Study of Efficacy, Safety, and Quality of Life of Pazopanib in Patients With Advanced and/or Metastatic Renal Cell Carcinoma After Prior Checkpoint Inhibitor Treatment

A Prospective International Multicenter Phase II Study to Evaluate the Efficacy, Safety and Quality of Life of Pazopanib in Patients With Advanced and/or Metastatic Renal Cell Carcinoma After Previous Therapy With Checkpoint Inhibitor Treatment

The main purpose of this study was to assess the progression-free survival (PFS) based on local investigator assessment of pazopanib in participants with advanced and/or metastatic renal cell carcinoma (mRCC) following prior treatment with immune checkpoint inhibitors (ICI).

This was a multi-center, open-label, single-arm Phase II study to determine the efficacy, tolerability, safety and quality of life of treatment with pazopanib in subjects with advanced and/or metastatic renal cell carcinoma (RCC) following prior treatment with immune checkpoint inhibitors (ICI).

Subjects could have received prior systemic therapy with an ICI (monotherapy or combination) as 1st or 2nd line RCC treatment. However, they must not have received pazopanib previously. In this study, pazopanib could be administered in the 2nd or 3rd line setting. The therapeutic line for individual subjects was assigned at the time of screening.

Subjects received 800 mg of pazopanib daily until disease progression, unacceptable toxicity, death, pregnancy, start of a new anti-neoplastic therapy, discontinuation at the discretion of the investigator or patient, lost to follow-up or end of study, whichever came first.

Key Inclusion Criteria:

• Histologically confirmed locally recurrent or metastatic predominantly clear cell renal cell carcinoma.
• Measurable disease based on RECIST 1.1 criteria
• Prior systemic therapy with an immune checkpoint inhibitor (monotherapy or combination) as 1st or 2nd line RCC treatment. Note: patients with prior mTOR inhibitor or TKI treatment as monotherapy or in combination with immune checkpoint inhibitor were allowed; however, treatment with immune checkpoint inhibitor (monotherapy or in combination) must have been the last treatment prior to study entry.
• Last dose of immune checkpoint inhibitor therapy received 4 or more weeks before start of study treatment
• Karnofsky performance status ≥70%.
• Potassium, sodium, calcium and magnesium within normal limits of the central laboratory

Key Exclusion Criteria:

• Renal cell carcinoma without any clear (conventional) cell component
• History or evidence of central nervous system (CNS) metastases (patients with pretreated metastases were eligible under certain conditions)
• Prior treatment with pazopanib
• Prior treatment with bevacizumab that was not given in combination with immune checkpoint inhibitor therapy.
• Prior treatment with more than 2 lines of therapy (combination treatments were considered 1 line of therapy)
• Not recovered from toxicity from prior immune checkpoint inhibitor therapy. Recovery was defined as ≤ NCI-CTCAE Grade 1, except for liver function test levels which must be <Grade 1.
• Disease recurrence less than 6 months from the last dose of prior neoadjuvant or adjuvant therapy (including VEGF-R TKI)
• Patients receiving prohibited concomitant medications that could not be discontinued or replaced by safe alternative medication at least 5 half-lives of the concomitant medication or 7 days, whichever was longer, prior to the start of pazopanib treatment.
• Administration of any investigational drug within 4 weeks prior to the first dose of study treatment