Bempegaldesleukin with pembrolizumab in patients with PD-L1 positive Metastatic or Recurrent HNSCC
Research type
Research Study
Full title
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)
IRAS ID
1004011
Contact name
David Chien
Contact email
Sponsor organisation
Nektar Therapeutics
Eudract number
2021-002461-18
Research summary
Research Summary
Head and neck cancer describes a range of tumours that arise in the head and neck including the part of the throat at the back of the mouth behind the oral cavity the gullet (lower part of the throat) and voice box. Head and neck cancer is ranked as the 8th most common cancer in the world.
Current treatment may include combinations of surgery, chemotherapy immunotherapy and radiotherapy and can result in disease control rates ranging between 33% and 86% of patients.
The purpose of this open label study is to evaluate the effectiveness, safety and tolerability of the study drug in patients aged 18 and over with recurrent or metastatic head and neck cancer and positive PD-L1 (a protein that acts as a kind of “brake” to keep the body’s immune responses under control to fight cancer) that is previously untreated.
Participants who meet all eligibility criteria will be randomised in a 1:1 ratio (by chance, like flipping a coin) to receive Bempegaldesleukin plus Pembrolizumab or Pembrolizumab monotherapy. The study drugs are administered via an intravenous (IV) infusion every 3weeks.
The study includes Screening assessments, a 2-year treatment period (up to 35 cycles), a possible second treatment period of 1 year (up to 17 cycles), and Safety Follow ups at 30 and 90 days and Survival Follow Ups every 12 weeks thereafter. The total study duration is up to 5 years.
Assessments include physical examinations, vital signs, ECG, CT Scans, MUGA, Tumour biopsy, blood & urine sample collection for testing and Quality of Life Questionnaires.
Approximately 500 patients will participate worldwide (21 patients from UK hospitals).Summary of Results
This study was carried out by Nektar Therapeutics in order to evaluate the effectiveness, safety and tolerability of the study drug bempegaldesleukinin combination with pembrolizumab compared with pembrolizumab monotherapy in patients aged 18 and over with recurrent or metastatic head and neck Squamous-Cell Carcinoma with PD-L1that is previously untreated.
In terms of efficacy, the results of this study were not met as this study was early terminated as it was reported that their PIVOT-IO-001 study did not meet its primary endpoint of demonstrating an efficacy advantage from addition of bempegaldesleukin to nivolumab therapy in patients with previously untreated inoperable or metastatic melanoma. On 14 April 2022, negative topline results from both PIVOT-09 (renal cell carcinoma) and PIVOT-10 (urothelial cancer) studies were reported. Based on these 3 large negative studies, Nektar Therapeutics and SFJ Pharmaceuticals, Inc. in consultation with the study Independent Data Monitoring Committee (DMC) made the decision to discontinue the PROPEL-36 trial on 21 April 2022. At the time of termination, 1 patient was enrolled and treated in this study.
In conclusion this one patient received 2 cycles of the study drugs (bempegaldesleukin 0.006 mg/kg IV and pembrolizumab 200 mg IV) before the bempegaldesleukin program was discontinued and the study was terminated. The patient experienced a Grade 1 AE (Adverse Event) of cough. No SAEs (Serious Adverse Events) were reported.REC name
South West - Central Bristol Research Ethics Committee
REC reference
21/SW/0160
Date of REC Opinion
24 Dec 2021
REC opinion
Further Information Favourable Opinion