Phase II Trial of Pembrolizumab in Recurrent or Metastatic HNSCC (POPPY)

A Phase II Trial to Assess the Efficacy and Safety Profile of Pembrolizumab in Patients With Performance Status 2 With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

A single-arm phase II trial to assess the efficacy and safety profile of pembrolizumab in patients with performance status of 2 with recurrent or metastatic squamous cell carcinoma of the head and neck. Patients will receive best supportive care + pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months

Study Overview

• Status: Recruiting
• Conditions: Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Emily Ambrose; Phone Number: 020 7679 9483; Email: ctc.poppy@ucl.ac.uk
• Study Contact Backup: Name: Rubina Begum; Phone Number: 020 7679 9514; Email: ctc.poppy@ucl.ac.uk

Study Locations

• United Kingdom
  • Aberdeen, United Kingdom
    • Recruiting
    • Aberdeen Royal Infirmary (NHS Grampian)
  • Bristol, United Kingdom
    • Recruiting
    • Bristol Haematology and Oncology Centre (University Hospital Bristol NHS Foundation Trust)
  • Edinburgh, United Kingdom
    • Recruiting
    • Western General Hospital (NHS Lothian)
  • Ipswich, United Kingdom
    • Recruiting
    • East Suffolk and North Essex NHS Foundation Trust
  • London, United Kingdom
    • Recruiting
    • University College London Hospital
  • London, United Kingdom
    • Recruiting
    • Guy's and St Thomas' NHS Foundation Trust
  • Manchester, United Kingdom
    • Recruiting
    • The Christie NHS Foundation Trust
  • Northwood, United Kingdom
    • Recruiting
    • East and North Hertfordshire NHS Trust
  • Romford, United Kingdom
    • Recruiting
    • Queens Hospital (Barking, Havering and Redbridge University Hospitals NHS Trust)
  • Taunton, United Kingdom
    • Recruiting
    • Musgrove Park Hospital (Somerset NHS Foundation Trust)
  • Truro, United Kingdom
    • Recruiting
    • Royal Cornwall Hospital Trust
  • Wirral, United Kingdom
    • Recruiting
    • The Clatterbridge Cancer Centre NHS Foundation Trust

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Histologically confirmed recurrent or metastatic squamous cell carcinoma of the head and neck that is considered incurable by local therapies.
2. Measurable disease evaluated by RECIST v1.1
3. WHO performance status of 2
4. Life expectancy of at least 12 weeks
5. Aged ≥ 18 years of age

6. Adequate Bone marrow function:

   • Absolute neutrophils grade 0 or 1 (using CTCAE v5)
   • Platelets grade 0 or 1
   • Haemoglobin grade 0 or 1

7. Adequate renal function:

   Creatinine grade 0 or 1 Calculated glomerular filtration rate (GFR) ≥ 50 mL/min estimated using validated creatinine clearance calculation (e.g. Cockcroft-Gault or Wright formula). If calculated GFR is < 50 mL/min then an isotope GFR assessment (Cr51-EDTA or 99mTc-DTPA) should be performed. If an isotope GFR test is unavailable an estimation from 24 hour urine collection may be used

8. Adequate liver function:

   Serum bilirubin grade 0 or 1 AST and ALT grade 0 or 1 (up to grade 2 for patients with liver metastases)

9. Willing to use contraception for the duration of trial treatment and for 120 days after completion of treatment
10. Willing to have a new biopsy, if site of disease is accessible and considered safe to biopsy by investigator If newly obtained samples cannot be obtained (e.g. inaccessible disease or patient safety concern) sites may submit archival tissue only upon agreement from the sponsor
11. Able to give informed consent, indicating that the patient has been informed of and understands the experimental nature of the study, possible risks and benefits, trial procedures, and alternative options
12. Willing and able to comply with the protocol for the duration of the study, including the treatment plan, investigations required and follow up visits

Exclusion Criteria:

1. Patients with undifferentiated nasopharyngeal or sino-nasal cancers
2. Disease suitable for treatment with curative intent
3. Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent
4. Any investigational agents within 4 weeks prior to registration
5. Anti-cancer monoclonal antibody therapy within 4 weeks prior to registration
6. Chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to registration
7. Patients with concurrent or previous malignancy that could compromise assessment of the primary or secondary endpoints of the trial
8. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
9. Grade 3 or 4 peripheral neuropathy
10. Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinician's judgment, could interfere with patient safety or obtaining informed consent

11. Active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they:

    Are stable, without evidence of progression for at least four weeks prior to the first dose of trial treatment Have no evidence of new or enlarging brain metastases Have no evidence of leptomeningeal disease Are not using steroids for at least 7 days prior to trial treatment

12. Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is detected) NB: Without known history, testing is required to determine eligibility. Hepatitis C antibody testing is allowed for screening purposes in sites where HCV RNA is not part of standard of care
13. Immunocompromised patients (e.g. known HIV positive status)*
14. Prior organ transplantation including allogenic stem-cell transplantation
15. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids, or current pneumonitis/interstitial lung disease
16. Active infection requiring systemic therapy
17. Has received a live vaccine within 30 days prior to registration (seasonal flu vaccines that do not contain live virus are permitted)
18. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (NB: the use of physiologic doses of corticosteroids may be approved after consultation with UCL CTC)

19. Active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with the following are eligible:

    Autoimmune-related hyperthyroidism or autoimmune-related hypothyroidism who are in remission or on a stable dose of thyroid-replacement hormone Vitiligo Psoriasis

20. Current use of immunosuppressive medication, except for the following:

intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisolone or equivalent (after approval by UCL CTC) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)

*Testing for HIV for the POPPY trial is not mandatory, however if this test has been done the result should be known prior to registration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pembrolizumab + best supportive care; Best supportive care and pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months	Drug: Pembrolizumab; Patients will receive best supportive care + pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate at 24 weeks assessed using iRECIST	Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST	24 weeks after registration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate assessed using iRECIST	Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST	12 months after registration
Best Response Rate- measured using the change from baseline tumour size. Assessed using iRECIST.	Best Response Rate, defined as proportion of patients who have a CR or PR as their best response, measured using the change from baseline tumour size, assessed using iRECIST	6 months after registration
Clinical Benefit Rate -defined as patient's best response rate lasting at least 18 weeks	Clinical Benefit Rate, defined as proportion patients who have achieved CR, PR or SD as their best response lasting at least 18 weeks	From start of treatment to 30 months post start of treatment
Duration of Response- defined as the time from first documented evidence of CR or PR until disease progression or death.	Duration of Response, defined as the time from first documented evidence of CR or PR until disease progression or death	From start of treatment to 30 months post start of treatment
Time to Progression -defined as time from registration to the first documented disease progression	Time to Progression, defined as time from registration to the first documented disease progression	From registration to 30 months post start of treatment
Progression Free Survival defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first.	Progression Free Survival, defined as the time from registration to the first documented disease progression or death due to any cause, whichever occurs first.	From registration to 30 months post start of treatment
Overall Survival- defined as the time from registration to death due to any cause.	Overall Survival, defined as the time from registration to death due to any cause.	From registration to 30 months post start of treatment
Frequency and severity of adverse events- throughout the patient's treatment and until 6 months after completion of trial treatment.	Frequency and severity of adverse events	From date of registration until 6 months after completion of trial treatment

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Martin Forster, FRCP PhD, University College, London

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2019
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): January 31, 2026

Study Registration Dates

• First Submitted: January 15, 2019
• First Submitted That Met QC Criteria: January 22, 2019
• First Posted (Actual): January 23, 2019

Study Record Updates

• Last Update Posted (Actual): June 9, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Head and Neck Cancer; Pembrolizumab; Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head and Neck Squamous Cell Carcinoma
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Disease Attributes; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Recurrence; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: UCL/17/0396

Drug and device information, study documents

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