Study of IPH2201 (Monalizumab) and Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02643550
Recruitment Status : Recruiting
First Posted : December 31, 2015
Last Update Posted : April 23, 2018
Information provided by (Responsible Party):
Innate Pharma

Brief Summary:
The objective of this study is to evaluate in a 3 +3 design, the safety of escalating doses of IPH2201 given IV in combination with cetuximab in patients who have received prior systemic regimen(s) for recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). A cohort expansion will evaluate antitumor activity of the combination.

Condition or disease Intervention/treatment Phase
Head and Neck Neoplasms Biological: IPH2201 Biological: CETUXIMAB Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b/2 Trial of IPH2201 And Cetuximab in Patients With Human Papillomavirus (HPV) (+) and HPV (-) Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Study Start Date : December 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Dose escalation of IPH2201 (MONALIZUMAB) + CETUXIMAB
Biological: IPH2201
Five dose levels of Monalizumab will be tested in the dose escalation part: 0.4, 1, 2, 4 and 10 mg/kg every 2 weeks.The patients will then receive the recommended dose for phase 2.

Biological: CETUXIMAB
The first dose of Cetuximab will be 400 mg/m2 IV.All subsequent doses will be 250 mg/m2

Primary Outcome Measures :
  1. Occurrence of Dose Limiting Toxicities (DLT) [ Time Frame: within 4 weeks after first administration ]

Secondary Outcome Measures :
  1. Objective Response Rate [ Time Frame: every 8 weeks until progression. Patients study participation will be 1 year from first dose of treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Histologically or cytologically-confirmed, HPV (+) or HPV (-) squamous cell carcinoma of the nasopharynx (WHO Type 1), oropharynx, hypopharynx, larynx (supraglottis, glottis, subglottis) or oral cavity,
  3. Recurrent or metastatic disease, documented by imaging (CT scan, MRI, X-ray) and/or physical examination. In phase II, measurable disease as per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 is mandated. In phase Ib, patients with or without measurable disease are eligible.
  4. Progression after platinum-based chemotherapy
  5. For phase Ib only: Pretreated patients, and not amenable to further therapy with curative intent. This part is open to pretreated patients regardless of the number of previous treatment lines.

    For phase II only: Patients who received a maximum of two prior systemic regimens for recurrent and/or metastatic disease and not amenable to further therapy with curative intent.

  6. No prior treatment by cetuximab except if given for primary treatment (locally advanced disease) with no progressive disease for at least 4 months following the end of prior cetuximab treatment.
  7. Recovery from prior surgery and recovery from adverse events to grade 1 or less (except alopecia) due to prior radiation therapy and any systemic therapy.
  8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  9. Life expectancy of ≥ 3 months
  10. Patients with treated brain metastases are eligible if they are > 4 weeks from therapy completion (including radiation and/or surgery), are clinically stable at the time of study entry and are not receiving corticosteroid therapy at the time of study entry
  11. Adequate hematologic, immunologic, liver and renal function, defined as

    • hemoglobin ≥ 9.0 g/dL,
    • absolute neutrophil count ≥ 1,500/mm3,
    • platelets ≥ 100,000/mm3,
    • total bilirubin ≤ 1.5 X institutional upper normal limit (UNL),
    • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X institutional UNL,
    • serum creatinine ≤1.5 X institutional UNL or estimated (Cockcroft-Gault formula) or measured creatinine clearance ≥ 50 mL/min
  12. Negative serum pregnancy test within 72 hours before starting study treatment for women of childbearing potential. Women of childbearing potential and all men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of monalizumab administration and for up to 5 months after the last dose of monalizumab.
  13. Ability to understand a written informed consent document
  14. Signed informed consent prior to any protocol-specific procedures

Exclusion Criteria:

  1. For phase II only: Patients who received more than 2 prior systemic regimens for recurrent and/or metastatic disease (no restriction in the phase Ib part of the trial).
  2. For phase II only: Patients who received cetuximab or another inhibitor of epidermal growth factor receptor are excluded from the phase II of the trial, except if cetuximab was given as part of a primary treatment approach, with no progressive disease for at least 4 months following the end of prior cetuximab treatment.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab.
  4. Patients with known untreated and uncontrolled brain metastases are excluded. However, brain-imaging studies are not required for eligibility if the patient has no neurological signs or symptoms.
  5. Serious concurrent uncontrolled medical disorder.
  6. Auto-immune disease, which:

    1. currently or previously required systemic immunosuppressive or immunomodulatory therapy (including corticosteroids administered by systemic route) and/or
    2. has a substantial probability to cause an irreversible injury to any tissue and/or
    3. has been diagnosed less than 3 months before study entry and/or
    4. is clinically unstable and/or
    5. has a substantial risk to progress and cause severe complications.
  7. Abnormal cardiac status with any of the following:

    1. Unstable angina
    2. Arrhythmia requiring treatment which is not stabilized by the treatment
    3. QTc > 450 ms (M) or 470 ms (F) (Bazett formula -QT Interval / √ (RR interval) where RR Interval = 60/HR).
  8. History of cardiac dysfunction including any of the following:

    1. Myocardial infarction within the last 6 months
    2. History of documented congestive heart failure (New York Heart Association functional classification III-IV).
  9. Known interstitial lung disease.
  10. Pregnant women are excluded from this study; breastfeeding must be discontinued.
  11. Other active invasive malignancy (except for treated basal or squamous cell skin carcinoma, or in situ cervix carcinoma).
  12. Treatment with other investigational agents less than 14 days prior to study entry.
  13. Systemic treatment with steroids or other immunosuppressive agents within 30 days prior to entry. Physiological replacement with hydrocortisone or equivalent is acceptable.
  14. Current active infectious disease.
  15. Positive serology for HIV.
  16. Positive HBs Ag or positive HBV viremia, Positive HCV viremia.
  17. Psychological, familial, sociological, or geographical conditions that do not permit medical follow-up and compliance with study protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02643550

Contact: Agnes Boyer Chammard, MD +33430303120
Contact: Anne Marie Soulie +33430303123

United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Roger Cohen, MD         
Centre Leon Berard Recruiting
Lyon, France
Contact: Jerome Fayette, MD         
Hopital La Timone Recruiting
Marseille, France
Contact: Sebastien Salas, MD         
Sponsors and Collaborators
Innate Pharma

Responsible Party: Innate Pharma Identifier: NCT02643550     History of Changes
Other Study ID Numbers: IPH2201-203
First Posted: December 31, 2015    Key Record Dates
Last Update Posted: April 23, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Antineoplastic Agents