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. MedDRA version: 21.0 Level: LLT Classification code 10041824 Term: Squamous cell carcinoma of esophagus System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Bintrafusp alfa
Product Code: M7824
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: BINTRAFUSP ALFA
CAS Number: 1918149-01
Concentration unit: mg/ml mill
Sponsors
UNICANCER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age =18 years 2.Patients must have signed a written informed consent form prior to any trial specific procedures 3.Histologically or cytologically confirmed HNSCC of the oral cavity, oropharynx, larynx or hypopharynx, previously untreated, with indication of primary surgery. Patients with a diagnosis of HNSCC of occult primary could not be enrolled. In order to avoid repeated biopsies procedures under general anesthesia, patients with clinically highly suspected squamous cell carcinoma could be registered before the histological or cytological proof. In these cases, the diagnosis will be confirmed rapidly after the endoscopy, either by using frozen sections or by reporting the results obtained on FFPE within no more than 5 working days. 4.Absence of distant metastases determined by CT scan or Pet CT that must be performed within 35 days prior to endoscopy. 5.According to the 7th edition AJCC eligible stages are as follow: •T2N1, T2N2, T2N3 •T3 or T4 (any N) 6.Baseline radiology studies evaluating primary tumor (MRI or CT scan) must be performed within 28 days prior to endoscopy. 7.Patients must have at least 1 lesion superior to 2 cm in larger axis 8.ECOG performance status =1 9.Adequate organ and marrow function as defined by the following laboratory results obtained within 28 days prior to the baseline endoscopy: a)Hemoglobin (Hb) =9,0 g/dL; b)Absolute neutrophil count (ANC) =1,500/mm3; c)Platelet count =100,000/mm3; d)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =1.5 × institutional upper limit of normal (ULN); e)Total bilirubin =1.5 × ULN; f)Creatinine clearance >30 mL/min as determined by the Cockcroft-Gault equation (Cockcroft and Gault, 1976) 10.Negative serology for hepatitis B and C 11.Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures 12.Willing and able to provide tumor specimen and blood samples for translational research. 13.Women of childbearing potential must have a negative serum ß-HCG pregnancy test within 7 days prior to the administration of the first study treatment and/or urine pregnancy 48 hours prior to the administration of the first study treatment. 14.Both sexually active women of childbearing potential and males (and their female partners) patients must agree to use two methods of effective contraception, one of them being a barrier method, or to abstain from sexual activity during the study and for at least 2 months after last dose of study drugs. 15.Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial 16.Patients must be affiliated to the social security system or equivalent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
Exclusion criteria: 1.Primary site of head and neck carcinoma in nasopharynx, sinuses, or skin 2.Patients receiving other anti-cancer medication such as, chemotherapy, immunotherapy, biologic therapy, targeted therapy, monoclonal antibodies, hormonal therapy (other than leuprolide or other GnRH agonists) or other investigational agent within 6 months prior to the first dose of study drug and while on study treatment. 3.Patients receiving other anti-cancer non-drug therapies: radiation, or tumor embolization within 6 months prior to the first dose of study drug and while on study treatment. 4.Previous or concurrent cancer within 2 years prior to study inclusion, with the exception of the following cancer types: in situ carcinomas of any location; skin basal cell carcinoma or squamous cell carcinoma stage T1N0M0 or T2N0M0 5.Any previous treatment with a PD-1, PD-L1 agent 6.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, active bleeding diatheses. 7.Current or prior use of immunosuppressive medication within 28 days before the first dose of bintrafusp alfa, with the exceptions of intranasal, intraocular and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid. 8.Receipt of live attenuated vaccination within 30 days prior to the first administration of bintrafusp alfa 9.Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment (within the past 2 years) can be enrolled 10.Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis) 11.History of primary immunodeficiency 12.History of allogenic organ transplant that requires the use of immunosuppressive drugs 13.Pregnant or breast-feeding women 14.Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results 15.Known positive HIV status 16.Participation in another clinical study with an investigational product during the last 30 days. 17.Known hypersensitivity to the study drug, study drug classes, or study drug excipients. 18.Patients under guardianship or deprived of his liberty by a judicial or administrative decision or any condition (e.g., psychiatric illness/social/familial/geographical condition) that would limit compliance with study requirement or compromise the ability of the patients to give written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of bintrafusp alfa, measured by pathological response (PathR), given in a pre-operative setting.;Secondary Objective: 1/To evaluate the efficacy of bintrafusp alfa by alternative outputs: a)The pathological response, using alternative threshold of tumor cell death as compared to the one used for primary objective b)The response rate, using primary endpoint criteria, by PD-L1 status. c)The response rate, using primary endpoint criteria, by HPV status in cohort A. d)The clinical response, as measured by to RECIST v1.1. e)Assessment of disease-free survival (DFS), overall survival (OS), loco-regional disease-free survival (LR-DFS), distant disease-free survival (D-DFS) rates at 12, 18, 24 and 36 months after the surgery. 2/To evaluate the safety and tolerability profile of bintrafusp alfa 3/To evaluate the impact of inking the tumor margins during baseline endoscopy to avoid surgical plan changes putatively induced by tumor shrinking under therapy. EXPLORATORY OBJECTIVE: To evaluate the pharmacodynamics value of potential biomarkers comparing pre and post-treatment blood and tumor samples ;Primary end point(s): Rate of pathological response defined as tumor necrosis and/or giant cell/histolytic reaction to keratinous debris in =10% of tumor area. The measurement of pathological response will be performed under the responsibility of one pathologist per center as soon as the last patient has undergone his surgery (within 1 month). ;Timepoint(s) of evaluation of this end point: 10% of tumor area | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The pathological response, using a threshold of 50% (PathR50), 70% (PathR70) and 90% (PathR90): will be considered as responders, the patients presenting 50% or more, 70% or more and 90% or more of tumor necrosis and/or giant cell/histolytic reaction to keratinous debris. b)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. Pre-treatment tissue specimens will be tested for PD-L1 expression and patients will be categorized as: oCPS <1: No PD-L1 expression oCPS =1: PD-L1 expression. Among this second group, patients will be further classified as =1CPS <20: Low PD-L1 expression and CPS =20: High PD-L1 expression. c)The response rate, using primary endpoint criteria, by HPV status defined 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. d) The clinical response according to RECIST v1.1 on CT or MRI (same imaging than as baseline). e)Assessment of DFS, OS, LR-DFS, and D-DFS rates at 12, 18, 24 and 36 months after the surgery. 2)Evaluation of safety profile of bintrafusp alfa using the common toxicity criteria from the National Cancer Institute - Common terminology criteria for adverse events version 5.0 (NCI-CTCAE v5.0) 3)Evaluation of the impact of inking the tumor margins during baseline endoscopy in avoiding surgical plan changes putatively induced by tumor shrinking under therapy assessed by surgeon questionnaire ;Timepoint(s) of evaluation of this end point: - | — |
Countries
France
Contacts
Public ContactClotilde SIMON
UNICANCER
Outcome results
None listed