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

NCT04428047 | Terminated Phase 2 DMC

• 2 other identifiers: UC-HNG/19092019-004052-11
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of Head and Neck

Keywords

PDL1 blockade; TGFb trap; PathR; window-of-opportunity preoperative trial

Outcome Measures

Primary Outcomes (1)

• Pathological response (PathR)

  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

  From inclusion to 1 month after surgery

Secondary Outcomes (10)

• Pathological response using a threshold of 50% (PathR50), 70% (PathR70) and 90% (PathR90)

  From inclusion to 1 month after surgery

• Response rate, using primary endpoint criteria, by PD-L1 status

  3 years

• Response rate, using primary endpoint criteria, by HPV status in cohort A

  2 years

• Clinical response

  From inclusion to post-treatment imaging visit, an average of 21 days

• Disease-free survival (DFS)

  12, 18, 24, and 36 months after surgery

Study Arms (1)

bintrafusp alfa

EXPERIMENTAL

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

Drug: bintrafusp alfa

Interventions

bintrafusp alfa DRUG

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

Also known as: M7824

bintrafusp alfa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years
• Patients must have signed a written informed consent form prior to any trial specific procedures
• 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 formalin-fixed paraffin-embedded (FFPE) within no more than 5 working days.
• Absence of distant metastases determined by CT-scan or PET-CT that must be performed within 35 days prior to endoscopy.
• According to the 7th edition American Joint Committee on Cancer (AJCC) eligible stages are as follow:
• T2N1, T2N2, T2N3 T3 or T4 (any N)
• Baseline radiology studies evaluating primary tumor (MRI or CT-scan) must be performed within 28 days prior to endoscopy.
• Patients must have at least 1 lesion superior to 2 cm in larger axis
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Adequate organ and marrow function as defined by the following laboratory results obtained within 28 days prior to the baseline endoscopy:
• Hemoglobin (Hb) ≥9,0 g/dL;
• Absolute neutrophil count (ANC) ≥1,500/mm³;
• Platelet count ≥100,000/mm³;
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 × institutional upper limit of normal (ULN);

You may not qualify if:

• Primary site of head and neck carcinoma in nasopharynx, sinuses, or skin
• Patients receiving other anti-cancer medication such as, chemotherapy, immunotherapy, biologic therapy, targeted therapy, monoclonal antibodies, hormonal therapy (other than leuprolide or other gonadotropin releasing hormone (GnRH) agonists) or other investigational agent within 6 months prior to the first dose of study drug and while on study treatment.
• 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.
• Any previous treatment with a PD-1, PD-L1 agent
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active peptic ulcer disease or gastritis, active bleeding diatheses.
• 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.
• Receipt of live attenuated vaccination within 28 days prior to the first administration of bintrafusp alfa.
• History of (non-infectious) pneumonitis that required steroids within 28 days prior to the first administration of bintrafusp alfa or current pneumonitis.
• Major surgery within 28 days prior to the first administration of bintrafusp alfa and not recovered adequately from the toxicities and/or complications.
• Serious, non-healing or dehiscing, wound, active ulcer, or ongoing bone fracture.
• 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
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of primary immunodeficiency
• History of allogenic organ transplant that requires the use of immunosuppressive drugs
• Pregnant or breast-feeding women

Sponsors & Collaborators

• UNICANCER: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (8)

CHU de Bordeaux

Bordeaux, France

Location

Centre Antoine Lacassagne

Cagnes-sur-Mer, France

Location

Centre Léon Bérard

Lyon, France

Location

CHU La Timone

Marseille, France

Location

Institut Curie

Paris, France

Location

Institut Claudius Régaud

Toulouse, France

Location

Institut de cancérologie de Lorraine

Vandœuvre-lès-Nancy, France

Location

Gustave Roussy Cancer Campus

Villejuif, France

Location

Related Publications (1)

• Saint A, Van Obberghen-Schilling E. The role of the tumor matrix environment in progression of head and neck cancer. Curr Opin Oncol. 2021 May 1;33(3):168-174. doi: 10.1097/CCO.0000000000000730.

  PMID: 33720067 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

bintrafusp alfa protein, human

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Caroline Hoffmann, MD, PhD

  Institut Curie

  PRINCIPAL INVESTIGATOR

• Christophe Letrouneau, MD, PhD

  Institut Curie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: June 11, 2020
• Study Start: February 4, 2021
• Primary Completion: September 4, 2021
• Study Completion: January 7, 2022
• Last Updated: April 6, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)