee, Forente stater, 37920
        • Fullført
        • University of Tennessee Medical Center
    • Texas
      • Dallas, Texas, Forente stater, 75235
        • Aktiv, ikke rekrutterende
        • UT Southwestern Medical Center
      • Houston, Texas, Forente stater, 77030
        • Rekruttering
        • The University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, Forente stater, 84112
        • Rekruttering
        • Huntsman Cancer Institute, University of Utah
    • Washington
      • Seattle, Washington, Forente stater, 98195
        • Rekruttering
        • University of Washington Medical Center
      • Seattle, Washington, Forente stater, 98104
        • Fullført
        • Swedish Cancer Institute
  • Frankrike
      • Bordeaux, Frankrike
        • Rekruttering
        • Institut Bergonie
      • Marseille, Frankrike
        • Rekruttering
        • Hopital de la Timone
      • Paris, Frankrike
        • Rekruttering
        • Hospital Pitie Salpetriere
      • Paris, Frankrike
        • Rekruttering
        • Institut Curie Hospital
  • Israel
      • Beersheba, Israel
        • Rekruttering
        • Hematology Department Soroka UMC / Heanatology Department
      • Haifa, Israel
        • Rekruttering
        • Rambam Medical Center
      • Jerusalem, Israel
        • Rekruttering
        • Hadassah Medical Center / Ein-Carem
  • Italia
      • Cuneo, Italia
        • Rekruttering
        • Università di Torino Croce e Carle
      • Florence, Italia
        • Rekruttering
        • SODc Ematologia Azienda Ospedaliera Universitaria Careggi
      • Meldola, Italia
        • Rekruttering
        • IRST - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Milan, Italia
        • Rekruttering
        • IRCCS San Raffaele Scientific Institute
  • Polen
      • Gdansk, Polen
        • Rekruttering
        • Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
      • Krakow, Polen
        • Tilbaketrukket
        • Oddzial Kliniczny Hematologii
      • Warsaw, Polen
        • Rekruttering
        • NarodowyInstytutu Onkologii im. Marii Sklodowskiej-Curie-Panstwowy Instytutu Badawczy
  • Spania
      • Barcelona, Spania
        • Rekruttering
        • University Hospital Vall d'Hebron
      • Madrid, Spania
        • Rekruttering
        • MD Anderson Cancer Center Madrid
      • Seville, Spania
        • Rekruttering
        • Hospital Universitario Virgen del Rocio
  • Tsjekkia
      • Prague, Tsjekkia
        • Rekruttering
        • Všeobecná fakultní nemocnice v Praze

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:

  1. Males and females greater than or equal to 18 years of age

  2. Life expectancy of at least 3 months

  3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

  4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable). Cerebral biopsies are not required if imaging reveals typical images of PCNSL.

    1. Participants with parenchymal lesions must have unequivocal evidence of disease progression (e.g., presence of at least 1 measurable target lesion [≥ 10 millimeters (mm) and ≤ 40 mm in the longest diameter on brain magnetic resonance imaging [MRI] or head computed tomography [CT] on imaging within 28 days prior to Cycle 1 Day 1]). In cases where the tumor size is smaller but still measurable and located at a critical central nervous system (CNS) location, disabling the participant and/or causing symptoms, this participant may be eligible following a discussion with the Sponsor Medical Monitor.
    2. For participants limited to leptomeningeal involvement, cerebrospinal fluid (CSF) analysis (cytology and/or flow cytometry) with or without additional imaging (MRI) of the spine as clinically indicated is required to document abnormal cells within 28 days prior to Cycle 1 Day 1.

Exclusion Criteria for Part B and Part C

  1. Participants with only intraocular PCNSL without brain lesion or CSF involvement, T-cell lymphoma, systemic presence of lymphoma, or non-CNS lymphoma metastatic to the CNS

  2. Evidence of systemic lymphoma. This must be demonstrated by a positron emission tomography (PET) scan (or CT scan with contrast if applicable) of the chest, abdomen, and pelvis at Screening (testicular ultrasound may be considered to exclude a testicular lymphoma disseminated to the brain).

  3. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior history of systemic lymphoma, unless the participant has been free of the disease for ≥ 3 years.

  4. Active malignancy other than PCNSL requiring systemic therapy

  5. Previous BTKi treatment (Part C only).

  6. History of Grade ≥ 3 rhabdomyolysis without complete recovery

  7. Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.

  8. Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.

  9. Received prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to Cycle 1 Day 1; or had clinically significant graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior to Screening (with the exception of a BTKi for Part B only).

    Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical Monitor approval

  10. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1 (with the exception of ibrutinib or other BTKi for Part B only, which may be continued until the day before Cycle 1 Day 1)

  11. Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of their excipients.

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: Sekvensiell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Emavusertib (CA-4948) dose escalation

Part A1: Dose-level cohorts with up to approximately 6 participants each will be used to define the Maximum Tolerated Dose (MTD) for emavusertib.
Legemiddel: Emavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

Andre navn:
  • CA-4948
Eksperimentell: Emavusertib (CA-4948) and ibrutinib dose escalation

Part A2: Evaluate escalating dose levels of oral emavusertib in combination with 560 mg QD or 420 mg QD of oral ibrutinib. The starting dose of emavusertib to be used in combination will be 200 mg BID. It is anticipated that 12 to 20 participants at a potential dose level will be required to establish optimal combination dosing.
Legemiddel: Emavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

Andre navn:
  • CA-4948
Legemiddel: Ibrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Eksperimentell: Emavusertib (CA-4948) and ibrutinib dose expansion

In two Expansion Cohorts (Part B), emavusertib in combination with ibrutinib will be administered in participants with R/R PCNSL who have progressed on a BTKi. In Cohort 1, emavusertib 100 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles. In Cohort 2, emavusertib 200 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles.
Legemiddel: Emavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

Andre navn:
  • CA-4948
Legemiddel: Ibrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Eksperimentell: Emavusertib (CA-4948) and ibrutinib

In this part of the study (Part C), eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will receive 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD. Treatments will be administered continuously in 28-day treatment cycles.
Legemiddel: Emavusertib

Emavusertib will be provided as a tablet dosage form to be taken BID.

Andre navn:
  • CA-4948
Legemiddel: Ibrutinib

Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Del B: Overall Response Rate (ORR) hos deltakere med R/R PCNSL
Tidsramme: 18 måneder
18 måneder
Del C: ORR hos deltakere med R/R PCNSL
Tidsramme: 18 måneder
18 måneder
Part A: To determine the safety and tolerability of emavusertib as a monotherapy and in combination with ibrutinib: dose-limiting toxicity (DLT)
Tidsramme: 12 months

The number of participants with a dose-limiting toxicity (DLT) in the first treatment cycle
12 months
Part A: Maximum tolerated dose (MTD) of emavusertib as a monotherapy and in combination with ibrutinib measured by dose-limiting toxicities (DLTs)
Tidsramme: 12 months

MTD determined by the highest dose level studied at which fewer than 2 out of 6 subjects (<33%) experience a dose limiting toxicity.
12 months
Part A: Recommended Phase 2 Dose (RP2D) of emavusertib as a monotherapy and in combination with ibrutinib based on overall tolerability data
Tidsramme: 12 months

RP2D selected based on overall tolerability data from all participants treated at different dose levels and will not exceed the MTD.
12 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by AUC
Tidsramme: 24- 66 months

Area Under the concentration-time curve (AUC)
24- 66 months
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Cmax
Tidsramme: 24- 66 months

Maximum plasma concentration (Cmax)
24- 66 months
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Cmin
Tidsramme: 24- 66 months

Minimum plasma concentration (Cmin)
24- 66 months
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by Tmax
Tidsramme: 24- 66 months

Time to maximum plasma concentration (Tmax)
24- 66 months
Parts A, B and C: Pharmacokinetic (PK) profile of emavusertib and ibrutinib measured by plasma terminal half-life
Tidsramme: 24- 66 months

Plasma terminal elimination half-life (T 1/2)
24- 66 months
Part A: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib measured by ORR
Tidsramme: 24- 36 months

Assessed by ORR
24- 36 months
Parts A, B and C: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib and ibrutinib as monotherapy measured by duration of response (DOR)
Tidsramme: 24- 66 months

Assessed by DOR
24- 66 months
Part A: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib measured by disease control rate (DCR)
Tidsramme: 24- 36 months

Assessed by DCR
24- 36 months
Parts A, B and C: To assess efficacy of emavusertib as a monotherapy and in combination with ibrutinib and ibrutinib as monotherapy measured by progression free survival (PFS)
Tidsramme: 24- 66 months

Assessed by PFS
24- 66 months
Parts A, B and C: To assess efficacy of emavusertib as a monotherapy, in combination with ibrutinib and ibrutinib as monotherapy measured by overall survival (OS)
Tidsramme: 24 - 66 months

Assessed by OS
24 - 66 months
Parts B and C: To assess the safety and tolerability of emavusertib as monotherapy, ibrutinib as monotherapy and emavusertib in combination with ibrutinib in participants with R/R PCNSL
Tidsramme: up to 66 months

Measured by the number of participants with treatment-emergent adverse events (TEAEs) and treatment-related adverse events
up to 66 months

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Curis, Inc.

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)

28. desember 2017

Primær fullføring (Antatt)

1. juli 2027

Studiet fullført (Antatt)

1. oktober 2027

Datoer for studieregistrering

Først innsendt

17. oktober 2017

Først innsendt som oppfylte QC-kriteriene

27. oktober 2017

Først lagt ut (Faktiske)

1. november 2017

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

6. oktober 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

1. oktober 2026

Sist bekreftet

1. oktober 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • CA-4948-101
  • 2024-513312-95-00 (Ctis)
  • 2022-000891-20 (EudraCT-nummer)

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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