Principal Investigator: Rachel Lerner, MD
Study Sponsor: Nektar Therapeutics
Location: Frauenshuh Cancer Center
Phase of Study: Phase 1
Purpose of Study:
To test the safety, tolerability, and effectiveness (how well these drugs work together) of NKTR-214 given in combination with pembrolizumab or atezolizumab. We want to find out what effects, good or bad, the study drug has on you and your cancer when combined with pembrolizumab or atezolizumab.
NTKR-214 is a modified (changed in the laboratory) form of a protein called interleukin-2 (or IL-2) which is normally made by your immune system. This protein is designed to trigger (wake up) other cells in your immune system to start attacking your cancer cells. IL-2 has been used for certain cancers for many years so doctors understand many of the risks and benefits.
Pembrolizumab and atezolizumab are prescription medicines used to treat locally advanced or metastatic (has spread into different areas of the body) melanoma, locally advanced or metastatic urothelial bladder cancer or metastatic Stage 4 Non-small cell lung cancer (IV-NSCLC). They are antibodies (known as checkpoint inhibitors) that block a type of protein (PD-1 or PD-L1) that can prevent human immune cells (called T cells) from attacking cancer cells. Pembrolizumab blocks PD-1, and atezolizumab blocks PD-L1.
– Histologically confirmed locally advanced melanoma (pembrolizumab only), locally advanced or metastatic urothelial carcinoma, or metastatic NSCLC.
– Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF).
– Life expectancy > 12 weeks as determined by the Investigator.
– Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
– Measurable disease per RECIST 1.1.
– Patients must not have received prior oncology regimens, including but not limited to inhibitors such as anti PD-1, anti-PD-L1, anti-PD-L2, anti CD137, or anti CTLA-4 (cytotoxic T lymphocyte-associated protein 4) antibody, or any other antibody or drug specifically targeting T cell co stimulation or checkpoint pathways, indoleamine 2,3-dioxygenase pathway inhibitors, cancer vaccines, adoptive cell therapies, or other cytokine therapies.
– MELANOMA patients: must have histologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer (AJCC) staging system
– MELANOMA patients: Ocular melanoma is excluded
– MELANOMA patients: Have not received prior anti-cancer therapy for advanced or metastatic melanoma
– MELANOMA patients: Patients with unknown BRAF mutation status may enroll so long as mutation testing is planned to be performed within 30 days of Cycle 1 Day 1
– NSCLC patients: Histologically confirmed or cytologically confirmed diagnosis of stage IV NSCLC
– NSCLC patients: First-line (pembrolizumab only), patients must have high PD-L1 expression (Tumor Proportion Score [TPS] ≥ 50%) as determined by FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
– NSCLC patients: Second-line (pembrolizumab or atezolizumab), patients must have experienced disease recurrence or progression during or after a prior platinum-based chemotherapy given for advanced or metastatic disease. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations and must not have received chemotherapy.
– If patient is to receive pembrolizumab in combination with NKTR 214, PD L1 expression by TPS should be ≥ 1% as determined by an FDA-approved test.
– UROTHELIAL CARCINOMA patients: Histologically or cytologically documented locally advanced or metastatic urothelial carcinoma
– UROTHELIAL CARCINOMA patients: First-line (pembrolizumab only), patients who are not eligible for cisplatin-containing chemotherapy.
– UROTHELIAL CARCINOMA patients: First-line (atezolizumab only), patients who have disease progression within 12 months of neoadjuvant or adjuvant treatment with chemotherapy.
– UROTHELIAL CARCINOMA patients: Second-line (pembrolizumab or atezolizumab), patients who have disease progression during or following platinum-containing chemotherapy.
– Additional criteria may apply.
– Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug(s).
– Females who are pregnant or breastfeeding.
– Patients who have an active, known or suspected autoimmune disease. Patients requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. (Exceptions include any patient on 10 mg or less of prednisone or equivalent, patients with vitiligo, hypothyroidism stable on hormone replacement, Type I diabetes, Graves’ disease, Hashimoto’s disease, alopecia areata, eczema, or with Medical Monitor approval).
– History of allergy or hypersensitivity to study drug components.
– Active malignancy not related to the current diagnosed malignancy.
– History of organ transplant that requires use of immune suppressive agents.
– Use of warfarin within 14 days of initiating study drug(s). (Note: Low molecular weight heparin is allowed on the study.)
– Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
– Prior surgery or radiotherapy within 14 days of initiating study drug(s). Patients must have recovered from all radiation-related toxicities, not required corticosteroids and have not had radiation pneumonitis.
– Additional criteria may apply