PROPEL: A Phase 1/2 Trial of NKTR-214 (Cd122-Biased Agonist) Combined with Anti-Pd-1 (pembrolizumab) or Anti-Pd-l1 (atezolizumab) in Patients (pts) with Advanced Solid Tumors.

TPS3115 Background: NKTR-214 is an investigational cytokine designed to target CD122 (IL-2Rβ) expressed on immune cells (CD8+ T cells and NK cells) in order to expand these tumor-killing cells. NKTR-214 monotherapy increases newly proliferative CD8+ T cells and NK cells in tumors and increases cell surface PD-1 and PD-L1 expression, demonstrating a potentially synergistic mechanism with anti-PD-1 therapy. NKTR-214 plus nivolumab resulted in rapid tumor responses in pts with metastatic melanoma (mM), non-small cell lung cancer (mNSCLC), and renal cell carcinoma. Given the early efficacy data and favorable safety profile of NKTR-214 plus nivolumab, PROPEL will evaluate the clinical benefit, safety and tolerability of NKTR-214 combined with pembrolizumab or atezolizumab. Methods: PROPEL (NCT03138889) will enroll approximately 60 pts in 2 separate arms concurrently. The first arm will evaluate NKTR-214 plus pembrolizumab in up to 30 select pts with locally advanced or mM, mNSCLC, or locally advanced or metastatic urothelial bladder cancer (UBC) within the FDA-approved pembrolizumab indications and dosage regimen. The second arm will evaluate NKTR-214 plus atezolizumab in up to 30 select pts with locally advanced or metastatic UBC or mNSCLC within the FDA-approved atezolizumab indications and dosage regimen. NKTR-214 is administered intravenously over 30 (±5) minutes every 3 weeks in an outpatient setting; the first studied dose of NKTR-214 will be 0.006 mg/kg. The primary objectives are to evaluate safety and tolerability and to define the maximum tolerated dose or recommended phase 2 dose of NKTR-214 combined with pembrolizumab or atezolizumab. The secondary objectives are to evaluate preliminary anti-tumor activity and efficacy by assessing overall survival and progression-free survival. In addition, the study will assess the immunological effects of treatment and the association between efficacy measures and PD-L1 expression in tumors. Treatment may continue beyond progression if there is clinical benefit as determined by the investigator. Enrollment is ongoing in the U.S. Clinical trial information: NCT03138889.