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JOURNAL ONKOLOGIE – STUDIE

Evaluation of Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008/KEYSTEP-008)

Rekrutierend

NCT-Nummer:
NCT04895722

Studienbeginn:
Juni 2021

Letztes Update:
11.04.2024

Wirkstoff:
Pembrolizumab, Pembrolizumab/Quavonlimab, Pembrolizumab/Favezelimab, Pembrolizumab/Vibostolimab, MK-4830

Indikation (Clinical Trials):
Colorectal Neoplasms, Microsatellite Instability

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 108)

Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie ( Site 0612)
81737 Muenchen
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 498967942651» Ansprechpartner anzeigen
Otto-von-Guericke-Universität Magdeburg-Klinik für Gastroenterologie, Hepatologie und Infektiologie
39120 Magdeburg
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +493916713100» Ansprechpartner anzeigen
Universitaetsklinikum Carl Gustav Carus Dresden-Medical Dept I - Medical Oncology ( Site 0601)
01307 Dresden
(Sachsen)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +49 351 458 7683» Ansprechpartner anzeigen
Mid Florida Cancer Center ( Site 1519)
32763 Orange City
United StatesAbgeschlossen» Google-Maps
University Cancer & Blood Center, LLC ( Site 1521)
30607 Athens
United StatesAbgeschlossen» Google-Maps
University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P
60637 Chicago
United StatesAbgeschlossen» Google-Maps
Icahn School of Medicine at Mount Sinai ( Site 1528)
10029 New York
United StatesAbgeschlossen» Google-Maps
UPMC Hillman Cancer Center ( Site 1516)
15232 Pittsburgh
United StatesAbgeschlossen» Google-Maps
Vanderbilt University Medical Center-Vanderbilt-Ingram Cancer Center ( Site 1509)
37232 Nashville
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 800-811-8480» Ansprechpartner anzeigen
Baylor Scott & White Medical Center - Temple-Division of Hematology/Oncology ( Site 1549)
76508 Temple
United StatesAbgeschlossen» Google-Maps
Northwest Medical Specialties, PLLC ( Site 1546)
98405 Tacoma
United StatesAbgeschlossen» Google-Maps
Hospital Metropolitano - Sede Lindora-Metropolitano Research Institute Sede Lindora ( Site 2102)
10903 Santa Ana
Costa RicaRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 50684978912» Ansprechpartner anzeigen
Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service d'Hepato-Gastro-Enterologie et
13385 Marseille
FranceAbgeschlossen» Google-Maps
Centre Georges François Leclerc ( Site 0506)
21079 Dijon
FranceAbgeschlossen» Google-Maps
CHU Rangueil-Digestive oncology department ( Site 0502)
31059 Toulouse
FranceAbgeschlossen» Google-Maps
Hopital Claude Huriez - CHU de Lille ( Site 0510)
59037 Lille
FranceAbgeschlossen» Google-Maps
Centre Hospitalier Universitaire de Poitiers ( Site 0511)
86021 Poitiers
FranceAktiv, nicht rekrutierend» Google-Maps
Hôpital Saint Antoine-Oncologie médicale ( Site 0508)
75571 Paris
FranceAktiv, nicht rekrutierend» Google-Maps
Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 0802)
20133 Milan
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +390223903835» Ansprechpartner anzeigen
Istituto Nazionale Tumori IRCCS Fondazione Pascale-Department of Abdominal Oncology ( Site 0803)
80131 Napoli
ItalyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +3908159031775» Ansprechpartner anzeigen
Kyungpook National University Chilgok Hospital-Hematology/oncology ( Site 1103)
41404 Daegu
Korea, Republic ofRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 053-200-3017» Ansprechpartner anzeigen
Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1104)
03722 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +82 (2) 331 2471» Ansprechpartner anzeigen
The Catholic Univ. of Korea Seoul St. Mary's Hospital-Medical Oncology ( Site 1106)
06591 Seoul
Korea, Republic ofRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +82 (2) 331 2471» Ansprechpartner anzeigen
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Onkologii i Radioterapii ( Site
02-034 Warszawa
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 225709223» Ansprechpartner anzeigen
Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 0903)
75-581 Koszalin
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 943488930» Ansprechpartner anzeigen
Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1001)
198255 Saint Petersburg
Russian FederationAbgeschlossen» Google-Maps
Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology-Clinical Pharmacology and Chemotherapy
115478 Moscow
Russian FederationAbgeschlossen» Google-Maps
First Moscow State Medical University I.M. Sechenov-Interhospital Institution Health Management Cl
119991 Moscow
Russian FederationAbgeschlossen» Google-Maps
Rostov Cancer Research Institute ( Site 1014)
344037 Rostov on Don
Russian FederationSchwebend» Google-Maps
GBUZ SPb CRPCstmc(o) ( Site 1005)
197758 Sankt- Peterburg
Russian FederationAbgeschlossen» Google-Maps
Republican Clinical Oncology Dispensary-Chemotherapy #3 ( Site 1006)
420029 Kazan
Russian FederationAbgeschlossen» Google-Maps
TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1305)
34722 Istanbul
TurkeyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +90216 606 52 00» Ansprechpartner anzeigen
UCLH-Cancer Clinical Trials Unit ( Site 1402)
NW1 2PG London-Camden
United KingdomAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

The purpose of this study is to assess the efficacy and safety of co-formulated

pembrolizumab/quavonlimab versus other treatments in participants with MSI-H or dMMR

Metastatic Stage IV Colorectal Cancer.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has a histologically confirmed diagnosis of Stage IV CRC adenocarcinoma (as defined by

American Joint Committee on Cancer [AJCC] version 8)

- Has locally confirmed dMMR/MSI-H

- Has a life expectancy of at least 3 months

- Female participants are eligible to participate if not pregnant or breastfeeding, and

not a woman of childbearing potential (WOCBP), or if a WOCBP then uses a contraceptive

method that is highly effective or is abstinent on a long-term and persistent basis,

during the intervention period and for at least 120 days after the last dose of study

intervention

- Has measurable disease per RECIST 1.1 as assessed by the site and verified by BICR

- Submit an archival (within 5 years of Screening) or newly obtained tumor tissue sample

that has not been previously irradiated; formalin-fixed, paraffin embedded (FFPE)

blocks are preferred to slides.

- Has adequate organ function

Cohort A:

- Has been previously treated for their Stage IV dMMR/MSI-H CRC and radiographically

progressed on or after or could not tolerate standard treatment, which must include all of

the following agents if approved and locally available in the country where the participant

is randomized:

- Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as equivalent

to fluorouracil in prior therapy)

- With or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody

(e.g., bevacizumab)

- At least one of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies

(cetuximab or panitumumab) for rat sarcoma viral oncogene homolog (RAS) wild-type

participants with left-sided tumors. Prior EGFR therapy is optional for patients with

right sided RAS Wild-type (WT) tumors.

Cohort B:

- Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for

this disease

Exclusion Criteria:

- Has received prior therapy with an agent directed to another stimulatory or

coinhibitory T-cell receptor

- Has received prior systemic anticancer therapy including investigational agents within

4 weeks before the first dose of study intervention

- Has not recovered adequately from a surgery procedure, and/or has any complications

from a prior surgery before starting study intervention

- Has received prior radiotherapy within 2 weeks of start of study intervention

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

study intervention

- Is currently participating in or has participated in a study of an investigational

agent or has used an investigational device within 4 weeks before the first dose of

study intervention

- 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 prior to the first dose of study medication

- Has a known additional malignancy that is progressing or has required active treatment

within the past 2 years

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

meningitis

- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, quavonlimab, favezelimab,

vibostolimab, MK-4830, and/or any of their excipients

- Has an active autoimmune disease that has required systemic treatment in past 2 years

(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive

drugs)

- Has a history of (noninfectious) pneumonitis that required steroids or has current

pneumonitis

- Has a history of acute or chronic pancreatitis

- Has neuromuscular disorders associated with an elevated creatine kinase

- Has urine protein ≥1 gram/24 hours

- Has an active infection requiring systemic therapy (e.g., tuberculosis, known viral or

bacterial infections, etc.)

- Has a known history of Human Immunodeficiency Virus (HIV) infection

- Concurrent active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive

and/or detectable Hepatitis B Virus [HBV] deoxyribonucleic acid [DNA]) and Hepatitis C

virus (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid [RNA]

infection

- Has clinically significant cardiac disease, including unstable angina, acute

myocardial infarction within 6 months from Day 1 of study intervention administration,

or New York Heart Association Class III or IV congestive heart failure. Medically

controlled arrhythmia stable on medication is permitted.

- Has present or progressive accumulation of pleural, ascitic, or pericardial fluid

requiring drainage or diuretic drugs within 2 weeks before randomization/allocation

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

that might confound the results of the study, interfere with the participant's

participation for the full duration of the study, or is not in the best interest of

the participant to participate, in the opinion of the treating investigator

- Has a known psychiatric or substance abuse disorder that would interfere with the

participant's ability to cooperate with the requirements of the study

- Has had an allogenic tissue/solid organ transplant

Studien-Rationale

Primary outcome:

1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) (Time Frame - Up to approximately 50 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 RECIST 1.1. ORR as assessed by BICR will be presented.



Secondary outcome:

1. Duration of Response (DOR) per RECIST 1.1 as assessed by BICR (Time Frame - Up to approximately 50 months):
DOR is defined as the time from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until Progressive Disease (PD) or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. 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. DOR as assessed by BICR will be presented.

2. Progression-Free Survival (PFS) per RECIST 1.1 as assessed by BICR (Time Frame - Up to approximately 50 months):
PFS is defined as the time from randomization (or first dose) to the first documented PD per RECIST 1.1 or death from any cause, whichever occurs first. 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. PFS as assessed by BICR will be presented.

3. PFS per RECIST 1.1 as assessed by Investigator (Time Frame - Up to approximately 50 months):
PFS is defined as the time from randomization (or first dose) to the first documented PD per RECIST 1.1 or death from any cause, whichever occurs first. 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. PFS as assessed by investigator will be presented.

4. ORR per RECIST 1.1 as assessed by Investigator (Time Frame - Up to approximately 50 months):
ORR is defined as the percentage of participants who have a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR as assessed by investigator will be presented.

5. DOR per RECIST 1.1 as assessed by Investigator (Time Frame - Up to approximately 50 months):
DOR is defined as the time from the first documented evidence of a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 until PD or death due to any cause, whichever occurs first, in participants demonstrating a CR or PR. 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. DOR as assessed by investigator will be presented.

6. Overall Survival (OS) (Time Frame - Up to approximately 50 months):
OS is defined as the time from randomization (or first dose) to death due to any cause. OS will be presented.

7. Number of Participants Who Experienced an Adverse Event (AE) (Time Frame - Up to approximately 50 months):
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants with an AE will be presented.

8. Number of Participants Discontinuing Study Treatment Due to an AE (Time Frame - Up to approximately 50 months):
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study intervention. The number of participants that discontinue study treatment due to an AE will be presented.

Studien-Arme

  • Active Comparator: Pembrolizumab
    Participants receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years.
  • Experimental: Pembrolizumab/Quavonlimab
    Participants receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years.
  • Experimental: Pembrolizumab/Favezelimab
    Participants receive co-formulated pembrolizumab/favezelimab (200 mg/800 mg) every 3 weeks (Q3W) for up to approximately 2 years.
  • Experimental: Pembrolizumab/Vibostolimab
    Participants receive co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years.
  • Experimental: Pembrolizumab Plus MK-4830
    Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.

Geprüfte Regime

  • Pembrolizumab (MK-3475 / Keytruda® / ):
    400 mg or 200 mg pembrolizumab administered via IV infusion.
  • Pembrolizumab/Quavonlimab (MK-1308A):
    Co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) fixed-dose combination (FDC) administered via IV infusion.
  • Pembrolizumab/Favezelimab (MK-4280A):
    Co-formulated pembrolizumab/favezelimab (200 mg/800 mg) FDC administered via IV infusion
  • Pembrolizumab/Vibostolimab (MK-7684A):
    Co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) FDC administered via IV infusion
  • MK-4830:
    800 mg MK-4830 administered via IV infusion

Quelle: ClinicalTrials.gov


Sie können folgenden Inhalt einem Kollegen empfehlen:

"Evaluation of Co-formulated Pembrolizumab/Quavonlimab (MK-1308A) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer (CRC) (MK-1308A-008/KEYSTEP-008)"

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