Phase 3 Study of Belzutifan in Combination With Lenvatinib Versus Cabozantinib for Treatment of RCC

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

19 Apr 2021 → ongoing

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC · Eisai

External identifiers

EU CT number

2024-510620-39-00

EudraCT number

2020-002075-35

WHO UTN

U1111-1302-2815

ClinicalTrials.gov

NCT04586231

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To compare belzutifan+lenvatinib to cabozantinib with respect to PFS per Response Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR).
2. To compare belzutifan+lenvatinib to cabozantinib with respect to OS.

Secondary objectives 3

1. To compare belzutifan+lenvatinib to cabozantinib with respect to objective response rate (ORR) based on RECIST 1.1 as assessed by BICR.
2. To evaluate the duration of response (DOR) as assessed by BICR according to RECIST 1.1.
3. To evaluate the safety and tolerability of belzutifan+lenvatinib compared to cabozantinib.

Conditions and MedDRA coding

Advanced RCC with clear cell component

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).
2. Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose.
3. Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.
4. Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.
5. Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease
6. Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC.
7. 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.
8. A female participant is eligible to participate if they are 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.
9. Adequately controlled blood pressure.
10. Adequate organ function.

Exclusion criteria 21

1. A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.
2. 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.
3. Known central nervous system (CNS) metastases and/or carcinomatous meningitis.
4. Clinically significant cardiac disease within 6 months of first dose of study intervention.
5. Prolongation of QTc interval to >480 ms.
6. Symptomatic pleural effusion (e.g., cough, dyspnea, pleuritic chest pain) that is not clinically stable.
7. Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula.
8. Moderate to severe hepatic impairment.
9. History of significant bleeding within 3 months before randomization.
10. History of solid organ transplantation.
11. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
12. Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).
13. Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.
14. 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.
15. Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2α inhibitor.
16. Prior treatment with lenvatinib.
17. Prior treatment with cabozantinib.
18. Currently participating in a study of an investigational agent or using an investigational device.
19. Active infection requiring systemic therapy.
20. History of human immunodeficiency virus (HIV) infection.
21. History of hepatitis B or known active hepatitis C infection.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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)
2. Overall Survival (OS)

Secondary endpoints 4

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)
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. Number of Participants Who Experienced One or More Adverse Events (AEs)
4. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

Investigational products

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

Test 3

Comparator 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, P. O. Box 2000 P. O. Box 2000

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 6

Locations

13 EU/EEA countries · 69 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 120 files

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

Application history

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