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Renal Cell CarcinomaPhase 2NCT04267120

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

A Phase 2 study testing Lenvatinib, Pembrolizumab and Research blood collection in people with Renal Cell Carcinoma, run by Washington University School of Medicine at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Cell Carcinoma
What is being tested?
Lenvatinib, Pembrolizumab and Research blood collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
2 sitesUnited States
Study dates
29 Jul 2020to 1 Sep 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.
  • Adequate renal function defined as creatinine <1.5 x ULN or calculated creatinine clearance ≥40 mL/min per the Cockcroft and Gault formula with creatinine levels >1.5 x ULN.
  • Adequate bone marrow function:
  • Absolute neutrophil count (ANC) ≥1500/mm3 (≥1.5 x 103/L)
  • Platelets ≥100,000/mm3 (≥100 x 109/L)
  • Hemoglobin ≥9.0 g/dL
  • Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) ≤1.5
  • Adequate liver function as evidenced by:
  • bilirubin ≤1.5 times the upper limit of normal (ULN)
  • alkaline phosphatase (ALP) ≤3×ULN (in the case of liver metastases ≤5×ULN)
  • alanine aminotransferase (ALT) ≤3×ULN (in the case of liver metastases ≤5×ULN)
  • aspartate aminotransferase (AST) ≤3×ULN (in the case of liver metastases ≤5×ULN).
  • In case ALP is >3×ULN (in the absence of liver metastases) or >5×ULN (in the presence of liver metastases) AND the subject also is known to have bone metastases, the liver specific ALP isoenzyme must be separated from the total and used to assess the liver function instead of the total ALP.
  • Subjects with known brain metastases will be eligible if they have completed the primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection) and if they have remained clinically stable, asymptomatic, and off steroids for at least 2 months before starting study treatment.
  • All females of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [β-hCG]) at the screening visit. Females of childbearing potential* must agree to use a highly effective method of contraception for the entire study period and for 120 days after study discontinuation
  • Male subjects who are partners of women of childbearing potential must follow one of the methods of contraception described in Section 6.5 beginning at least 1 menstrual cycle prior to starting study drugs, throughout the entire study period, and for 120 days after the last dose of study drug, unless the male subjects are totally sexually abstinent or have undergone a successful vasectomy with confirmed azoospermia or unless the female partners have been sterilized surgically or are otherwise proven sterile.
  • Archival tumor tissue from within 3 months (preferred) or up to 6 months (acceptable) must be available prior to the first dose of study drug for biomarker analysis. If no biopsy has been performed in the prior 6 months, a standard of care biopsy is requested if safe and feasible. In the case tissue cannot be provided, patients can be enrolled upon consultation and agreement by the trial PI.
  • Note: In case of submitting unstained cut slides, freshly cut slides should be submitted to the testing laboratory within 14 days from when the slides are cut.
  • -Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • 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.
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  • 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.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. If the required urine pregnancy test is positive (or cannot be confirmed as negative) within 72 hours prior to start of treatment, a serum pregnancy test will be required.
  • Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for 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 36 months.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of up to 10 mg/day of prednisone or equivalent is approved and does not exclude the patient from the trial.
  • Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, > 10 mg of prednisone per day, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. The use of up to 10 mg/day of prednisone or equivalent is approved and does not exclude the patient from the trial.
  • Has a history of (non-infectious) pneumonitis/interstitial lung disease that required maintenance steroids (>10 mg of prednisone) or current pneumonitis/interstitial lung disease.
  • Has received a live-virus vaccination or live-attenuated vaccine within 30 days of planned treatment start. Administration of killed vaccines is allowed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Stanford Cancer Center

    Palo Alto, California, 94306

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Single Arm, Multicenter, Phase 2 Trial to Evaluate the Efficacy of Lenvatinib (LEN) in Combination With Pembrolizumab (KEYtruda) in Subjects With Locally Advanced or Metastatic Non-clear Cell Renal Cell Carcinoma (The LENKYN Trial)

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.

Being tested
Lenvatinib, Pembrolizumab, Research blood collection
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    Also called Lenvima, Lenvanix

    Lenvatinib will be provided by Merck.

  • PembrolizumabDrug

    Also called Keytruda, MK-3475

    Merck will provide pembrolizumab

  • Research blood collectionProcedure or surgery

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

Study groups in NCT04267120
Study groupRoleWhat they receive
Lenvatinib + PembrolizumabExperimental* 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.
Receives: Drug: Lenvatinib; Drug: Pembrolizumab; Procedure: Research blood collection

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

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

    -Will be graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

    Measured: 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)

  2. Cumulative Probability of Progression-free Survival (PFS)

    • PFS is defined as the time from date of first dose of study drug to date of first documentation of disease progression or death, whichever occurs first.
    • Progressive disease: At least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of ≥5 mm. Appearance of new lesions will also constitute PD (including lesions in previously unassessed areas).
    • Cumulative probability is on a scale of 0-1.

    Measured: At 3 months

  3. Cumulative Probability of Progression-free Survival (PFS)

    • PFS is defined as the time from date of first dose of study drug t date of first documentation of disease progression or death, whichever occurs first.
    • Progressive disease: At least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of ≥5 mm. Appearance of new lesions will also constitute PD (including lesions in previously unassessed areas).
    • Cumulative probability is on a scale of 0-1.

    Measured: At 6 months

  4. Cumulative Probability of Progression-free Survival (PFS)

    • PFS is defined as the time from date of first dose of study drug t date of first documentation of disease progression or death, whichever occurs first.
    • Progressive disease: At least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of ≥5 mm. Appearance of new lesions will also constitute PD (including lesions in previously unassessed areas).
    • Cumulative probability is on a scale of 0-1.

    Measured: At 12 months

  5. Median Progression-free Survival (PFS)

    • PFS is defined as the time from date of first dose of study drug to date of first documentation of disease progression or death, whichever occurs first.
    • Progressive disease: At least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of ≥5 mm. Appearance of new lesions will also constitute PD (including lesions in previously unassessed areas).

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

  6. Median Overall Survival (OS)

    -OS is defined as the time from the date of first dose of study drug until date of death from any cause.

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

  7. Cumulative Probability of Overall Survival (OS)

    • OS is defined as the time from the date of first dose of study drug until date of death from any cause.
    • Cumulative probability is on a scale of 0-1.

    Measured: At 6 months

  8. Cumulative Probability of Overall Survival (OS)

    • OS is defined as the time from the date of first dose of study drug until date of death from any cause.
    • Cumulative probability is on a scale of 0-1.

    Measured: At 12 months

  9. Cumulative Probability of Overall Survival (OS)

    • OS is defined as the time from the date of first dose of study drug until date of death from any cause.
    • Cumulative probability is on a scale of 0-1.

    Measured: At 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2020
  2. Study start29 Jul 2020
  3. Primary completion9 May 2024
  4. Study completion1 Sep 2024

Why it stopped: Slow enrollment with low accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04267120
Sponsor's protocol ID
202003148
Status last verified
Mar 2025
First submitted
10 Feb 2020
Last updated
21 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie the results reported in the article after deidentification (text, tables, figures, and appendices).

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib, Pembrolizumab and Research blood collection in people with Renal Cell Carcinoma, run by Washington University School of Medicine at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Through completion of treatment (median length 287 days, full range 92-728 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04267120.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2025.

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