Pembrolizumab + Lenvatinib for First Line Non-Clear Cell, Renal Cell Carcinoma

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 Feb 2021 → 21 Oct 2025

Decision date (initial)

2023-09-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC · Eisai Limited

External identifiers

EU CT number

2023-504944-32-00

EudraCT number

2020-004087-26

WHO UTN

U1111-1290-4553

ClinicalTrials.gov

NCT04704219

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Safety

To evaluate the objective response rate (ORR) of pembrolizumab + lenvatinib per response evaluation criteria in solid tumors 1.1 (RECIST 1.1) by blinded independent central review (BICR)

Secondary objectives 6

1. To evaluate the duration of response (DOR) of pembrolizumab + lenvatinib in participants with a confirmed complete response (CR) or partial response (PR) per RECIST 1.1 by BICR
2. To evaluate progression-free survival (PFS) per RECIST 1.1 by BICR in participants receiving pembrolizumab + lenvatinib
3. To evaluate the overall survival (OS) of participants receiving pembrolizumab + lenvatinib
4. To evaluate the clinical benefit ratio (CBR) of pembrolizumab + lenvatinib per RECIST 1.1 by BICR
5. To evaluate the disease control rate (DCR) of pembrolizumab + lenvatinib per RECIST 1.1 by BICR
6. To evaluate the safety of pembrolizumab + lenvatinib

Conditions and MedDRA coding

Non-clear Cell Renal Cell Carcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Must have a histologically confirmed diagnosis of nccRCC.
2. Has locally advanced/metastatic disease (ie, Stage IV per the American Joint Committee on Cancer).
3. Has received no prior systemic therapy for advanced nccRCC. Note: Prior neoadjuvant/adjuvant therapy for nccRCC is acceptable if completed >12 months prior to allocation.
4. Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of study medication or refrain from heterosexual intercourse during this period.
5. Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last.
6. Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
7. Has submitted an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
8. Has Karnofsky Performance Status (KPS) ≥70% as assessed within 10 days prior to the start of study intervention.
9. Has adequately controlled blood pressure with or without antihypertensive medications.
10. Have adequate organ function.

Exclusion criteria 24

1. Has collecting duct histology.
2. A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study intervention.
3. Has a left ventricular ejection fraction below the institutional (or local laboratory) normal range.
4. Has radiographic encasement or invasion of a major blood vessel, or of intratumoral cavitation.
5. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.
6. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
7. Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
8. Has had major surgery within 3 weeks prior to first dose of study intervention.
9. Has received prior therapy with an anti-programmed cell-death 1 (PD-1), anti-programmed cell-death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
10. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to allocation.
11. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
12. Has received a live or attenuated vaccine within 30 days before the first dose of study intervention.
13. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
15. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
16. Has known active CNS metastases and/or carcinomatous meningitis.
17. Has severe hypersensitivity (≥Grade 3) to pembrolizumab, lenvatinib and/or any of their excipients.
18. Has an active autoimmune disease that has required systemic treatment in past 2 years.
19. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
20. Has an active infection requiring systemic therapy.
21. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
22. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus.
23. Has a known history of active tuberculosis (TB; Bacillus tuberculosis).
24. Has had an allogenic tissue/solid organ transplant.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) is defined as the percentage of participants with a complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Secondary endpoints 7

1. Duration of Response (DOR) is defined for participants who demonstrate confirmed CR or PR as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
2. Progression-free Survival (PFS) is defined as the time from the date of first dose to the first documented progressive disease (PD) per RECIST 1.1 by BICR or death from any cause, whichever occurs first.
3. Overall Survival (OS) is defined as the time from date of first dose until death from any cause.
4. Clinical Benefit Ratio (CBR) is defined as the percentage of participants who achieved CR, PR, or stable disease (SD) for at least 6 months per RECIST 1.1 by BICR.
5. Disease Control Rate (DCR) is defined as the percentage of participants who achieved CR, PR, or SD per RECIST 1.1 by BICR.
6. Number of Participants Who Experienced One or More Adverse Events (AEs).
7. Number of Participants Who Discontinued Study Medication Due to an AE.

Investigational products

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

Test 3

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 5

Locations

5 EU/EEA countries · 16 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 40 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