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JOURNAL ONKOLOGIE – STUDIE

A Study of MK-6598 as Monotherapy and in Combination With Pembrolizumab (MK-3475) in Advanced Solid Tumors (MK-6598-001)

Rekrutierend

NCT-Nummer:
NCT05594043

Studienbeginn:
Dezember 2022

Letztes Update:
05.09.2023

Wirkstoff:
MK-6598, Pembrolizumab

Indikation (Clinical Trials):
Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 6)

Centre Hospitalier de l'Université de Montréal-Unit for Innovative Therapies ( Site 0100)
H2X 0A9 Montréal
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 5148908444» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

The purpose of this study is to assess the efficacy and safety and establish a preliminary

recommended Phase 2 dose (RP2D) of MK-6598 administered as monotherapy and in combination

with pembrolizumab (MK-3475) in adult participants with advanced or metastatic solid tumors.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by

pathology report and has received, or been intolerant to, all treatment known to

confer clinical benefit.

- Has measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as

assessed by the local site investigator/radiology.

- Has one or more discrete malignant lesions that are amenable to a minimum of 2

separate biopsies.

- Has a baseline tumor sample that can be submitted for analysis.

- Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV

on antiretroviral therapy (ART).

- A participant assigned male sex at birth who receives MK-6598 must agree to use

contraception and should refrain from donating sperm during the specified period(s) of

at least 102 days after study interventions.

- A participant assigned female sex at birth is eligible to participate if not pregnant

or breastfeeding and at least 1 of the following: not a participant of childbearing

potential (POCBP) or a POCBP who agrees to follow the contraceptive guidance during

the treatment period and for up to 120 days after study intervention.

Exclusion Criteria:

- Received prior systemic anticancer therapy including investigational agents within 4

weeks before the first dose of study intervention or has not recovered to CTCAE

Version 5.0 Grade 1 or better from any AEs that were due to cancer therapeutics

administered more than 4 weeks earlier (this includes participants with previous

immunomodulatory therapy with residual immune-related AEs).

- Known additional malignancy that is progressing or has required active treatment

within 2 years.

- Clinically active central nervous system (CNS) metastases and/or carcinomatous

meningitis.

- A severe hypersensitivity (≥Grade 3) reaction to treatment with a monoclonal

antibody/components of the study intervention.

- Active infection requiring therapy.

- History of interstitial lung disease.

- History of (noninfectious) pneumonitis that required steroids or current pneumonitis.

- Active autoimmune disease that has required systemic treatment in the past 2 years.

Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is

allowed.

- Has known hepatitis B or C infections or known to be positive for hepatitis B surface

antigen (HBsAg)/hepatitis B virus (HBV) deoxyribonucleic acid (DNA) or hepatitis C

antibody or ribonucleic acid (RNA).

- Has a history or current evidence of any condition, therapy, laboratory abnormality,

or other circumstance that might confound the results of the study or interfere with

the participant's participation for the full duration of the study, such that it is

not in the best interest of the participant to participate, in the opinion of the

treating investigator.

- Received prior radiotherapy within 2 weeks of start of study intervention, has

radiation-related toxicities requiring corticosteroids, or had a history of radiation

pneumonitis.

- Has received a live or live-attenuated vaccine within 30 days before the first dose of

study intervention. Administration of killed vaccines are allowed.

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with

an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,

cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137), and was

discontinued from that treatment due to a ≥Grade 3 immune-related AE (irAE).

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of

immunosuppressive therapy within 7 days before the start of study treatment.

- Has had an allogeneic tissue/solid organ transplant in the last 5 years or has

evidence of graft-versus-host disease.

Studien-Rationale

Primary outcome:

1. Number of Participants with a Dose-Limiting Toxicity (DLT) Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 5.0 (Time Frame - Up to approximately 21 days):
DLT is defined as any of the following toxicities, unless assessed by the investigator to be clearly due to the underlying disease or extraneous causes: Grade (Gr) 4 nonhematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Gr 4 thrombocytopenia of any duration; Gr 3 thrombocytopenia associated with clinically significant bleeding; Gr 4 anemia regardless of duration; Nonhematologic AE Gr ≥3 in severity, with exceptions; Any Gr 3 or 4 nonhematologic lab abnormality if clinically significant medical intervention is required, or if leads to hospitalization, persists for >72 hours or results in drug-induced liver injury with exceptions; Gr 3 or 4 febrile neutropenia; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Treatment-related toxicity resulting in study treatment discontinuation during Cycle 1 (C1); Missing >25% of MK-6598 doses as a result of treatment-related AE during C1; Gr 5 toxicity.

2. Number of Participants Who Experience At Least One AE (Time Frame - Up to approximately 27 months):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.

3. Number of Participants Who Discontinue Study Treatment Due to an AE (Time Frame - Up to approximately 24 months):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE will be reported.

Secondary outcome:

1. Area Under the Curve (AUC) of MK-6598 (Time Frame - Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 minutes (min), 45 min, 60 min, 2 hours (hrs), 6 hrs; Days 2 and 9 of Cycle 1: predose; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose):
Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC.

2. Minimum Serum Concentration (Cmin) of MK-6598 (Time Frame - Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs; Days 2 and 9 of Cycle 1: predose; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose):
Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmin

3. Maximum Serum Concentration (Cmax) of MK-6598 (Time Frame - Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs; Days 2 and 9 of Cycle 1: predose; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose):
Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax.

4. Tumor Phenylpyruvate Concentrations (Time Frame - Days 1, 8, and 15 of Cycle 1: predose, postdose at 30 min, 45 min, 60 min, 2 hrs, 6 hrs; Days 2 and 9 of Cycle 1: predose; Day 1 of Cycles 2, 5, 10, 15, 20, 25, 30, and 35: predose):
Blood samples pre-dose and at multiple timepoints post-dose will be used to determine tumor phenylpyruvate concentrations.

Studien-Arme

  • Experimental: MK-6598
    Participants will receive MK-6598 daily (QD) at escalating dose levels from 50-500 mg for up to a total of 35 cycles (up to approximately 24 months).
  • Experimental: MK-6598 + Pembrolizumab
    Participants will receive MK-6598 QD at escalating dose levels from 50-500, plus pembrolizumab 200 mg once every 21-day cycle for up to 35 cycles (up to approximately 24 months).

Geprüfte Regime

  • MK-6598:
    Oral tablet
  • Pembrolizumab (MK-3475 / Keytruda® / ):
    Intravenous (IV) infusion

Quelle: ClinicalTrials.gov


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