An Open-label, Randomized Phase 3 Study of Immune and Targeted Combination Therapies, as First-line Treatment in Participants with Advanced clear cell renal cell carcinoma (ccRCC)

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

11 May 2021 → ongoing

Decision date (initial)

2023-08-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

EISAI · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-502122-41-00

EudraCT number

2020-002216-52

WHO UTN

U1111-1283-3681

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1.To compare the Arm A to the Arm C with respect to 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.To compare the Arm A to the Arm C with respect to Overall Survival (OS).
3.To compare the Arm B to the Arm C with respect to PFS per RECIST 1.1 as assessed by BICR.
4.To compare the Arm B to the Arm C with respect to OS.

Secondary objectives 3

1. To compare the Arm A and Arm B to the Arm C with respect to Objective Response Rate (ORR) per 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 the Arm A and Arm B compared to the Arm C.

Conditions and MedDRA coding

Clear cell renal cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Has histologically confirmed diagnosis of RCC with clear cell component
2. Has received no prior systemic therapy for advanced ccRCC
3. Male participants are abstinent from heterosexual intercourse or agree to use contraception during and for at least 7 days after last dose of study intervention with belzutifan and lenvatinib
4. Female participants 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 pembrolizumab or pembrolizumab/quavonlimab or for at least 30 days after last dose of lenvatinib or belzutifan, whichever occurs last
5. Has adequately controlled blood pressure with or without antihypertensive medications
6. Has adequate organ function.
7. Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks prior to randomization/allocation

Exclusion criteria 20

1. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
2. Has had major surgery, other than nephrectomy within 4 weeks prior to randomization
3. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
4. Has received prior radiotherapy within 2 weeks prior to first dose of study intervention
5. Has hypoxia or requires intermittent supplemental oxygen or requires chronic supplemental oxygen
6. Has clinically significant cardiac disease within 12 months from first dose of study intervention
7. Has a history of interstitial lung disease
8. Has symptomatic pleural effusion; a participant who is clinically stable following treatment of this condition is eligible
9. Has preexisting gastrointestinal or non-gastrointestinal fistula
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
11. Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
13. Has an active autoimmune disease that has required systemic treatment in the past 2 years
14. Has a history of noninfectious pneumonitis that required steroids or has current pneumonitis
15. Has an active infection requiring systemic therapy
16. Has a known history of human immunodeficiency virus (HIV) infection
17. Has a known history of Hepatitis B
18. Has radiographic evidence of intratumoral cavitation, encasement or invasion of a major blood vessel
19. Has clinically significant history of bleeding within 3 months prior to randomization
20. Has had an allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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. Overall Survival (OS)

Secondary endpoints 4

1. Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
2. Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
3. Number of Participants Who Experienced At least One Adverse Event (AE)
4. Number of Participants Who Discontinue Study Treatment Due to an AE

Investigational products

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

Test 5

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

Karla Rodriguez-Lopez

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Karla Rodriguez-Lopez

Third parties 9

Locations

14 EU/EEA countries · 66 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 101 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