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

Study Overview
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Brief Summary
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The objective of this study is to evaluate in a 3 +3 design, the safety of escalating doses of Monalizumab 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). Cohorts expansion will evaluate antitumor activity of monalizumab and cetuximab with or without anti-PD(L)1

Official Title
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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

Conditions
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Head and Neck Neoplasms

Intervention / Treatment
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* Biological: Monalizumab
* Biological: Cetuximab
* Biological: Anti-PD(L)1


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Age ≥ 18 years 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. Recurrent or metastatic disease, documented by imaging (CT scan, MRI, X-ray) and/or physical examination with measurable disease as per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 For phase II cohorts: Cohort #1: 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 Cohort #2: Patients with R/M SCCHN not amenable to therapy of curative intent, who have received a maximum of two prior systemic regimens in the R/M setting and who have received prior PD-(L)1 blockers Cohort #3: Patients with R/M SCCHN who have not received prior systemic regimens in the R/M setting and who have not received prior PD-(L)1 inhibitors Main Exclusion Criteria: For phase II cohort #1 and cohort #2: 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). For phase II cohort #1 and cohort #2: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>Dose escalation of monalizumab in combination with cetuximab | Biological: Monalizumab<br> <br> * Other names: IPH2201;Biological: Cetuximab<br> <br> |
| Experimental: Expansion cohort 1<br>monalizumab + cetuximab expansion cohort | Biological: Monalizumab<br> <br> * Other names: IPH2201;Biological: Cetuximab<br> <br> |
| Experimental: Expansion cohort 2<br>monalizumab + cetuximab expansion cohort in patients with prior exposure to PD-(L)1 blockers | Biological: Monalizumab<br> <br> * Other names: IPH2201;Biological: Cetuximab<br> <br> |
| Experimental: Expansion cohort 3<br>monalizumab + cetuximab + anti-PD(L)1 | Biological: Monalizumab<br> <br> * Other names: IPH2201;Biological: Cetuximab<br> <br> Biological: Anti-PD(L)1<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Dose Limiting Toxicities (DLT) in the dose escalation part of the study | To assess the occurrence of Drug Limited Toxicities (DLTs) | within 4 weeks after first administration | 
| Objective Response Rate for expansion cohorts | rate of patients in complete or partial response according to RECIST 1.1. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate for dose escalation part of the study | rate of patients in complete or partial response according to RECIST 1.1 | up to 12 months | 
| Duration of Response for expansion cohorts | Duration of complete and partial response | From confirmed response until disease progression, up to 12 months | 
| Progression Free Survival for expansion cohorts | time between the start of treatment and the first documented progression or death | Until disease progression or death, up to 2 years | 
| Overall Survival for expansion cohorts | time between the start of treatment and death | Until death, up to 2 years |