A clinical study of belzutifan for treatment of kidney cancer (MK-6482-013)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Dec 2020 → ongoing

Decision date (initial)

2023-09-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502123-21-00

EudraCT number

2020-001907-18

WHO UTN

U1111-1283-3731

ClinicalTrials.gov

NCT04489771

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Pharmacogenomic, Safety, Pharmacodynamic, Pharmacokinetic, Pharmacogenetic

To compare the 120 mg once daily (QD) dose and 200 mg QD dose of belzutifan with respect to objective response rate (ORR) based on Response Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR)

Secondary objectives 6

1. To evaluate the 120 mg QD dose and 200 mg QD dose of belzutifan with respect to progression-free survival (PFS) as assessed by BICR according to RECIST 1.1
2. To evaluate the 120 mg QD dose and 200 mg QD dose of belzutifan with respect to duration of response (DOR) as assessed by BICR according to RECIST 1.1
3. To evaluate the 120 mg QD dose and 200 mg QD dose of belzutifan with respect to clinical benefit rate (CBR) as assessed by BICR according to RECIST 1.1
4. To evaluate the 120 mg QD dose and 200 mg QD dose of belzutifan with respect to overall survival (OS)
5. To evaluate the safety and tolerability of the 120 mg QD dose compared with the 200 mg QD dose of belzutifan
6. To evaluate the pharmacokinetics (PK) of the 120 mg QD dose and 200 mg QD dose of belzutifan administered orally as monotherapy

Conditions and MedDRA coding

Advanced Renal Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Has a histologically confirmed diagnosis of locally advanced/metastatic renal cell carcinoma (RCC) with clear cell component
2. Can submit an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
3. Has experienced disease progression on or after systemic treatment with an anti-programmed cell death 1 (PD-1)/Ligand 1 (L1) therapy for locally advanced or metastatic RCC
4. Has received no more than 3 prior systemic regimens for locally advanced or metastatic RCC
5. Has recovered from all AEs due to previous therapies to ≤Grade 1 or baseline, with the exception of ≤Grade 2 neuropathy or endocrine-related AEs ≤Grade 2 requiring treatment or hormone replacement

Exclusion criteria 14

1. Has hypoxia (a pulse oximeter reading <92% at rest), requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
2. Has a 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 [e.g., breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy
3. Has known CNS metastases and/or carcinomatous meningitis
4. Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction ≤6 months from Day 1 of study drug administration or New York Heart Association Class III or IV congestive heart failure
5. Has moderate to severe hepatic impairment (Child-Pugh B or C)
6. Has received any type of small molecule kinase inhibitor (including investigational kinase inhibitor) ≤2 weeks before randomization
7. Has received any type of systemic anticancer antibody (including investigational antibody) ≤4 weeks before randomization
8. Has received prior radiotherapy ≤2 weeks prior to first dose of study intervention. Participants must have recovered from all radiation-related toxicities and not require corticosteroids
9. Has had major surgery ≤3 weeks prior to first dose of study intervention
10. Has an active infection requiring systemic therapy
11. Has active tuberculosis (TB)
12. Has a diagnosis of immunodeficiency
13. Has a known history of human immunodeficiency virus (HIV) infection
14. Has a known history of hepatitis B (HBV) or known active hepatitis C (HCV) infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

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)

Secondary endpoints 8

1. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
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)
3. Clinical Benefit Rate (CBR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
4. Overall Survival (OS)
5. Number of Participants Who Experience One or More Adverse Events (AEs)
6. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
7. Maximum Plasma Concentration (Cmax) of belzutifan
8. Trough Plasma Concentration (Ctrough) of belzutifan

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ding Wang

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ding Wang

Third parties 7

Locations

4 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 69 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications