Informations générales (source: ClinicalTrials.gov)
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)
Interventional
Phase 2/Phase 3
BioNTech SE (Voir sur ClinicalTrials)
janvier 2021
avril 2029
05 avril 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 10/04/2025 13:12:10 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Caroline EVEN | 11/06/2024 13:14:17 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| GH PARIS SITE SAINT JOSEPH | Contact (sur clinicalTrials) | ||||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Georges Francois Leclerc - 21079 - Dijon Cedex - France | Contact (sur clinicalTrials) | ||||
| CHU de BORDEAUX, Hopital Saint Andre - 33075 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| CHU de Tours Hopital Bretonneau - 37044 - Tours - France | Contact (sur clinicalTrials) | ||||
| Clinique Victor Hugo - 72000 - Le Mans - France | Contact (sur clinicalTrials) | ||||
| Hopital de la Timone - 13005 - Marseille - France | Contact (sur clinicalTrials) | ||||
| Hopital Prive du Confluent - 44277 - Nantes - France | Contact (sur clinicalTrials) | ||||
| Institut de Radiothérapie Hartmann, GCS CCConcorde - 92300 - Levallois-Perret - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Patients must sign the written pre-screening informed consent form (ICF) before any
pre-screening procedures.
- Patients who present histologically confirmed recurrent or metastatic HPV16+ HNSCC
that is considered incurable by local therapies.
- Patients who have a tumor that expresses PD-L1 [CPS ≥1] as determined by the
European Conformity (CE)-marked/Food and Drug Administration-approved CDx PD-L1
immunohistochemistry 22C3 pharmDx performed according to the manufacturer's
instructions for use.
- Patients must not have had prior systemic anticancer therapy administered in the
incurable recurrent or metastatic setting. Systemic therapy which was completed more
than 180 days prior to randomization, if given as part of multimodal treatment for
locally advanced disease, is allowed.
- Patients who have measurable disease based on RECIST 1.1 as determined by the site
and confirmed by BICR. Tumor lesions situated in a previously irradiated area may be
considered measurable, if progression has been demonstrated in such lesions disease
by RECIST 1.1.
- All patients must provide a tumor tissue sample (formalin fixed paraffin embedded
[FFPE] blocks or both slides and curls) from archival tissue. Alternatively, a fresh
biopsy sample could be provided if a biopsy sample is performed as part of the
patient's standard clinical practice before the first dose of trial treatment. The
sample should be preferably derived from a current site of metastatic or recurrent
disease. Otherwise, a sample from the primary tumor can be submitted.
Key
- Patients must sign the written pre-screening informed consent form (ICF) before any
pre-screening procedures.
- Patients who present histologically confirmed recurrent or metastatic HPV16+ HNSCC
that is considered incurable by local therapies.
- Patients who have a tumor that expresses PD-L1 [CPS ≥1] as determined by the
European Conformity (CE)-marked/Food and Drug Administration-approved CDx PD-L1
immunohistochemistry 22C3 pharmDx performed according to the manufacturer's
instructions for use.
- Patients must not have had prior systemic anticancer therapy administered in the
incurable recurrent or metastatic setting. Systemic therapy which was completed more
than 180 days prior to randomization, if given as part of multimodal treatment for
locally advanced disease, is allowed.
- Patients who have measurable disease based on RECIST 1.1 as determined by the site
and confirmed by BICR. Tumor lesions situated in a previously irradiated area may be
considered measurable, if progression has been demonstrated in such lesions disease
by RECIST 1.1.
- All patients must provide a tumor tissue sample (formalin fixed paraffin embedded
[FFPE] blocks or both slides and curls) from archival tissue. Alternatively, a fresh
biopsy sample could be provided if a biopsy sample is performed as part of the
patient's standard clinical practice before the first dose of trial treatment. The
sample should be preferably derived from a current site of metastatic or recurrent
disease. Otherwise, a sample from the primary tumor can be submitted.
Key
Medical conditions:
- Patients present primary tumor site of nasopharynx (any histology).
- Patients with another primary malignancy that has not been in complete remission for
at least 2 years, with the exception of those with a negligible risk of metastasis
or death (such as adequately treated carcinoma in situ of the cervix, non-invasive
basal or non-invasive squamous cell skin cancer, localized prostate cancer,
non-invasive superficial bladder cancer or breast ductal carcinoma in situ).
Prior/concomitant therapy:
- Patients who have received or currently receive the following therapy/medication:
1. Chronic systemic immunosuppressive treatment including corticosteroid treatment
(prednisone >10 mg daily orally [PO] or intravenously [IV], or equivalent) in
the 7 days prior to the first dose of trial treatment.
2. Prior treatment with other immune-modulating agents that was (a) within fewer
than 4 weeks (28 days) or five half-lives of the agent (whichever is longer)
prior to the first dose of BNT113, or (b) associated with immune-mediated AEs
that have not resolved prior to the first dose of BNT113 or that pose an
additional risk of on-trial complications, per investigator's assessment, or c)
associated with toxicity that resulted in discontinuation of the
immune-modulating agent and that poses an additional risk of on-trial
complications, per investigator's assessment.
3. Prior treatment with live attenuated vaccines within 4 weeks before the first
dose of BNT113.
4. Prior treatment with an investigational drug (including investigational
vaccines) within 4 weeks or five half-lives of the agent (whichever is longer)
before the planned first dose of BNT113.
5. Ongoing treatment with therapeutic PO or IV antibiotics. Note: Patients
receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or chronic obstructive pulmonary disease) may be enrolled.
- Prior treatment with anti-cancer immunomodulating agents, such as blockers of
programmed death receptor-1 (PD-1), PD-L1, tumor necrosis factor receptor
superfamily member 9 (TNRSF9, 4 1BB, CD137), OX 40, therapeutic vaccines, cytokine
treatments, or any investigational agent within 4 weeks or five half-lives of the
agent (whichever is longer) before the first dose of BNT113.
- Treatment with non-systemic anti-cancer therapy (e.g., radiotherapy or surgery)
within 2 weeks prior to randomization. Note: Prior treatment with bone resorptive
therapy, such as bisphosphonates (e.g., pamidronate, zoledronic acid) and denosumab,
is allowed.
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.