Phase 3 study of belzutifan plus pembrolizumab as adjuvant treatment in renal cell carcinoma (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

17 Nov 2023 → ongoing

Decision date (initial)

2023-11-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-505023-31-00

EudraCT number

2021-003436-92

WHO UTN

U1111-1290-7346

ClinicalTrials.gov

NCT05239728

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To compare disease-free survival (DFS) as assessed by investigator for participants treated with belzutifan plus pembrolizumab versus those receiving placebo plus pembrolizumab

Secondary objectives 4

1. To compare overall survival (OS) for participants treated with belzutifan plus pembrolizumab versus those receiving placebo plus pembrolizumab
2. To compare the safety and tolerability profiles for participants treated with belzutifan plus pembrolizumab versus those receiving placebo plus pembrolizumab
3. To compare measures of disease recurrence-specific survival (DRSS) as assessed by the investigator, in participants treated with belzutifan plus pembrolizumab versus those receiving placebo plus pembrolizumab
4. To compare participants treated with belzutifan plus pembrolizumab versus those receiving placebo plus pembrolizumab with respect to mean change from baseline in health-related quality of life (HRQoL) and symptoms using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life 30 Questionnaire (QLQ-C30) and the Functional Assessment of Cancer Therapy –Kidney Symptom Index Disease-related Symptoms (FKSI-DRS)

Conditions and MedDRA coding

Renal cell carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has histologically or cytologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell component per American Joint Committee on Cancer (AJCC) (8th Edition), with or without sarcomatoid features
2. Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node metastasis and tumor grading: (1) Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, any grade, N0, M0 (2) High risk RCC: pT4, any grade N0, M0; pT any stage, any Grade N+, M0 (3) M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤2 years from nephrectomy (metachronous)
3. Has undergone complete resection of the primary tumor (partial or radical nephrectomy) and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants
4. Must have undergone a nephrectomy and/or metastasectomy ≤12 weeks prior to randomization
5. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days before randomization
6. Male participants must agree to continue contraception at least 7 days after the last dose of belzutifan/placebo
7. Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of pembrolizumab or at least 30 days after last dose of belzutifan/placebo, whichever occur last
8. Has adequate organ function

Exclusion criteria 15

1. Has had a major surgery, other than nephrectomy plus resection of preexisting metastases for M1 NED participants, within 4 weeks prior to randomization
2. Has a pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
3. Has clinically significant cardiovascular disease within 6 months from first dose of study intervention
4. Has other clinically significant disorders such as: serious active nonhealing wound/ulcer/bone fracture; requirement for hemodialysis or peritoneal dialysis
5. Has preexisting brain or bone metastatic lesions
6. Has received prior systemic therapy for RCC
7. Has received prior radiotherapy for RCC
8. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention; administration of killed vaccines are allowed
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
10. Has a known additional malignancy (other than RCC treated with nephrectomy and/or metastasectomy) that is progressing or has required active treatment within the past 3 years
11. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy is allowed
12. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
13. Has an active infection, requiring systemic therapy
14. Has a known history of human immunodeficiency virus (HIV) infection, a known history of hepatitis B or known active Hepatitis C virus infection
15. Has had an allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-Free Survival (DFS)

Secondary endpoints 9

1. Overall Survival (OS)
2. Number of Participants Who Experience At Least One Adverse event (AE)
3. Number of Participants Who Discontinue Study Treatment Due to an AE
4. Disease Recurrence-Specific Survival 1 (DRSS1)
5. Disease Recurrence-Specific Survival 2 (DRSS2)
6. Change From Baseline in Health-Related Quality-of-Life (HRQoL) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Items 29 and 30 Score
7. Change From Baseline in Physical Functioning Using the EORTC QLQ-C30 Items 1- 5 Score
8. Change From Baseline in Role Functioning Using the EORTC QLQ-C30 Items 6 and 7 Score
9. Change From Baseline in Disease Symptoms Using the Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score

Investigational products

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

Test 2

Placebo 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

Manish Sharma, MD

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Manish Sharma, MD

Third parties 5

Locations

14 EU/EEA countries · 101 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 14 · Art. 38 CTR

Results and documents

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

Documents 140 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