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JOURNAL ONKOLOGIE – STUDIE

Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02)

Rekrutierend

NCT-Nummer:
NCT04305054

Studienbeginn:
Juli 2020

Letztes Update:
07.03.2024

Wirkstoff:
Pembrolizumab, Lenvatinib, Vibostolimab, Pembrolizumab/Quavonlimab, Favezelimab/Pembrolizumab, ATRA

Indikation (Clinical Trials):
Melanoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Merck Sharp & Dohme LLC

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme LLC

Kontakt

Studienlocations
(3 von 53)

Providence Saint John's Health Center ( Site 2010)
90404 Santa Monica
United StatesAbgeschlossen» Google-Maps
NYU Clinical Cancer Center ( Site 2002)
10016 New York
United StatesAbgeschlossen» Google-Maps
Duke Cancer Institute ( Site 2005)
27710 Durham
United StatesAbgeschlossen» Google-Maps
Oregon Health & Science University ( Site 2013)
97239 Portland
United StatesAbgeschlossen» Google-Maps
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
02-781 Warszawa
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 48225462031
» Ansprechpartner anzeigen
HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit
08036 Barcelona
SpainRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +34932275402
» Ansprechpartner anzeigen
CHUV Centre Hospitalier Universitaire Vaudois ( Site 2602)
1011 Lausanne
SwitzerlandAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

Substudy 02B is part of a larger research study that is testing experimental treatments for

melanoma, a type of skin cancer. The larger study is the umbrella study.

The goal of substudy 02B is to evaluate the safety and efficacy of investigational treatment

arms in participants with 1L advanced melanoma and to identify the investigational agent(s)

that, when used in combination, are superior to the current treatment options/pembrolizumab

monotherapy.

Arm 1: Pembrolizumab + Vibostolimab was added in the base protocol on 13-Nov-2019, and

enrollment into this arm has been completed. Arm 2: Pembrolizumab was added in the base

protocol on 13-Nov-2019, and enrollment stopped prematurely on 15-Aug-2022. Arm 3:

Coformulation Pembrolizumab/Quavonlimab was added in Amendment 01 on 20-Oct-2020, and

enrollment stopped prematurely on 15-Aug-2022. Arm 4: Coformulation Pembrolizumab/Quavonlimab

+ Lenvatinib was added in Amendment 01 on 20-Oct-2020, and enrollment is ongoing. Arm 5:

Coformulation Favezelimab/Pembrolizumab, Arm 6: Coformulation Favezelimab/Pembrolizumab +

All-trans Retinoic Acid (ATRA), and Arm 7: Coformulation Favezelimab/Pembrolizumab +

Vibostolimab were added in Amendment 04 on 10-May-2023, and enrollment for these arms will be

initiated in July 2023.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has histologically or cytologically confirmed melanoma

- Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy

- Has been untreated for advanced disease.

- Has provided a tumor biopsy

- If capable of producing sperm, male participants agree to the following during the

intervention period and for at least the time needed to eliminate each study

intervention after the last dose of study intervention (7 days):

- Abstains from penile-vaginal intercourse as their preferred and usual lifestyle

(abstinent on a long-term and persistent basis) and agrees to remain abstinent OR

- Uses contraception unless confirmed to be azoospermic

- A female participant is eligible to participate if she is not pregnant or

breastfeeding, and at least one of the following conditions applies:

- Is not a WOCBP OR

- Is a WOCBP and Uses a contraceptive method that is highly effective, with low

user dependency, or be abstinent from penile-vaginal intercourse as their

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

during the intervention period and for at least the time needed to eliminate each

study intervention after the last dose of study intervention. The length of time

required to continue contraception for each study intervention is:

- MK-4280A: 120 days

- MK-1308A: 120 days

- MK-7684: 50 days

- MK-3475: 120 days

- Lenvatinib: 30 days

- ATRA: 30 days

- Has adequate organ function

- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less

(except alopecia and Grade 2 neuropathy)

Exclusion Criteria:

- Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7

days before the first dose of study intervention

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

within the past 2 years

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

- Has ocular or mucosal melanoma

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

years

- Has an active infection requiring systemic therapy

- Has known history of human immunodeficiency virus (HIV)

- Has history of Hepatitis B or known Hepatitis C virus infection

- Has a history of (noninfectious) pneumonitis

- Has a history of active tuberculosis (TB)

- Has received prior systemic anticancer therapy within 4 weeks prior to randomization

- Has received prior radiotherapy within 2 weeks of first dose of study intervention

- Has had major surgery <3 weeks prior to first dose of study intervention

- Has received a live vaccine within 30 days before the first dose of study intervention

- Has participated in a study of an investigational agent within 4 weeks prior to the

first dose of study intervention

- Has had an allogeneic tissue/solid organ transplant

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

requirements of the study

- Participants who receive lenvatinib have the following additional exclusion criteria:

- Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula

- Has radiographic evidence of encasement of invasion of a major blood vessel, or

of intratumoral cavitation

- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to

the first dose of study intervention

- Has clinically significant cardiovascular disease within 12 months from first

dose of study intervention

- Has urine protein ≥1 g/24-hour.

- Has presence of gastrointestinal condition including malabsorption,

gastrointestinal anastomosis, or any other condition that might affect the

absorption of lenvatinib

Studien-Rationale

Primary outcome:

1. Percentage of participants who experience a dose-limiting toxicity (DLT): Safety lead-in phase (Time Frame - Up to ~3 weeks):
The percentage of participants who experience 1 or more protocol-defined DLTs during the safety lead-in period will be reported.

2. Percentage of participants who experience an adverse event (AE): Safety lead-in (Time Frame - Up to ~3 weeks):
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. The percentage of participants who experience an AE during the safety lead-in period will be reported.

3. Percentage of participants who discontinue study treatment due to an AE: Safety lead-in (Time Frame - Up to ~3 weeks):
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. The percentage of participants who discontinue study treatment due to an AE during the safety lead-in will be reported.

4. Percentage of participants who experience an adverse event (AE) (Time Frame - Up to ~28 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. The percentage of participants who experience an AE will be reported.

5. Percentage of participants who discontinue study treatment due to an AE (Time Frame - Up to ~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. The percentage of participants who discontinue study treatment due to an AE will be reported.

6. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) (Time Frame - Up to ~30 months):
ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Secondary outcome:

1. Duration of Response (DOR) per RECIST 1.1 (Time Frame - Up to ~30 months):
For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

Studien-Arme

  • Experimental: Pembrolizumab + Vibostolimab
    Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
  • Active Comparator: Pembrolizumab
    Participants will receive pembrolizumab IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.
  • Experimental: Coformulation Pembrolizumab/Quavonlimab
    Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.
  • Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib
    Participants will receive coformulation of pembrolizumab and quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.
  • Experimental: Coformulation Favezelimab/Pembrolizumab
    Participants will receive cofomulation of favezelimab + pembrolizumab (MK-4280A) IV at specified dose on specified days every 3 weeks (Q3W) for up to approximately 2 years
  • Experimental: Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA)
    Participants will receive coformulation of favezelimab and pembrolizumab IV Q3W for up to 35 cycles, plus ATRA orally (for 3 days surrounding each infusion of MK-4280A, including Days 1, 2, and 3 of Cycle 1 and on Days -1, 1, and 2 of all subsequent cycles).
  • Experimental: Coformulation Favezelimab/Pembrolizumab + Vibostolimab
    Participants will receive coformulation of favezelimab and pembrolizumab (MK-4280A) IV and vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Geprüfte Regime

  • Pembrolizumab (MK-3475 / KEYTRUDA® / ):
    Administered via IV infusion at a specified dose on specified days
  • Vibostolimab (MK-7684):
    Administered via IV infusion at a specified dose on specified days
  • Pembrolizumab/Quavonlimab (MK-1308A):
    Administered via IV infusion at a specified dose on specified days
  • Lenvatinib (MK-7902 / E7080 / LENVIMA® / ):
    Administered via oral capsule at a specified dose on specified days
  • Favezelimab/Pembrolizumab (MK-4280A):
    Administered via IV infusion at a specified dose on specified days
  • ATRA:
    Administered via oral capsule at a specified dose on specified days

Quelle: ClinicalTrials.gov


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