A clinical study of different treatments for kidney cancer (MK-3475-03A)

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

10 Dec 2020 → ongoing

Decision date (initial)

2024-01-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506838-68-00

EudraCT number

2019-003609-84

WHO UTN

U1111-1294-4527

ClinicalTrials.gov

NCT04626479

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. Safety Lead-in Phase: To assess the safety and tolerability, and to establish an RP2D if applicable, of treatment combinations that have not been evaluated in a separate study.
2. Efficacy Phase: To assess the safety and tolerability of each treatment arm based on the proportion of participants with AEs.
3. Efficacy Phase: To evaluate objective response (OR) of each treatment arm per RECIST 1.1.

Secondary objectives 4

1. Efficacy Phase: To evaluate the duration of response (DOR) per RECIST1.1.
2. Efficacy Phase: To evaluate progression free survival (PFS) per RECIST1.1.
3. Efficacy Phase: To evaluate overall survival (OS).
4. Efficacy Phase: To evaluate clinical benefit rate (CBR) per RECIST 1.1.

Conditions and MedDRA coding

Renal cell carcinoma

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Has a histologically confirmed diagnosis of locally advanced/metastatic clear cell renal cell carcinoma (ccRCC)
2. Has received no prior systemic therapy for advanced RCC; prior neoadjuvant/adjuvant therapy for RCC is acceptable if completed ≥12 months before randomization/allocation.
3. Is able to swallow oral medication
4. Has adequate organ function
5. Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation
6. Has resolution of toxic effects of the most recent prior therapy to ≤Grade 1
7. Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation
8. Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, vibostolimab/pembrolizumab or a combination of the aforementioned drugs, no contraception is needed
9. Female participants must not be pregnant and not be a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, and vibostolimab/pembrolizumab, for 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention

Exclusion criteria 18

1. Has urine protein ≥1 g/24 hours and has any of the following: (a) a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the first dose of study intervention
2. Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration
3. Has had major surgery within 3 weeks before first dose of study interventions
4. Has a history of lung disease
5. Has a history of inflammatory bowel disease
6. Has preexisting gastrointestinal (GI) or non-GI fistula
7. Has malabsorption due to prior GI surgery or disease
8. Has received prior radiotherapy within 2 weeks of start of study intervention
9. Has received a live or live attenuated vaccine within 30 days before the first dose of study drug; killed vaccines are allowed
10. Has received more than 4 previous systemic anticancer treatment regimens
11. Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
12. Has known additional malignancy that is progressing or has required active treatment within the past 3 years
13. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
14. Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed
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 had an allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. afety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
2. Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs)
3. Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE
4. Efficacy Phase: Number of participants who experience one or more DLTs
5. Efficacy Phase: Number of participants who experience one or more AEs
6. Efficacy Phase: Number of participants who discontinue study treatment due to an AE
7. Efficacy Phase: Objective response rate (ORR)

Secondary endpoints 4

1. Efficacy Phase: Duration of response (DOR)
2. Efficacy Phase: Progression-free survival (PFS)
3. Efficacy Phase: Overall survival (OS)
4. Efficacy Phase: Clinical benefit rate (CBR)

Investigational products

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

Test 7

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

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Manish Sharma

Third parties 4

Locations

5 EU/EEA countries · 12 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

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 33 files

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

Application history

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