Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Camurati-Engelmann Disease

bintrafusp alfa will be administered by intravenous infusion over 60 minutes at a dose of 1200 mg on Day1 and Day15

bintrafusp alfa

Caroline Hoffmann, MD, PhD

Christophe Letrouneau, MD, PhD

This study is a prospective open label, multicenter, phase II, window-of-opportunity preoperative, single-agent trial.

This study aims to evaluate the efficacy, the safety and tolerability profile of bintrafusp alfa in patients with histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, larynx or hypopharynx, previously untreated, with indication of primary surgery. Patients with a diagnosis of head and neck squamous cell carcinoma (HNSCC) from unknown primary will not be enrolled.

The study plans to enrol up to 59 patients in total. Eligible patients who have provided their written informed consent for study participation will be assigned to one the 2 cohorts described below:

Cohort A (43 patients): Non-oropharyngeal HNSCC, or Oropharyngeal squamous cell carcinoma (SCC) that are human papillomavirus (HPV) negative, or Oropharyngeal SCC that are HPV positive and smoker ≥20 pack year (PY).

A Minimax two-stage Simon design will be used with an unacceptable rate of pathological response of 30% or less and a hypothesized actual pathological response rate of 50% or more.

In the first stage, 28 patients will be accrued. If the observed number of patients with a pathological response is 7 or less, then the study for the cohort A will conclude to inefficacy and patient recruitment in this cohort will be stopped.

Cohort B (16 patients): Oropharyngeal SCC that are HPV positive and non-smoker or smoker \<20 PY (former or active).

The design for this cohort will be a single-stage design.

All trial-related interventions will be strictly similar for these 2 cohorts.

Evaluation of Bintrafusp Alfa in Operable and Untreated Head and Neck Squamous Cell Carcinoma

A Phase II Trial Assessing Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in a Pre-operative Setting for Resectable and Untreated Head and Neck Squamous Cell Carcinoma

Individual Participant Data will not be shared at an individual level. Those data will be part of the study database including all enrolled patients.

Pathological tumor response will be evaluated as the percentage of the tumor area showing evidence of anti-tumor activity, such as tumor cell necrosis and/or giant cell/histolytic reaction to keratinous debris

Will be considered as responders, the patients presenting 50% or more, 70% or more, and 90% or more, respectively, of tumor cell death.

The response rate using primary endpoint criteria, by PD-L1 status using Combined Positive Score (CPS) thresholds of 1 and 20. CPS is the number of PD-L1 staining cells (tumor cells and immune cells) divided by the total number of viable tumor cells, multiplied by 100.

The response rate, using primary endpoint criteria, by HPV status determined by p16 staining in cohort A. Two categories will be defined: HPV- and HPV+ (smokers ≥20 PY). HPV+ non-smoker or smoker \<20 PY will be included in cohort B.

Efficacy of bintrafusp alfa by clinical response will be evaluated by measuring changes in tumor size in response to treatment; measured by Magnetic resonance Imaging (MRI) or positron emission tomography (PET) scan and assessed by RECIST v1.1

DFS defined as the delay between the date of the surgery and the occurrence of a loco-regional recurrence and/or a distant metastasis due to the cancer or death whatever the cause for which the patient was included, whichever comes first.

OS defined as the delay between the date of the surgery and the occurrence of death, whatever the cause.

LR-DFS defined as the delay between the date of the surgery and the first occurrence of a loco-regional recurrence due to the cancer or death whatever the cause for which the patient was included.

D-DFS defined as the delay between the date of the surgery and the first occurrence of a distant metastasis due to the cancer or death whatever the cause for which the patient was included.

The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale will assess the severity of sensory neuropathic disorders, this derivative into 5 grades determined by the investigator.

Just before the beginning of the surgery, surgeons will answer a question (4-level: Yes, No, Not evaluable, Unknown) to indicate if their surgical plan would have been different in the absence of ink labelling.

Spots Global Cancer Trial Database for pdl1 blockade