Dienstag, 27. Juli 2021
Navigation öffnen
Anzeige:
Lenvima
Lenvima
 
JOURNAL ONKOLOGIE – STUDIE

Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/KEYMAKER-U02)

Rekrutierend

NCT-Nummer:
NCT04305041

Studienbeginn:
Juni 2020

Letztes Update:
22.07.2021

Wirkstoff:
Pembrolizumab, Lenvatinib, Vibostolimab, Quavonlimab

Indikation (Clinical Trials):
Melanoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
-

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 30)

Oregon Health & Science University ( Site 1013)
97239 Portland
United StatesAbgeschlossen» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

Substudy 02A 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 02A is to evaluate the safety and efficacy of investigational treatment

arms in participants with PD-1 refractory melanoma to identify the investigational agent(s)

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

control available.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has histologically or cytologically confirmed melanoma

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

- Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb)

administered either as monotherapy, or in combination with other therapies

- Has submitted prestudy imaging

- Has not received more than 3 lines of therapy for their advanced melanoma

- Has provided a tumor biopsy

- Male participants who receive lenvatinib are abstinent from heterosexual intercourse

or agree to use contraception during the intervention period and for at least 7 days

after the last dose of lenvatinib; for male participants who only receive

pembrolizumab, quavonlimab, vibostolimab, or a combination, no contraception measures

are needed

- Female participant are not pregnant or breastfeeding and are either not a woman of

child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective

or are abstinent from heterosexual intercourse during the intervention period and for

at least 120 days after the last dose of pembrolizumab, quavonlimab, vibostolimab or

30 days after the last dose of lenvatinib, whichever occurs last

- Has adequate organ function

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

(except alopecia)

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 known hypersensitivity including previous clinically significant hypersensitivity

reaction to treatment with another mAb

- 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 known history of hepatitis B

- 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 pre-existing Grade ≥3 gastrointestinal fistula or nongastrointestinal fistula

- Has radiographic evidence of encasement of invasion of 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

Studien-Rationale

Primary outcome:

1. 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.

2. 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.

3. 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 + Quavonlimab + Vibostolimab
    Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
  • Experimental: Pembrolizumab + Quavonlimab + Lenvatinib
    Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally 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
  • Quavonlimab (MK-1308):
    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
  • Lenvatinib (MK-7902 / LENVIMA® / ):
    Administered via oral capsules at a specified dose on specified days

Quelle: ClinicalTrials.gov


Das könnte Sie auch interessieren
EHA 2021
  • SCD: Häufigere und längere VOC-bedingte Krankenhausaufenthalte nach Vorgeschichte von VOC-Hospitalisierungen – Ergebnisse einer Beobachtungsstudie
  • Real-World-Daten des ERNEST-Registers untermauern Überlebensvorteil unter Ruxolitinib bei primärer und sekundärer Myelofibrose
  • I-WISh-Studie: Ärzte sehen TPO-RAs als beste Option, um anhaltende Remissionen bei ITP-Patienten zu erzielen
  • Phase-III-Studie REACH2 bei steroidrefraktärer akuter GvHD: Hohes Ansprechen auf Ruxolitinib auch nach Crossover
  • SCD: Neues digitales Schmerztagebuch zur tagesaktuellen Erfassung von VOCs wird in Beobachtungsstudie geprüft
  • Französische Real-World-Studie: Eltrombopag meist frühzeitig nach ITP-Diagnose im Rahmen eines Off-label-Use eingesetzt
  • Fortgeschrittene systemische Mastozytose: Französische Real-World-Studie bestätigt klinische Studiendaten zur Wirksamkeit von Midostaurin
  • CML-Management weitgehend leitliniengerecht, aber verbesserungsfähig – Ergebnisse einer Querschnittsbefragung bei britischen Hämatologen
  • Britische Real-World-Studie: Kardiovaskuläres Risikomanagement bei MPN-Patienten in der Primärversorgung nicht optimal
  • Myelofibrose: Früher Einsatz von Ruxolitinib unabhängig vom Ausmaß der Knochenmarkfibrose