Real-world Study of First Line Pembrolizumab- or Nivolumab-treated HPV-positive Recurrent/Metastatic Oropharyngeal Squamous Cell Carcinoma

Real-world Study of Patients With Human Papillomavirus-positive Recurrent/ Metastatic Oropharyngeal Squamous Cell Carcinoma Treated With First Line Pembrolizumab or Nivolumab With or Without Chemotherapy

Pembrolizumab and nivolumab (with or without chemotherapy) are used to treat head and neck cancer. The middle part of the throat (oropharynx) is a common location for head and neck cancer. This cancer is known as oropharyngeal squamous cell carcinoma (OPSCC) and is most often caused by human papillomavirus (HPV) infection. This real-world evidence study carried out in the United States (US) will assess patient demographic and clinical characteristics, treatment patterns, and effectiveness of pembrolizumab and nivolumab (with or without chemotherapy) in patients with HPV positive (HPV+) OPSCC after their cancer spread (metastatic) and/or returned (recurrent). The collected real-world data can be compared with data derived from matched study populations in clinical studies that test new therapies in patients with HPV+ OPSCC. This will allow a more reliable evaluation of the clinical benefits and better-informed design of future clinical studies in this patient population.

Study Overview

• Status: Completed
• Conditions: Oropharyngeal Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Pembrolizumab; Drug: Pembrolizumab; Drug: Nivolumab; Drug: Nivolumab

Detailed Description

This non-interventional study will be conducted as a single-phase, multicenter medical chart review of US patients with HPV+ recurrent and/or metastatic (R/M) OPSCC treated with first-line (1L) pembrolizumab or nivolumab (with or without chemotherapy). Participating physicians (Cardinal Health's Oncology Provider Extended Network) and clinical sites (Practice Research Network) will be asked to submit data on patient demographics, clinical characteristics, treatment patterns, and 1L treatment outcomes during a 10-week data collection period. The networks do not overlap, eliminating the chance of duplicate patient records. The completion of data collection defines the study completion date. The data collection period will be followed by a data validation period based on responses of the participating physicians and clinical sites to follow-up questions.

The data obtained in this study will create external control arms (ECAs) comprised of patients with HPV+ R/M OPSCC initiating 1L therapy with pembrolizumab monotherapy, or nivolumab with or without chemotherapy. The use of these ECAs will allow for a more accurate estimation of the effectiveness of therapies currently assessed in interventional clinical studies versus pembrolizumab or nivolumab (with or without chemotherapy) as assessed in this observational study in a non-randomized setting. This information will serve to increase the reliability of the study data from interventional clinical studies investigating therapies in matching indications and patient populations and improve the accuracy of the clinical data to inform future clinical trials.

• Study Type: Observational
• Enrollment (Actual): 662

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Dublin, Ohio, United States, 43017
      • Cardinal Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Real-world patients with HPV+ R/M OPSCC who received 1L pembrolizumab monotherapy, or nivolumab with or without chemotherapy will be evaluated. The ECAs derived from this real-world study are matched to respective study populations from interventional clinical studies. Propensity score matching will be used to generate the ECAs. The baseline characteristics used for matching will encompass key demographic and clinical factors potentially associated with treatment outcomes and may include:

• Type of disease (only recurrent/metastatic including any recurrent)
• Smoking history
• Sex at birth
• Race/Ethnicity
• Hemoglobin

Description

Inclusion Criteria:

• Confirmed diagnosis of HPV+ R/M OPSCC (base and posterior one-third of tongue, the tonsils, soft palate, and lateral pharyngeal walls).
• Initiated and treated with pembrolizumab monotherapy, or nivolumab (monotherapy or in combination with chemotherapy) as 1L therapy for HPV+ R/M OPSCC on or after 05 June 2024 (may have had curative intent treatment including surgery, chemotherapy, and/or radiotherapy for non-metastatic/non-recurrent disease).
• Have access to baseline assessment scan within 30 days prior to initiating 1L therapy for HPV+ R/M OPSCC and response assessment confirmed by objective measurements within 26 weeks of initiation of 1L therapy.
• Must have been followed for 6 months or more since initiation of 1L therapy for R/M OPSCC.

Exclusion Criteria:

• Participation in a controlled clinical trial for 1L R/M OPSCC.
• Central nervous system involvement or other concurrent malignancy at the time of 1L initiation.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ECA 1; A representative sample of real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab monotherapy.	Drug: Pembrolizumab; Given as monotherapy.; Other Names: Keytruda; Drug: Pembrolizumab; Given in combination with chemotherapy.; Other Names: Keytruda; Drug: Pembrolizumab; Given without chemotherapy.
ECA 3; A representative sample of real-world patients with HPV+ R/M OPSCC and high CPS (at least 20 or more) treated with 1L pembrolizumab monotherapy.	Drug: Pembrolizumab; Given as monotherapy.; Other Names: Keytruda; Drug: Pembrolizumab; Given in combination with chemotherapy.; Other Names: Keytruda; Drug: Pembrolizumab; Given without chemotherapy.
ECA 2; A representative sample of real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with chemotherapy.	Drug: Pembrolizumab; Given as monotherapy.; Other Names: Keytruda; Drug: Pembrolizumab; Given in combination with chemotherapy.; Other Names: Keytruda; Drug: Pembrolizumab; Given without chemotherapy.; Drug: Nivolumab; Given in combination with chemotherapy.; Other Names: Opdivo; Drug: Nivolumab; Given without chemotherapy.; Other Names: Opdivo
ECA 4; A representative sample of real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with or without chemotherapy.	Drug: Pembrolizumab; Given as monotherapy.; Other Names: Keytruda; Drug: Pembrolizumab; Given in combination with chemotherapy.; Other Names: Keytruda; Drug: Pembrolizumab; Given without chemotherapy.; Drug: Nivolumab; Given in combination with chemotherapy.; Other Names: Opdivo; Drug: Nivolumab; Given without chemotherapy.; Other Names: Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient demographics with ECA 1	Patient demographics among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab monotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Clinical characteristics with ECA 1	Clinical characteristics among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab monotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Treatment patterns with ECA 1	Treatment patterns among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab monotherapy.	Whole study period (05 June 2024 through 30 April 2025)
1L treatment outcomes with ECA 1	1L treatment outcomes among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab monotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Patient demographics with ECA 2	Patient demographics among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with chemotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Clinical characteristics with ECA 2	Describe the clinical characteristics among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with chemotherapy.	Whole study period (05 June 2024 through 30 April 2025)
1L treatment outcomes with ECA 2	1L treatment outcomes among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with chemotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Treatment patterns with ECA 2	Treatment patterns among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with chemotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Patient demographics with ECA3	Patient demographics among real-world patients with HPV+ R/M OPSCC and with a CPS of at least 20 or more treated with 1L pembrolizumab monotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Clinical characteristics with ECA3	Clinical characteristics among real-world patients with HPV+ R/M OPSCC and with a CPS of at least 20 or more treated with 1L pembrolizumab monotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Treatment patterns with ECA3	Treatment patterns among real-world patients with HPV+ R/M OPSCC and with a CPS of at least 20 or more treated with 1L pembrolizumab monotherapy.	Whole study period (05 June 2024 through 30 April 2025)
1L treatment outcomes with ECA3	1L treatment outcomes among real-world patients with HPV+ R/M OPSCC and with a CPS of at least 20 or more treated with 1L pembrolizumab monotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Patient demographics with ECA 4	Patient demographics among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with or without chemotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Clinical characteristics with ECA 4	Describe the clinical characteristics among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with or without chemotherapy.	Whole study period (05 June 2024 through 30 April 2025)
Treatment patterns with ECA 4	Treatment patterns among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with or without chemotherapy.	Whole study period (05 June 2024 through 30 April 2025)
1L treatment outcomes with ECA 4	1L treatment outcomes among real-world patients with HPV+ R/M OPSCC treated with 1L pembrolizumab or nivolumab with or without chemotherapy.	Whole study period (05 June 2024 through 30 April 2025)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Real-world ECA 1 population versus a population from an interventional clinical study	Compare clinical outcomes of a matched patient population from an interventional clinical study with those of the representative ECA 1 real-world population with HPV+ R/M OPSCC treated with 1L pembrolizumab monotherapy from this study.	Whole study period (05 June 2024 through 30 April 2025)
Real-world ECA 2 population versus a population from an interventional clinical study	Compare clinical outcomes of a matched patient population from an interventional clinical study with those of the representative ECA 2 real-world population with HPV+ R/M OPSCC treated with pembrolizumab or nivolumab with chemotherapy from this study.	Whole study period (05 June 2024 through 30 April 2025)
Real-world ECA 3 population versus a population from an interventional clinical study	Compare clinical outcomes of a matched patient population from an interventional clinical study with those of the representative ECA 3 real-world population with HPV+ R/M OPSCC and with CPS of at least 20 or more treated with pembrolizumab monotherapy from this study.	Whole study period (05 June 2024 through 30 April 2025)
Real-world ECA 4 population versus a population from an interventional clinical study	Compare clinical outcomes of a matched patient population from an interventional clinical study with those of the representative ECA 4 real-world population with HPV+ R/M OPSCC treated with pembrolizumab or nivolumab with or without chemotherapy from this study.	Whole study period (05 June 2024 through 30 April 2025)

Collaborators and Investigators

• Sponsor: Hookipa Biotech GmbH
• Collaborators: Cardinal Health

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2024
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): February 28, 2025

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 8, 2025
• First Posted (Actual): January 13, 2025

Study Record Updates

• Last Update Posted (Estimated): September 9, 2025
• Last Update Submitted That Met QC Criteria: September 8, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; head and neck cancer; HNSCC; nivolumab; pembrolizumab; checkpoint inhibitor; oropharyngeal squamous cell carcinoma; HPV; human papillomavirus; OPSCC; squamous cell cancer; throat; real-world study; PD-L1 therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; pembrolizumab
• Other Study ID Numbers: H-RWE-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No