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Study of Preladenant (MK-3814) Alone and With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3814A-062)

25. februar 2019 oppdatert av: Merck Sharp & Dohme LLC

A Phase Ib/II Study to Evaluate the Safety and Tolerability of Preladenant as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Malignancies

The purpose of this study is to evaluate the safety and preliminary efficacy of preladenant (MK-3814A) alone and in combination with pembrolizumab (MK-3475) (pembro) in participants with advanced solid tumors that have not responded to prior therapy. This study will be done in 2 parts. Part 1 will identify and confirm the recommended Phase 2 dose (RP2D) of preladenant when given alone or in combination with pembrolizumab. Part 2 of the study will determine the safety and efficacy of preladenant in combination with pembrolizumab at the RP2D in participants with select solid tumors .

Studieoversikt

Status

Avsluttet

Forhold

Studietype

Intervensjonell

Registrering (Faktiske)

10

Fase

  • Fase 1

Kontakter og plasseringer

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

Studiesteder

    • Ontario
      • Toronto, Ontario, Canada, H9H 4M7
        • Princess Margaret Hospital ( Site 0010)
    • Quebec
      • Montreal, Quebec, Canada, H9H 4M7
        • Jewish General Hospital ( Site 0011)
    • Michigan
      • Grand Rapids, Michigan, Forente stater, 49546
        • START Midwest ( Site 0001)
      • Haifa, Israel
        • Rambam Health Care Campus ( Site 0020)
      • Tel Aviv, Israel
        • Tel Aviv Sourasky Medical Center ( Site 0021)

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:

  • Has a histologically- or pathologically-documented, locally-advanced or metastatic solid tumor for which standard therapy, either does not exist or has been proven ineffective, intolerable or refused by the participant. Each participant must have received at least one and up to five prior lines of cancer treatment regimens, excluding neo-adjuvant, adjuvant, maintenance treatment and surgery
  • Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion)
  • Has measurable disease per RECIST 1.1
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Females must not be pregnant
  • Female and male participants of reproductive potential must agree to use adequate contraception starting from the first dose of study therapy, throughout the study period, and for up to 120 days after the last dose of study therapy

Exclusion Criteria:

  • Has disease that is suitable for local treatment administered with curative intent
  • Has received previous treatment with an immunomodulatory agent (e.g, anti- Programmed Cell Death Receptor 1/ Programmed Cell Death Receptor Ligand 1 or anti-cytotoxic T-lymphocyte-associated antigen-4) and was discontinued from treatment due to a Grade 3 or higher immune-related adverse event
  • Has received previous treatment with an adenosine A2a receptor antagonist (e.g. CPI-444, HTL1071, PBF-509)
  • Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks of the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) grade 1 or better from any adverse event
  • Is currently participating or has participated in a study with an investigational agent or using an investigational device within 28 days of the first dose of study therapy
  • Is currently taking or has taken drugs that interfere with Cytochrome P450 (CYP)3A4 or CYP2C8 or grapefruit and star fruit in diet within 14 days of the first dose of study therapy
  • Is currently taking or has taken proton pump inhibitors within 5 days of the first dose of study therapy
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of the first dose of study therapy
  • Is expected to require any other form of systemic or localized antineoplastic therapy while on study
  • Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years
  • Has clinically active central nervous system metastases and/or carcinomatous meningitis
  • History of a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study drug
  • Has an active infection requiring therapy
  • History of interstitial lung disease
  • History of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • History of active tuberculosis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
  • Has received a live-virus vaccine within 30 days of the first dose of study therapy
  • Has known Human Immunodeficiency Virus (HIV) (HIV 1 or 2 antibodies) and/or known active and acute Hepatitis B or C infections
  • Has known psychiatric or substance abuse disorders that would interfere with the ability to cooperate with the requirements of the study
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
  • Has not fully recovered from any effects of major surgery without significant detectable infection
  • Has had surgery that required general anesthesia within 2 weeks of the first dose of study therapy
  • Has had surgery that required regional/epidural anesthesia within 72 hours of the first dose of study therapy

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: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Preladenant 25 mg Twice a Day (BID)
During an initial dose evaluation phase, participants received 25 mg of preladenant orally twice a day (BID) on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was to be established based on the number of dose limiting toxicities (DLTs) at each dose level administered. Participants continued receiving 25 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle
Andre navn:
  • MK-3814A
Eksperimentell: Preladenant 50 mg BID
During an initial dose evaluation phase, participants received 50 mg of preladenant orally BID on Days 1 through 21 of each 21-day cycle (for a maximum of 35 cycles) until the RP2D could be established. The RP2D was established based on the number of DLTs at each dose level administered. Participants continued receiving 50 mg of preladenant BID on Days 1 through 21 of each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle
Andre navn:
  • MK-3814A
Eksperimentell: Preladenant + Pembrolizumab
During an initial dose evaluation phase, participants received 25 mg of preladenant administered orally BID on Days 1 through 21 in combination with 200 mg pembrolizumab administered as an intravenous (IV) infusion on Day 1 of each 21-day cycle (for a maximum of 35 cycles). Participants continued receiving preladenant 25 mg BID in combination with 200 mg pembrolizumab for each infusion cycle until discontinuation or receiving a maximum of 35 cycles.
Administered as an oral capsule BID on Days 1 through 21 of each 21-day cycle
Andre navn:
  • MK-3814A
Administered as IV infusion on Day 1 of each 21-day cycle
Andre navn:
  • MK-3475
  • KEYTRUDA®

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Participants With Dose-limiting Toxicities (DLTs)
Tidsramme: Cycle 1 (up to 21 days)
DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade (Gr) 4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia with bleeding; Gr 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care; Gr 3 or Gr 4 non-hematologic laboratory value requiring treatment, hospitalization, or persisting for >72 hours; alanine aminotransferase (ALT) or aspartate aminotransferase(AST) >3X upper limit of normal (ULN) WITH total bilirubin >2X ULN with no elevation in alkaline phosphatase (<2X ULN); Febrile neutropenia Gr 3 or 4; discontinuation during Cycle 1 or a >2 week delay in initiating Cycle 2 due to treatment-related toxicity; Missing >25% of preladenant doses as a result of adverse events during Cycle 1; or Gr 5 toxicity.
Cycle 1 (up to 21 days)
Number of Participants Who Experienced at Least One Adverse Event (AE)
Tidsramme: Up tp approximately 8 months
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who experienced at least one AE is presented.
Up tp approximately 8 months
Number of Participants Who Discontinued Study Treatment Due to an AE
Tidsramme: Up to approximately 8 months
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol-specified procedure, whether or not considered related to the medicinal product/protocol-specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. The number of participants who discontinued study treatment due to an AE is presented.
Up to approximately 8 months

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Tidsramme: Up to approximately 8 months
ORR was defined as the percentage of the participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 per investigator review. The ORR per RECIST 1.1 for participants is presented.
Up to approximately 8 months

Samarbeidspartnere og etterforskere

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

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)

27. juni 2017

Primær fullføring (Faktiske)

24. november 2017

Studiet fullført (Faktiske)

21. februar 2018

Datoer for studieregistrering

Først innsendt

30. mars 2017

Først innsendt som oppfylte QC-kriteriene

30. mars 2017

Først lagt ut (Faktiske)

4. april 2017

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

5. juni 2019

Siste oppdatering sendt inn som oppfylte QC-kriteriene

25. februar 2019

Sist bekreftet

1. februar 2019

Mer informasjon

Begreper knyttet til denne studien

Andre studie-ID-numre

  • 3814A-062
  • MK-3814A-062 (Annen identifikator: Merck Protocol Number)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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