An Open-label Phase II/III Randomized Trial of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Monotherapy as a First Line Therapy in Patients With Unresectable Recurrent, or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Which is Positive for Human Papilloma Virus 16 (HPV16+) and Expresses PD-L1 (AHEAD-MERIT)

NCT04534205 Phase 2/Phase 3 RECRUITING

An open-label, controlled, multi-site, interventional, 2-arm, Phase II/III trial of BNT113 in combination with pembrolizumab vs pembrolizumab monotherapy as first line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing programmed cell death ligand-1 (PD-L1) with combined positive score (CPS) ≥1. This trial has two parts. Part A, is an initial non-randomized Safety Run-In Phase to confirm the safety and tolerability at the selected dose range level of BNT113 in combination with pembrolizumab. Part B, is a randomized part to generate pivotal efficacy and safety data of BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy in the first line setting in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing PD-L1 with CPS ≥1. Patients included in the Safety Run-In Phase of the trial (Part A) will not be randomized to Part B and will continue on-trial treatment (BNT113 plus pembrolizumab) within Part A. For Part B, an optional pre-screening phase is available for all patients where patients' tumor samples may be submitted for central HPV16 DNA and central PD-L1 expression testing prior to screening into the main trial. Patients will be treated with BNT113 in combination with pembrolizumab or with pembrolizumab monotherapy for approximately up to 24 months.

Details

Lead sponsor	BioNTech SE
Phase	Phase 2/Phase 3
Status	RECRUITING
Enrolment	350
Start date	2021-01-07
Completion	2029-04

Conditions

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

Interventions

• BNT113
• Pembrolizumab

Primary outcomes

• Part A - Occurrence of treatment-emergent adverse event (TEAE) - BNT113 in combination with pembrolizumab — up to 27 months
  TEAE assessed according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) including Grade ≥3, serious, and fatal TEAEs, by relationship.
• Part B - Overall survival (OS) — up to 48 months
  OS defined as the time from randomization to death from any cause.
• Part B - Progression-free survival (PFS) — up to 48 months
  PFS defined as the time from randomization to the first objective tumor progression (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\] assessed by the blinded independent central review \[BICR\]), or death from any cause, whichever occurs first.

Countries

United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, France, Germany, Hungary, Israel, Italy, Mexico, Poland, Portugal, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom