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).

Study Overview

• Status: Terminated
• Conditions: Recurrent Head and Neck Cancer; Metastatic Head and Neck Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Bempegaldesleukin

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg Bundesland
    • Salzburg, Salzburg Bundesland, Austria, 5020
      • Universitätsklinikum Salzburg, Landeskrankenhaus,
• Greece
  • Attiki
    • Athens, Attiki, Greece
      • Attikon University General Hospital
• Italy
  • Lombardia
    • Brescia, Lombardia, Italy
      • Asst Degli Spedali Civili Di Brescia
• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BEMPEG + Pembrolizumab; Bempegaldesleukin plus pembrolizumab every 3 weeks (q3w) for up to 35 cycles (approximately 2 years).	Drug: Pembrolizumab; Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.; Drug: Bempegaldesleukin; Specified dose on specified days
Active Comparator: Pembrolizumab Monotherapy; Pembrolizumab monotherapy q3w for up to 35 cycles (approximately 2 years).	Drug: Pembrolizumab; Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		Approximately 2 years
Objective Response Rate	To compare the objective response rate (ORR) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy.	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	To compare progression-free survival (PFS) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy.	Approximately 2 years
Time to Deterioration	The time from baseline to a ≥ 10-point decrease with confirmation by the subsequent visit of a ≥ 10-point deterioration from baseline in: • Global health status/quality of life assessment based on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). The EORTC QLQ-C30 is a 30-item questionnaire designed to assess the quality of life of cancer patients. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates a better level of functioning. • Pain and Swallowing based on respective multi-item scales of EORTC QLQ head and neck cancer specific module (EORTC QLQ-H&N35). EORTC QLQ-H&N35 consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates increased severity of symptoms.	Approximately 2 years
Change in Global Health Status/Quality of Life	To compare mean change from baseline in global health status/quality of life scale of EORTC QLQ-C30. The EORTC QLQ-C30 is composed of multi-item scales and single item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), a global health status/HRQoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates a better level of functioning.	Approximately 2 years
Percentage of Patients With Treatment-Emergent Adverse Events and Serious Adverse Events	Compare the overall safety and tolerability based on assessments of treatment-emergent adverse events and serious adverse events	Screening baseline through end of study, approximately 2 years

Collaborators and Investigators

• Sponsor: Nektar Therapeutics
• Collaborators: Merck Sharp & Dohme LLC; SFJ Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2022
• Primary Completion (Actual): April 22, 2022
• Study Completion (Actual): April 22, 2022

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: July 9, 2021
• First Posted (Actual): July 21, 2021

Study Record Updates

• Last Update Posted (Actual): January 12, 2023
• Last Update Submitted That Met QC Criteria: December 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Pembrolizumab; Keytruda; HNSCC; NKTR-214; BEMPEG; Bempegaldesleukin; Head and Neck Squamous-Cell Carcinoma; PROPEL-36
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Recurrence; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: 20-214-36

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No