Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Participants With Selected Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: lenvatinib; pembrolizumab
Intervention description: lenvatinib capsules; pembrolizumab intravenous infusion
Intervention MeSH terms: Pembrolizumab; Lenvatinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: solid tumors; non-small cell lung cancer; predominantly clear cell renal cell carcinoma; endometrial carcinoma; urothelial carcinoma; squamous cell carcinoma of the head and neck; non-uveal melanoma; E7080; lenvatinib; pembrolizumab; Japan

Summary:

      This is an open-label Phase 1b study designed to confirm the tolerability and safety of
      lenvatinib in combination with pembrolizumab in participants with selected solid tumors
      (non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial
      carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma
      [excluding uveal melanoma]).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically and/or cytologically confirmed selected solid tumor types that have
             progressed after treatment with standard therapies or for which there are no other
             appropriate therapies available.

        The selected tumor types are: non-small cell lung cancer, predominantly clear cell renal
        cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the
        head and neck, or melanoma (excluding uveal melanoma)

          -  At least 1 measurable target lesion according to modified Response Evaluation Criteria
             In Solid Tumors (RECIST) 1.1

          -  Participants must have an Eastern Cooperative Oncology Group (ECOG)-Performance Status
             (PS) of 0 to 1.

          -  Adequate liver function as evidenced by bilirubin ≤1.5×ULN and alkaline phosphatase
             (ALP), alanine aminotransferase (ALT), and 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 participant also
             is known to have bone metastases, the liver-specific ALP must be separated from the
             total and used to assess the liver function instead of the total ALP.

          -  Males or females age ≥20 years at the time of informed consent

          -  Life expectancy of 12 weeks or more

          -  Voluntary agreement to provide written informed consent and the willingness and
             ability to comply with all aspects of the protocol

        Exclusion Criteria:

          -  Prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is
             shorter) or any investigational agent within 28 days prior to the first dose of study
             drugs. All toxicities related to prior treatments must be resolved to Grade ≤1 (except
             alopecia).

          -  Prior treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent,
             excluding cancer types such as melanoma and non-small cell lung cancer where prior
             treatment with one anti-PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed

          -  Participants must have recovered adequately from any complications from major surgery
             prior to starting therapy.

          -  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 (Fridericia formula) interval to >480 milliseconds (ms)

          -  Active infection (any infection requiring systemic treatment)

          -  Participant is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis
             B, or Hepatitis C

          -  Known intolerance to either of the study drugs (or any of the excipients)

          -  History of organ allograft

          -  Any medical or other condition which, in the opinion of the investigator, would
             preclude participation in a clinical trial

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis, or has a history of interstitial lung disease

          -  Females who are breastfeeding or pregnant at Screening or Baseline.

          -  Females of childbearing potential.

          -  Participants must be on a stable dose of the same oral hormonal contraceptive product
             for at least 4 weeks before dosing with study drug and for the duration of the study.