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

Study Overview
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Brief Summary
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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).

Official Title
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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)

Conditions
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Metastatic Head and Neck Cancer, Recurrent Head and Neck Cancer

Intervention / Treatment
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* Drug: Bempegaldesleukin
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PROPEL-36, Head and Neck Cancer, Head and Neck Squamous-Cell Carcinoma, HNSCC, BEMPEG, Bempegaldesleukin, NKTR-214, Keytruda, Pembrolizumab