Perioperative Lenvatinib With Pembrolizumab in Patients With Locally Advanced Nonmetastatic Clear Cell Renal Cell Carcinoma

NCT04393350 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 4 other identifiers: STUDY00000009NCI-2020-01064Winship4955-20P30CA138292
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well lenvatinib and pembrolizumab before surgery work in treating patients with kidney cancer that has spread from its original site of growth to nearby tissues or lymph nodes but has not spread to other places in the body (non-metastatic). Lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving lenvatinib and pembrolizumab before surgery may kill more tumor cells.

Conditions

Kidney Cancer; Stage IV Renal Cell Cancer AJCC v8; Stage III Renal Cell Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (Complete and Partial Responses)

  Will assess the proportion of patients with a reduction in overall tumor burden from baseline after 12 weeks of treatment with neoadjuvant lenvatinib and pembrolizumab.

  Baseline until end of Cycle 1 (4 Cycles (12 weeks)

Secondary Outcomes (3)

• Incidence of Adverse Events (AEs)

  From treatment phase up to 14 day post treatment

• Overall Survival (OS)

  1 and 3 years

• Disease Free Survival (DFS)

  1 & 3 years

Other Outcomes (4)

• Biomarker Analysis

  Up to 4 years after study start

• Quality of Life: Functional Assessment of Cancer Therapy-Kidney Specific Index-19 Questionnaire

  Up to 4 years after study start

• Fried Frailty Score

  Up to 4 years after study start

Study Arms (1)

Treatment (lenvatinib, pembrolizumab)

EXPERIMENTAL

Patients receive lenvatinib PO QD on days 1-21 and pembrolizumab IV over 30 minutes on day 1. Treatments repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Lenvatinib; Drug: Lenvatinib Mesylate; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Lenvatinib DRUG

Given PO

Also known as: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

Treatment (lenvatinib, pembrolizumab)

Lenvatinib Mesylate DRUG

Given PO

Also known as: 4-[3-Chloro-4-(N''-cyclopropylureido)phenoxy]7-methoxyquinoline-6-carboxamide Mesylate, E7080, Lenvima, Multi-Kinase Inhibitor E7080

Treatment (lenvatinib, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (lenvatinib, pembrolizumab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (lenvatinib, pembrolizumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (lenvatinib, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a renal mass consistent with a clinical stage \>= T3Nx or TanyN+ or deemed unresectable by surgeon
• Renal cell carcinoma with clear cell component on pre-treatment biopsy of the primary tumor
• The participant (or legally acceptable representative if applicable) provides written informed consent and the willingness and ability to comply with all aspects of the protocol
• Have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Absolute neutrophil count (ANC) \>= 1500/uL (specimens must be collected within 72 hours prior to the start of study treatment)
• Platelets \>= 100 000/uL (specimens must be collected within 72 hours prior to the start of study treatment)
• Hemoglobin \>= 9.0 g/dL (specimens must be collected within 72 hours prior to the start of study treatment) or ≥5.6 mmol/La
• Renal:
• Creatinine =≤1.5 × ULN OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl)=≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN.
• Hepatic:
• Total bilirubin=≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels \>1.5 × ULN AST (SGOT) and ALT (SGPT)=≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
• Coagulation:
• International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT)=≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
• ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
• Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.

You may not qualify if:

• Evidence of metastatic disease on pre-treatment imaging
• The subject has received of any type of cytotoxic, biologic or other systemic anticancer therapy for kidney cancer
• The subject has received any other type of investigational agent within 28 days before the first dose of study treatment
• Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for localized prostate cancer, definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within the past 24 months
• Prior treatment with lenvatinib or any agent directed against PD-1, PD-L1 or PD-L2, or another stimulatory or co inhibitory T-cell receptor (e.g. CTLA-4, OX 40, CD137)
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
• Subjects having \> 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein \>= 1 g/24-hour will be ineligible
• Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment
• Prolongation of corrected QT (QTc) interval to \> 480 msec per electrocardiogram (ECG) within 28 days before first dose of study treatment
• Clinically significant hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g. pulmonary hemorrhage) within 3 weeks prior to the first dose of study drug
• Serious non-healing wound/ulcer/bone fracture

Sponsors & Collaborators

• Emory University: lead
• Merck Sharp & Dohme LLC: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Dr. Mehmet Asim Bilen
• Organization: Emory University

mehmet.a.bilen@emory.edu

4047781900

Study Officials

• Mehmet A Bilen, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 14, 2020
• First Posted: May 19, 2020
• Study Start: June 22, 2020
• Primary Completion: September 13, 2024
• Study Completion (Estimated): December 11, 2026
• Last Updated: April 20, 2026
• Results First Posted: April 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)