Clinical Trials /

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

NCT04267120

Description:

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.

Related Conditions:
  • Chromophobe Renal Cell Carcinoma
  • Non-Clear Cell Renal Cell Carcinoma
  • Papillary Renal Cell Carcinoma
  • Sarcomatoid Renal Cell Carcinoma
  • Unclassified Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 20-x012
  • NCT ID: NCT04267120

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
LenvatinibLenvima, LenvanixLenvatinib + Pembrolizumab
PembrolizumabKeytruda, MK-3475Lenvatinib + Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
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.
  • Lenvatinib
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  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 or a newly obtained biopsy must be available prior to the first
             dose of study drug for biomarker analysis. In the case archival tissue cannot be
             provided, patients with inaccessible tumors for biopsy specimens can be enrolled
             without a biopsy 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).

        Exclusion Criteria:

          -  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).

          -  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 that required maintenance steroids (>10
             mg of prednisone) or current pneumonitis.

          -  Has received a live-virus vaccination within 30 days of planned treatment start.
             Seasonal flu vaccines that do not contain live virus are permitted.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Through completion of treatment (estimated to be 12 months)
Safety Issue:
Description: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-PD.

Secondary Outcome Measures

Measure:Safety and tolerability of regimen as measured by the number of adverse events
Time Frame:From start of treatment through 120 days after last day of study treatment (estimated to be 16 months)
Safety Issue:
Description:-Will be graded according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Measure:Progression-free survival (PFS)
Time Frame:3 months
Safety Issue:
Description: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).
Measure:Progression-free survival (PFS)
Time Frame:6 months
Safety Issue:
Description: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).
Measure:Progression-free survival (PFS)
Time Frame:12 months
Safety Issue:
Description: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).
Measure:Overall survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:-OS is defined as the time from the date of first dose of study drug until date of death from any cause.
Measure:Overall survival (OS)
Time Frame:6 months
Safety Issue:
Description:-OS is defined as the time from the date of first dose of study drug until date of death from any cause.
Measure:Overall survival (OS)
Time Frame:12 months
Safety Issue:
Description:-OS is defined as the time from the date of first dose of study drug until date of death from any cause.
Measure:Overall survival (OS)
Time Frame:18 months
Safety Issue:
Description:-OS is defined as the time from the date of first dose of study drug until date of death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Washington University School of Medicine

Last Updated

February 10, 2020