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)
Overview
- Phase
- Phase 2
- Intervention
- Lenvatinib
- Conditions
- Renal Cell Carcinoma
- Sponsor
- Washington University School of Medicine
- Enrollment
- 11
- Locations
- 2
- Primary Endpoint
- Overall Response Rate (ORR)
- Status
- Terminated
- Last Updated
- last year
Overview
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.
Investigators
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:
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
Arms & Interventions
Lenvatinib + Pembrolizumab
* 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.
Intervention: Lenvatinib
Lenvatinib + Pembrolizumab
* 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.
Intervention: Pembrolizumab
Lenvatinib + Pembrolizumab
* 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.
Intervention: Research blood collection
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: Through completion of treatment (median length 287 days, full range 92-728 days)
* 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.
Secondary Outcomes
- 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 12 months)
- Median Progression-free Survival (PFS)(Through completion of follow-up (median length 602 days, full range 92-1244 days))
- Median Overall Survival (OS)(Through completion of follow-up (median length 602 days, full range 92-1244 days))
- Cumulative Probability of Overall Survival (OS)(At 18 months)