Lenvatinib (LEN) in Combination With Pembrolizumab (KEYtruda) in Subjects With Locally Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma (The LENKYN Trial)

NCT04267120 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 202003148
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single-arm, multicenter, phase 2 study of lenvatinib in combination with pembrolizumab (lenvatinib 20 mg/day + pembrolizumab 200mg q3weeks) in subjects with unresectable advanced or metastatic non-clear cell renal carcinoma who have not received any chemotherapy for advanced disease.

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  * ORR is defined as the proportion of subjects who have a best overall response of complete response (CR) or partial response (PR) * CR: Disappearance of target and non-target lesions and normalization of tumor markers. * PR: At least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline sum of diameters. Non target lesions must be non-progressive disease.

  Through completion of treatment (median length 287 days, full range 92-728 days)

Secondary Outcomes (9)

• Safety and Tolerability of Regimen as Measured by Related Adverse Events Experienced by Participant

  From start of treatment through 120 days after last day of study treatment (median length of follow-up 397 days, full range 92-848 days)

• Cumulative Probability of Progression-free Survival (PFS)

  At 3 months

• Cumulative Probability of Progression-free Survival (PFS)

  At 6 months

• Cumulative Probability of Progression-free Survival (PFS)

  At 12 months

• Median Progression-free Survival (PFS)

  Through completion of follow-up (median length 602 days, full range 92-1244 days)

Study Arms (1)

Lenvatinib + Pembrolizumab

EXPERIMENTAL

* Lenvatinib 20 mg/day will be administered orally on a daily basis and pembrolizumab 200 mg will be infused once every 3 weeks. * Subjects may be treated with pembrolizumab for a maximum of 35 cycles or approximately 2 years, but treatment with lenvatinib can continue beyond 2 years if the subject does not meet other treatment discontinuation criteria.

Drug: Lenvatinib; Drug: Pembrolizumab; Procedure: Research blood collection

Interventions

Lenvatinib DRUG

Lenvatinib will be provided by Merck.

Also known as: Lenvima, Lenvanix

Lenvatinib + Pembrolizumab

Pembrolizumab DRUG

Merck will provide pembrolizumab

Also known as: Keytruda, MK-3475

Lenvatinib + Pembrolizumab

Research blood collection PROCEDURE

-Within 2 weeks prior to first dose of study drug, cycle 4 day 1, and at the off-treatment assessment

Lenvatinib + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Locally advanced or metastatic histologically confirmed nccRCC (2, 7). Must have one of the following subtypes of nccRCC:
• papillary RCC
• chromophobe RCC
• TFE-3/B translocation RCC
• SDHB-loss RCC
• TSC1-loss RCC
• sarcomatoid RCC without clear cell component
• unclassified RCC
• Has not received any prior lines of systemic therapy except adjuvant or neoadjuvant treatments.
• Radiologically measurable disease meeting the following criteria:
• At least 1 lesion of ≥ 10 mm in the longest diameter for a non-lymph node or ≥ 15 mm in the short axis diameter for a lymph node which is serially measurable according to iRECIST (Section 12) using computerized tomography (CT) or magnetic resonance imaging (MRI).
• Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of subsequent progressive disease (substantial size increase of ≥20%) to be deemed a target lesion. Patients who received EBRT must be at least 2 weeks out from last RT treatment.
• At least 18 years of age.
• Karnofsky performance status ≥ 70%
• Blood pressure (BP) ≤ 150/90 mmHg at screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to Cycle 1 Day 1.

You may not qualify if:

• Predominant clear cell renal cell carcinoma (RCC)
• Uncontrolled or untreated brain metastasis
• Major surgery performed within 4 weeks prior to the first dose of study drugs or scheduled for major surgery during the study. Subjects must have recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
• Subjects having \>1+ proteinuria on urinalysis will undergo 24-h 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.
• 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.
• Prolongation of QTc interval to \>480 msec.
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
• Active infection (any infection requiring systemic treatment).
• Subject is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
• Serious nonhealing wound, ulcer, or bone fracture.
• Known intolerance to either of the study drugs (or any of the excipients).
• History of organ allograft (subject has had an allogenic tissue/solid organ transplant) or allogeneic stem cell transplant (subject has received blood-forming stem cells from a donor).
• Biologic response modifiers (e.g., granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before first dose of study treatment.
• Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Stanford Cancer Center

Palo Alto, California, 94306, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

lenvatinib; pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Joel Picus, M.D.
• Organization: Washington University School of Medicine

jpicus@wustl.edu

314-362-9115

Study Officials

• Joel Picus, M.D.

  Washington University School of Medicine

  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: SPONSOR

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 12, 2020
• Study Start: July 29, 2020
• Primary Completion: May 9, 2024
• Study Completion: September 1, 2024
• Last Updated: March 21, 2025
• Results First Posted: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months after publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose.

Locations

US (2)