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JOURNAL ONKOLOGIE – STUDIE

A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)

Rekrutierend

NCT-Nummer:
NCT04586231

Studienbeginn:
Februar 2021

Letztes Update:
07.06.2021

Wirkstoff:
Belzutifan, Lenvatinib, Cabozantinib

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Renal Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
Eisai Inc.

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 29)

AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 0003)
32804 Orlando
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: 407-303-2024
» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

Brief Summary:

This study will compare the efficacy and safety of belzutifan + lenvatinib versus

cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell

component after prior therapy.

The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms

of progression-free survival or overall survival.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).

- Disease progression on or after having received systemic treatment with

anti-programmed cell death-1/ligand 1 (PD-1/L1) for locally advanced or metastatic

RCC.

- Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.

- Karnofsky performance status (KPS) score of at least 70% assessed within 10 days

before randomization.

- Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy

of a tumor lesion not previously irradiated.

- Received no more than 2 prior systemic regimens for locally advanced or metastatic

RCC.

- Received only 1 prior antiPD-1/L1 therapy for locally advanced or metastatic RCC.

- A male participant is eligible to participate if he is abstinent from heterosexual

intercourse or agrees to use contraception during the intervention period and for at

least 7 days after the last dose of belzutifan or lenvatinib in the

belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of

cabozantinib.

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

breastfeeding, and at least 1 of the following conditions applies: Not a woman of

childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive

guidance during the intervention period and for at least 30 days after the last dose

of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last

dose of study intervention in the cabozantinib arm.

- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within

24 hours before the first dose of study intervention.

- Adequately controlled blood pressure.

- Adequate organ function.

Exclusion Criteria:

- Is a WOCBP who has a positive urine pregnancy test within 24 hours before the first

dose of study intervention.

- Hypoxia (pulse oximeter reading <92% at rest), requires intermittent supplemental

oxygen, or requires chronic supplemental oxygen.

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

within the past 3 years except for basal cell carcinoma of the skin, squamous cell

carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in

situ) that have undergone potentially curative therapy.

- Known central nervous system (CNS) metastases and/or carcinomatous meningitis.

- Clinically significant cardiac disease within 6 months of first dose of study

intervention.

- Prolongation of QTc interval to >480 ms.

- Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not

clinically stable.

- Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.

- Moderate to severe hepatic impairment.

- History of significant bleeding within 3 months before randomization.

- History of solid organ transplantation.

- Known psychiatric or substance abuse disorder that would interfere with cooperation

with the requirements of the study.

- Unable to swallow orally administered medication or has a gastrointestinal disorder

affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).

- Known hypersensitivity or allergy to the active pharmaceutical ingredients or any

component of the study intervention formulations.

- Received colony-stimulating factors [eg, granulocyte colony-stimulating factor

(G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant

erythropoietin (EPO)] within 28 days before randomization.

- Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α

inhibitor.

- Prior treatment with lenvatinib.

- Prior treatment with cabozantinib.

- Currently participating in a study of an investigational agent or using an

investigational device.

- Active infection requiring systemic therapy.

- History of human immunodeficiency virus (HIV) infection.

- History of hepatitis B or known active hepatitis C infection.

- 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.

Studien-Rationale

Primary outcome:

1. Progression-Free Survival (PFS) 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 34 months):
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥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 ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review will be presented.

2. Overall Survival (OS) (Time Frame - Up to approximately 44 months):
OS is defined as time from randomization to death due to any cause.

Secondary 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 24 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. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.

2. Duration of Response (DOR) 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 44 months):
For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR as assessed by blinded independent central review will be presented.

3. Number of Participants Who Experienced One or More Adverse Events (AEs) (Time Frame - Up to approximately 44 months):
An adverse event (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.

4. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) (Time Frame - Up to approximately 44 months):
An adverse event (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.

Studien-Arme

  • Experimental: Belzutifan + Lenvatinib
    Belzutifan 120 mg and lenvatinib 20 mg orally once a day
  • Active Comparator: Cabozantinib
    Cabozantinib 60 mg orally once a day

Geprüfte Regime

  • Belzutifan (PT2977 / MK-6482 / ):
    Immediate-release 40 mg tablet
  • Lenvatinib (Lenvima / E7080 / MK-7902 / ):
    Capsule available in 4 mg and 10 mg dosages
  • Cabozantinib (Cabometyx / Cometriq / XL184 / BMS-907351 / ):
    Tablet available in 20 mg, 40 mg and 60 mg dosages

Quelle: ClinicalTrials.gov


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