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

• ClinicalTrials.gov Identifier: NCT03813836
• Recruitment Status: Recruiting
• First Posted: January 23, 2019
• Last Update Posted: June 2, 2022
• Sponsor: University College, London
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): University College, London

Tracking Information

• First Submitted Date: January 15, 2019
• First Posted Date: January 23, 2019
• Last Update Posted Date: June 2, 2022
• Actual Study Start Date: July 5, 2019
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 30, 2022)

Disease control rate at 24 weeks assessed using iRECIST [ Time Frame: 24 weeks after registration ]

Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST

Original Primary Outcome Measures (submitted: January 22, 2019)

Disease control rate at 24 weeks [ Time Frame: 24 weeks after registration ]

Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST

Current Secondary Outcome Measures (submitted: May 30, 2022)

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

Original Secondary Outcome Measures (submitted: January 22, 2019)

• Disease Control Rate at 12 months [ Time Frame: 12 months after registration ]
  Disease control rate (proportion of patients with CR, PR or SD) assessed using iRECIST
• Best Response Rate [ Time Frame: 6 months after registration ]
  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 modified RECIST
• Clinical Benefit Rate [ Time Frame: From start of treatment to 30 months post start of treatment ]
  Clinical Benefit Rate, defined as proportion patients who have achieved CR, PR or SD as their best response lasting at least 18 weeks
• Duration of Response [ Time Frame: 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
• Time to Progression [ Time Frame: From registration to 30 months post start of treatment ]
  Time to Progression, defined as time from registration to the first documented disease progression
• Progression Free Survival [ Time Frame: 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.
• Overall Survival [ Time Frame: From registration to 30 months post start of treatment ]
  Overall Survival, defined as the time from registration to death due to any cause.
• Frequency and severity of adverse events [ Time Frame: From date of registration until 6 months after completion of trial treatment ]
  Frequency and severity of adverse events

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase II Trial of Pembrolizumab in Recurrent or Metastatic HNSCC
• Official Title: 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
• Brief Summary: 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Metastatic Head and Neck Squamous Cell Carcinoma
• Recurrent Head and Neck Squamous Cell Carcinoma

Intervention

Drug: Pembrolizumab

Patients will receive best supportive care + pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months

Other Name: Keytruda

Study Arms

Experimental: pembrolizumab + best supportive care

Best supportive care and pembrolizumab 200mg every 3 weeks for a maximum duration of 24 months

Intervention: Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 22, 2019): 65
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 31, 2026
• Estimated Primary Completion Date: July 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Emily Ambrose; 020 7679 9483; ctc.poppy@ucl.ac.uk

Contact: Sharon Forsyth; 020 7679 9264; ctc.poppy@ucl.ac.uk

• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03813836
• Other Study ID Numbers: UCL/17/0396
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University College, London
• Original Responsible Party: Same as current
• Current Study Sponsor: University College, London
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Martin Forster, FRCP PhD; University College, London

• PRS Account: University College, London
• Verification Date: May 2022