NCT05075122

Tolerability and Efficacy of UV1 Vaccine in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Planned for First-line Treatment With Pembrolizumab

Phase 2 Multicenter Study Investigating the Tolerability and Efficacy of UV1 Vaccine in Patients With Recurrent or Metastatic PD-L1 Positive (CPS≥1) Head and Neck Squamous Cell Carcinoma Planned for First-line Treatment With Pembrolizumab

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (estimated)
• Sponsor: Martin-Luther-Universität Halle-Wittenberg · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this study is to determine the clinical performance of UV1 vaccination as add on to standard pembrolizumab treatment in patients with recurrent or metastatic PD-L1 positive (CPS \>=1) head and neck squamous cell carcinoma. Secondary objectives are to determine the efficacy in terms of overall survival ,objective response rate and duration of response. Moreover, this study will explore patient subgroups most likely deriving benefit from a targeted immunotherapy approach combining a checkpoint inhibitor with a cancer vaccine and help to establish liquid biopsy tumor monitoring in HNSCC.

Detailed description

Overall survival of patients with metastatic or recurrent HNSCC has improved over the past decade but remains poor overall. Median overall survival is limited to less than 15 months, with the current standard of care (immune checkpoint blockade with or without chemotherapy). Many patients with HNSCC are frail and therefore cannot tolerate chemotherapy, reducing their treatment options to checkpoint inhibitor. Therefore, the development of effective and tolerable combination regimens is urgently needed, especially in first-line therapy. The FOCUS study will evaluate such a combination regimen in patients with metastatic or recurrent HNSCC. The experimental regimen evaluated in this study will test the first-line standard drug pembrolizumab in combination with the novel UV1 cancer vaccine. In the comparator arm, patients receive pembrolizumab as the standard of care. The aim is to assess whether the addition of UVI can increase the efficacy of the checkpoint inhibitor. Based on currently available data, a decrease in efficacy due to the combination of standard first-line therapy with pembrolizumab is unlikely. The FOCUS study could therefore establish a new 1st-line regimen with increased efficacy and acceptable tolerability, which would need to be compared with the standard of care in a larger phase III trial. Based on the biomarker data from the FOCUS study, a subsequent Phase 3 study would potentially test the regimen only in subpopulations with increased response probability. From the perspective of the individual patient, participants may benefit from the experimental combination through improved efficacy. On the other hand, this is a novel combination study for HNSCC, and there is a risk that efficacy may not improve.

Conditions

• Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	UV1	UV1 vaccination (300 μg) UV1 vaccination will be applied in a dense schedule with three vaccinations during one week before initiation of pembrolizumab, followed by 5 additional vaccinations every 3 weeks on d1 of each cycle (5 cycles in total, duration of treatment will be 13 weeks in total, regular EOT at week 14)
DRUG	Sargramostim for Injection	75 μg GM-CSF as adjuvant per vaccination. Applied in a dense schedule with three injections during one week before initiation of pembrolizumab, followed by 5 additional injections every 3 weeks on d1 of each cycle (5 cycles in total, duration of treatment will be 13 weeks in total, regular EOT at week 14).
DRUG	Pembrolizumab injection	200mg flat dose iv every 3 weeks. Pembrolizumab will be administered beyond the EOT visit at physician discretion until disease progression and up to a maximum of two years (standard of care)

Timeline

• Start date: 2021-08-02
• Primary completion: 2024-08-01
• Completion: 2025-02-01
• First posted: 2021-10-12
• Last updated: 2022-03-09

Locations

10 sites across 1 country: Germany