Donnerstag, 18. Juli 2024
Navigation öffnen
Anzeige:
Wefra Programatic
 
JOURNAL ONKOLOGIE – STUDIE

A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)

Rekrutierend

NCT-Nummer:
NCT05067283

Studienbeginn:
Dezember 2021

Letztes Update:
21.06.2024

Wirkstoff:
MK-1084, Pembrolizumab, Carboplatin, Pemetrexed, Cetuximab, Oxaliplatin, Leucovorin, 5-Fluorouracil

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 59)

John Theurer Cancer Center at Hackensack University Medical Center ( Site 0260)
07601 Hackensack
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 551-996-5900» Ansprechpartner anzeigen
Laura and Isaac Perlmutter Cancer Center ( Site 0270)
10016 New York
United StatesAbgeschlossen» Google-Maps
Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0032)
M5G 2M9 Toronto
CanadaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 416-946-4501» Ansprechpartner anzeigen
James Lind Centro de Investigación del Cáncer ( Site 0043)
4800827 Temuco
ChileAbgeschlossen» Google-Maps
Southern Medical University Nanfang Hospital-Depatrment of Respiratory and Critical Care Medicine (
510515 Guangzhou
ChinaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 8620 62787110» Ansprechpartner anzeigen
Jilin Cancer Hospital-oncology department ( Site 0412)
132000 Changchun
ChinaAbgeschlossen» Google-Maps
New Zealand Clinical Research (Christchurch) ( Site 0004)
8011 Christchurch
New ZealandAbgeschlossen» Google-Maps
Centro Hemato Oncológico Paitilla ( Site 0163)
0832-00752 Panama City
PanamaAbgeschlossen» Google-Maps
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 0170
02-781 Warszawa
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 48225463381» Ansprechpartner anzeigen
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0173)
75-581 Koszalin
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 48502204953» Ansprechpartner anzeigen
Hospital Universitario Fundación Jiménez Díaz-START Madrid-FJD ( Site 0211)
28040 Madrid
SpainRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 0034 91 550 48 00 ext 2689» Ansprechpartner anzeigen
Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 0445)
83301 Kaohsiung Niao Sung Dist
TaiwanRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +886773171233267» Ansprechpartner anzeigen
Erciyes University ( Site 0232)
38039 Talas
TurkeyAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This is a study evaluating the safety, pharmacokinetics, and efficacy of MK-1084 alone, and

MK-1084 plus other combination therapies in participants with advanced solid tumors with

identified kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation.

Ein-/Ausschlusskriterien

Inclusion Criteria:

For all participants:

- Has measurable disease by RECIST 1.1 criteria

- Has adequate organ function

- Male participants must be abstinent from heterosexual intercourse as their preferred

and usual lifestyle (abstinent on a long-term and persistent basis) and agree to

remain abstinent OR must agree to use contraception unless confirmed to be azoospermic

- Female participants must not be pregnant or breastfeeding, and at least one of the

following conditions applies: is not a woman of child-bearing potential (WOCBP); is a

WOCBP and uses a contraceptive method that is highly effective, with low user

dependency, or be abstinent from heterosexual intercourse as their preferred and usual

lifestyle and must have a negative highly sensitive pregnancy test within 24 hours

(for a urine test) or 72 hours (for a serum test) before the first dose of study

intervention

For Arm 1 - Has locally advanced unresectable or metastatic solid-tumor malignancy with

histologically OR blood-based confirmation of KRAS G12C mutation who has received at least

1 line of therapy for systemic disease

For Arm 2

- Has an untreated metastatic non-small cell lung cancer (NSCLC) with histologically OR

blood-based confirmation of KRAS G12C mutation and histologic confirmation of programmed

cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥1%

For Arm 3

- Has locally advanced unresectable or metastatic solid-tumor malignancy with

histologically or blood-based confirmation of KRAS G12C mutation who has received at

least 1 line of therapy for systemic disease Expansion Group A: 3L/4L metastatic

colorectal cancer (mCRC)

- Has histologically or cytologically confirmed diagnosis of unresectable and metastatic

colorectal adenocarcinoma with histological or blood-based confirmation of KRAS G12C

mutation

- Previous treatment failure of 2 or 3 previous lines of systemic therapy Expansion

Group B

- Has locally advanced unresectable or metastatic solid-tumor malignancy, excluding

NSCLC or CRC, with histologically or blood- based confirmation of KRAS G12C mutation

who has received at least 1 line of therapy for systemic disease

Arm 4 only - Has an untreated advanced or metastatic nonsquamous NSCLC with histologically

or blood-based confirmation of KRAS G12C mutation

Arm 5 only

- Histologically or cytologically confirmed diagnosis of locally advanced unresectable

or metastatic colorectal adenocarcinoma and with histologically or blood-based

confirmation of KRAS G12C mutation

- Previous treatment failure of one or 2 previous line(s) of systemic therapy

Arm 6 only

- Locally advanced unresectable or metastatic colorectal adenocarcinoma with histologically

or blood-based confirmation of KRAS G12C mutation

Exclusion Criteria:

- Has received chemotherapy, definitive radiation, or biological cancer therapy within 4

weeks (2 weeks for palliative radiation) before first dose of study intervention

- Has a history of second malignancy, unless potentially curative treatment has been

completed with no evidence of malignancy for 5 years

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

meningitis

- Has an active infection requiring systemic therapy

- Known history of HIV infection or. has a known history of Hepatitis B virus or known

active Hepatitis C virus infection

- Has a history of interstitial lung disease, noninfectious pneumonitis requiring active

steroid therapy, or ongoing pneumonitis

- Has an active autoimmune disease requiring systemic therapy

- Has not fully recovered from any effects of major surgical procedure without

significant detectable infection

- Has one or more of the following ophthalmological findings/conditions: intraocular

pressure >21 mm Hg and/or any diagnosis of glaucoma; diagnosis of central serous

retinopathy, retinal vein occlusion, or retinal artery occlusion and/or a diagnosis of

retinal degenerative disease

- Has received live or live-attenuated vaccine within 4 weeks of study start

Arm 4 Only

- Is unable to interrupt aspirin or other nonsteroidal anti-inflammatories (NSAIDs),

other than an aspirin dose ≤1.3 grams per day, for at least 2 days (5 days for

long-acting agents [for example, piroxicam]) before, during, and for at least 2 days

after administration of pemetrexed.

- Is unable/unwilling to take folic acid, vitamin B12, and dexamethasone

Studien-Rationale

Primary outcome:

1. Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) (Time Frame - Up to ~21 days):
A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT will be reported.

2. Number of Participants Who Experience an Adverse Event (AE) (Time Frame - Up to ~56 months):
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be reported.

3. Number of Participants Who Discontinue Study Treatment Due to an AE (Time Frame - Up to ~56 months):
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be reported.

Secondary outcome:

1. Objective Response Rate (ORR) (Time Frame - Up to ~56 months):
ORR is defined as the percentage of participants who have 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) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1). The percentage of participants who experience a CR or PR as assessed by the investigator based on RECIST 1.1 will be reported.

2. Duration of Response (DOR) (Time Frame - Up to ~56 months):
DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. The DOR as assessed by the investigator will be reported.

3. Mean Plasma Concentration of MK-1084 (Time Frame - At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)):
Mean Plasma Concentration of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.

4. Maximum Concentration (Cmax) of MK-1084 (Time Frame - At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6).):
Cmax of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.

5. Time to Maximum Concentration (Tmax) of MK-1084 (Time Frame - At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)):
Tmax of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.

6. Minimum Concentration (Cmin) of MK-1084 (Time Frame - At designated timepoints during the study in Cycles 1, 2, 3, 5, 9, 13, 17, 21, 25, and every 6 weeks thereafter up to 56 months. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)):
Cmin of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.

7. Area Under the Concentration Time-Curve 0-12 Hours (AUC 0-12) of MK-1084 (Time Frame - At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 12 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)):
AUC 0-12 of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.

8. Area Under the Concentration Time-Curve 0-24 Hours (AUC 0-24) of MK-1084 (Time Frame - At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 24 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)):
AUC 0-24 of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.

9. Half-Life (t1/2) of MK-1084 (Time Frame - At designated timepoint during the study in Cycle 1 Day 1: Predose and up to 24 hours postdose. Cycle=3 weeks (Arms 1-4) and 4 weeks (Arms 5-6)):
Half-Life (t1/2) of MK-1084 determined by blood samples collected pre-dose and at designated timepoints post-dose will be reported.

Studien-Arme

  • Experimental: Arm 1
    Participants will receive daily oral escalating doses of up to 800 mg of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.
  • Experimental: Arm 2
    Participants will receive MK-1084 daily oral escalating dose of up to 800 mg plus pembrolizumab given as a 200 mg intravenous infusion once every 21-day cycle up to a total of 35 cycles (up to ~24 months). Treatment with MK-1084 will continue until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.
  • Experimental: Arm 3
    Participants will receive alternate formulation of MK-1084 until progressive disease or discontinuation. Dosing regimen may be adjusted based on safety.
  • Experimental: Arm 4
    Participants will receive MK-1084 daily oral dose plus an intravenous infusion of pembrolizumab (200 mg) once every 21-day cycle for up to 35 cycles (up to ~24 months). Participants will also receive carboplatin (per label) and pemetrexed (per label) once every 21-day cycle for the first 4 cycles.
  • Experimental: Arm 5
    Participants will receive MK-1084 daily oral dose plus an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle.
  • Experimental: Arm 6
    Participants will receive MK-1084 daily oral dose. Additionally, participants receive an intravenous infusion of cetuximab (per label) every 2 weeks of each 28-day cycle, oxaliplatin (per label) for first 6 cycles, and leucovorin (per label) and 5-fluorouracil (per label) once every 14-days.

Geprüfte Regime

  • MK-1084:
    Oral dose
  • Pembrolizumab (KEYTRUDA® / MK-3475 / ):
    Intravenous infusion of 200 mg
  • carboplatin:
    Per label
  • pemetrexed:
    Per label
  • cetuximab:
    Per label
  • oxaliplatin:
    Per label
  • leucovorin:
    Per label
  • 5-fluorouracil:
    Per label

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"A Study of MK-1084 in KRAS Mutant Advanced Solid Tumors (MK-1084-001)"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!

Die Verwendung Ihrer Daten für den Newsletter können Sie jederzeit mit Wirkung für die Zukunft gegenüber der MedtriX GmbH - Geschäftsbereich rs media widersprechen ohne dass Kosten entstehen. Nutzen Sie hierfür etwaige Abmeldelinks im Newsletter oder schreiben Sie eine E-Mail an: rgb-info[at]medtrix.group.