BEMPEG With Pembrolizumab vs Pembrolizumab Alone in Patients With Metastatic or Recurrent HNSCC (PROPEL-36)

A Phase 2/3, Randomized, Open-label Study to Compare Bempegaldesleukin Combined With Pembrolizumab Versus Pembrolizumab Alone in First-Line Treatment of Patients With Metastatic or Recurrent Head and Neck Squamous-Cell Carcinoma With PD-L1 Expressing Tumors (PROPEL-36)

This is a multicenter, randomized, open-label, Phase 2/3 study that will evaluate the efficacy and safety of bempegaldesleukin (BEMPEG; NKTR-214) combined with pembrolizumab compared with pembrolizumab monotherapy in patients with recurrent or metastatic HNSCC with positive PD-L1 expression (CPS ≥ 1).

Inclusion Criteria:

• Provide written, informed consent to participate in the study and follow the study procedures.

• Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF).

• Have histologically or cytologically-confirmed recurrent or metastatic HNSCC that is considered incurable by local therapies.

  • No prior systemic therapy for recurrent or metastatic disease.
  • The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
  • Patients may not have a primary tumor site of nasopharynx (any histology) and/or unknown primary.

• Have measurable disease based on RECIST 1.1 as determined by the local site Investigator.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Measure Description: GRADE - ECOG PERFORMANCE STATUS

0 - Fully active, able to carry on all pre-disease performance without restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work

2- Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours

• The tumor must have positive PD-L1 expression (i.e., CPS ≥1)

Exclusion Criteria:

• Has disease that is suitable for local therapy administered with curative intent.
• Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
• Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to initiation of study drug
• Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) as determined by the Investigator.
• Has a known additional malignancy that is progressing or has required active treatment within 5 years prior to the first dose of study drug
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy
• Use of an investigational agent or an investigational device within 28 days before the first dose of study drug.
• Prior treatment with an anti PD-1, anti PD-L1, anti-PD-L2, or anti CTLA-4 antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

NOTE: Other protocol defined inclusion/exclusion criteria may apply