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

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

21 Dec 2020 → ongoing

Decision date (initial)

2024-03-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506839-15-00

EudraCT number

2019-003610-13

WHO UTN

U1111-1294-4557

ClinicalTrials.gov

NCT04626479

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

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 DOR per RECIST 1.1
2. Efficacy Phase: To evaluate PFS per RECIST 1.1
3. Efficacy Phase: To evaluate OS
4. Efficacy Phase: To evaluate 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 10

1. Has a histologically confirmed diagnosis of locally advanced/metastatic clear cell renal cell carcinoma (ccRCC)
2. Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a programmed cell death ligand 1 (PD-(L)1) checkpoint inhibitor (in sequence or in combination with a vascular endothelial growth factor tyrosine kinase inhibitor [VEGF-TKI]) where PD-(L)1 checkpoint inhibitor treatment progression is defined by meeting ALL of the following criteria: (a) has received ≥2 doses of an anti-PD-(L)1 monoclonal antibody (mAb) (b) has shown radiographic disease progression during or after an anti-PD-(L)1 mAb as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by investigator (c) disease progression has been documented within 12 weeks from the last dose of an anti-PD-(L)1 mAb
3. Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a VEGF-TKI (in sequence or in combination with a PD-[L]1 checkpoint inhibitor) where VEGF-TKI treatment progression is defined by meeting the following criterion: has shown radiographic disease progression during or after a treatment with a VEGF-TKI as defined by RECIST 1.1 by investigator
4. Is able to swallow oral medication
5. Has adequate organ function
6. Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation
7. Has resolution of toxic effects of prior therapy to ≤Grade 1
8. Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation
9. 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, MK-4830 or a combination of the aforementioned drugs, no contraception is needed
10. Female participant is not pregnant or breastfeeding and is not 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, MK-4830 or 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 20

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 previously received treatment with a combination of pembrolizumab plus lenvatinib
9. Has received prior treatment with belzutifan
10. Has received prior radiotherapy within 2 weeks of start of study intervention
11. Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention; killed vaccines are allowed
12. Has received more than 4 previous systemic anticancer treatment regimens
13. Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
14. Has known additional malignancy that is progressing or has required active treatment within the past 3 years
15. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
16. 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
17. Has an active infection requiring systemic therapy
18. Has a known history of human immunodeficiency virus (HIV) infection
19. Has a known history of Hepatitis B
20. Has had an allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. Safety 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 experienced 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 (OR)

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

Ding Wang

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Ding Wang

Third parties 4

Locations

5 EU/EEA countries · 13 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 31 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