Atezolizumab and Bevacizumab in Patients With Recurrent or Metastatic Squamous-cell Carcinoma of the Head and Neck

NCT03818061 | Completed Phase 2 DMC

• 1 other identifier: ET 18-156 ATHENA
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 7

Brief Summary

This proof-of-concept study aims to assess the clinical and biological effects of Atezolizumab combined with Bevacizumab in advanced previously treated squamous-cell carcinoma of the head and neck (HNSCC).

Conditions

Head and Neck Neoplasms

Keywords

Atezolizumab; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Overall response rate (ORR), defined as the percentage of patients with a Complete Response (CR) or Partial Response (PR), on two consecutive occasions at least 4 weeks apart, determined by investigator per RECIST v1.

  At 18 weeks

Secondary Outcomes (11)

• Disease control rate

  At 18 weeks

• Best Overall Response Rate

  Every 6 weeks for 2 years then every 9 weeks for 3 years

• Duration of response

  Every 6 weeks for 2 years then every 9 weeks for 3 years

• Progression-free survival

  Every 6 weeks for 2 years then every 9 weeks for 3 years

• Overall survival

  Up to 1 year

Study Arms (2)

HPV +

EXPERIMENTAL

Patient with Human papillomavirus (HPV +) treated by Atezolizumab combined with Bevacizumab.

Drug: Atezolizumab; Drug: Bevacizumab

HPV -

EXPERIMENTAL

Patient without Human papillomavirus (HPV - ) treated by Atezolizumab combined with Bevacizumab.

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

Patients will receive the combination of Atezolizumab 1200 mg and Bevacizumab 15 mg/kg by IV infusion every 3 weeks.

Also known as: Tecentriq

HPV +; HPV -

Bevacizumab DRUG

Patients will receive the combination of Atezolizumab 1200 mg and Bevacizumab 15 mg/kg by IV infusion every 3 weeks.

Also known as: Avastin

HPV +; HPV -

Eligibility Criteria

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

You may qualify if:

• I1. Male or female patient ≥18 years of age at time of informed consent form signature.
• I2. Histologically proven advanced/metastatic HNSCC (oropharynx, oral cavity, hypopharynx and larynx). Patients with cancer of nasopharynx (i.e. cavum cancer) are not eligible.
• I3. Documented radiological progression or relapse after platinum-containing systemic therapy in the advanced/metastatic setting. Patients may have received anti-EGFR agents (in combination or sequential) and other standard first-line treatment for metastatic HNSCC available at time of enrolment.
• I4. Documented tumor HPV status (positive and negative are eligible) based on p16 IHC testing by local testing.
• I5. Measurable disease at baseline according to RECIST V1.1. Note: Lesions intended to be biopsied should not be defined as target lesions. I6. Availability of a representative formalin-fixed paraffin-embedded (FFPE) primary and/or metastatic tumor tissue with an associated pathology report from an archival block.
• I7. Optional : Tumor lesion visible by medical imaging and accessible to repeatable percutaneous or endoscopic sampling that permits core needle biopsy without unacceptable risk of a significant procedural complications, and suitable for retrieval of 4 cores with a needle minimum diameter :16-gauge.
• I8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. I9. Life expectancy \> 18 weeks.
• I10. Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior to C1D1:
• Bone marrow (without transfusion within 2 weeks before C1D1)
• WBC ≥ 2.5 x 109/L
• Hemoglobin ≥ 9.0 g/dL. Patients may be transfused (\> 2 weeks before C1D1) to meet this criterion.
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without granulocyte colony-stimulating factor support within 2 weeks before C1D1.
• Platelets ≥ 100 x 109/L
• Lymphocyte count ≥ 0.5 x 109/L
• Renal function

You may not qualify if:

• E1. Malignancies other than HNSCC within 3 years prior to C1D1 with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localised prostate cancer or ductal carcinoma in situ treated surgically with curative intent).
• E2. More than two prior lines of systemic therapy for recurrent or metastatic HNSCC.
• E3. Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• Note: Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS.
• The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
• Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
• There is no evidence of interim progression between completion of CNS-directed therapy and initiation of study treatment.
• The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, neurosurgical resection within 28 days prior to initiation of study treatment.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted.
• Asymptomatic patients with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.
• E4. Evidence of tumor lesion is hemorrhagic or radiographic evidence of major blood vessel invasion/infiltration of tumor demonstrating \>90° abutment or encasement of a major blood vessel.
• E5. Spinal cord compression not definitively treated with surgery and/or radiation.
• E6. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
• E7. Uncontrolled tumor pain.

Sponsors & Collaborators

• Centre Leon Berard: lead

Study Sites (7)

Centre Léon Bérard

Lyon, 69373, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie

Paris, 75005, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Clinique Mutualiste de l'Estuaire

Saint-Nazaire, 44606, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The sample size calculation will use an adaptive Simon 2-stage design based on the strategy developed by Lin and Shih (Biometrics 2004). This method allows checking the result at the first stage, adjusting the power and success rate if necessary, and adapting the decision rule accordingly. A minimum of 69 patients (up to 110) will be enrolled in 2 parallel independent cohorts depending on the HPV status of their tumors: cohort A (HPV+, N = 42 to 59) and cohort B (HPV-, N = 27 to 51).

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: January 28, 2019
• Study Start: March 26, 2019
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

FR (7)