Resumen

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.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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.

Criterios de exclusión

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:
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.
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.
Prior treatment with live attenuated vaccines within 4 weeks before the first dose of BNT113.
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.
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.

Ubicaciones

Centro de Oncología e Investigación Buenos Aires COIBA

Berazategui, Argentina

RECRUITING

Hospital Britanico de Buenos Aires

Ciudad de Buenos Aires, Argentina

WITHDRAWN

Instituto de Oncologia de Cordoba

Córdoba, Argentina

RECRUITING

Centro Oncologico Riojano Integral

La Rioja, Argentina

RECRUITING

Centro de Investigacion Pergamino SA - Clinica Pergamino

Pergamino, Argentina

RECRUITING

Instituto de Oncologia de Rosario

Rosario, Argentina

RECRUITING

Sanatorio Britanico

Rosario, Argentina

RECRUITING

CAIPO Centro para la Atencion Integral del Paciente Oncologico

San Miguel de Tucumán, Argentina

RECRUITING

Clinica Viedma

Viedma, Argentina

WITHDRAWN

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

BNT113

Pembrolizumab

Ubicaciones

Centro de Oncología e Investigación Buenos Aires COIBA

Hospital Britanico de Buenos Aires

Instituto de Oncologia de Cordoba

Centro Oncologico Riojano Integral

Centro de Investigacion Pergamino SA - Clinica Pergamino

Instituto de Oncologia de Rosario

Sanatorio Britanico

CAIPO Centro para la Atencion Integral del Paciente Oncologico

Clinica Viedma

Patrocinadores

Contactos

BioNTech clinical trials patient information