Description:
This is a randomized, double-blind, multicenter, global Phase 3 study to assess the efficacy
and safety of monalizumab and cetuximab, compared to placebo and cetuximab, in patients with
recurrent or metastatic head and neck cancer.
Title
- Brief Title: Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer
- Official Title: A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination With Cetuximab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor
Clinical Trial IDs
- ORG STUDY ID:
D7310C00001
- NCT ID:
NCT04590963
Conditions
- Squamous Cell Carcinoma of the Head and Neck
Interventions
| Drug | Synonyms | Arms |
|---|
| Monalizumab | | Arm A (monalizumab and cetuximab) |
| Cetuximab | Erbitux | Arm A (monalizumab and cetuximab) |
Purpose
This is a randomized, double-blind, multicenter, global Phase 3 study to assess the efficacy
and safety of monalizumab and cetuximab, compared to placebo and cetuximab, in patients with
recurrent or metastatic head and neck cancer.
Detailed Description
Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)
who had prior immune checkpoint inhibitor and platinum-based chemotherapy treatment will be
randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab. Efficacy and
safety assessments will be performed periodically from the time of enrollment and throughout
the study. Patients in all arms will continue therapy until progression, unacceptable
toxicity, withdrawal of consent, or another discontinuation criterion is met. All patients
will be followed for survival after progression is confirmed.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A (monalizumab and cetuximab) | Experimental | monalizumab in combination with cetuximab | |
| Arm B (placebo and cetuximab) | Active Comparator | placebo in combination with cetuximab | |
Eligibility Criteria
Inclusion Criteria:
- Are aged 18 years and over
- Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), (oral
cavity, oropharynx, hypopharynx, or larynx) which has progressed on or after previous
systemic cancer therapy and is not amenable to curative therapy
- Received prior treatment using a PD-(L)1 inhibitor
- Prior platinum failure
- Received 1 or 2 prior systemic regimens for recurrent or metastatic SCCHN
- Has measurable disease per RECIST 1.1
- A fresh or recently acquired tumor tissue for the purpose of biomarker testing
- World Health Organization (WHO)/ Eastern Cooperative Oncology Group (ECOG) Performance
Status of 0 or 1
Exclusion Criteria:
- Head and neck cancer of any primary anatomic location in the head and neck not
specified in the inclusion criteria, including participants with SCCHN of unknown
primary or non-squamous histologies
- Had prior cetuximab therapy (unless it was administered in curative locally advanced
setting with radiotherapy and no disease progression for at least 6 months following
the last cetuximab dose)
- Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis
- Any concurrent anticancer treatment, except for hormonal therapy for
non-cancer-related conditions (eg, hormone replacement therapy)
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Overall Survival (OS) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Overall survival, defined as the time from the date of randomization until date of death due to any cause, in HPV-unrelated participants. |
Secondary Outcome Measures
| Measure: | Overall Survival (OS) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Overall survival, defined as the time from the date of randomization until date of death due to any cause, in all randomized participants |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | PFS is defined as time from randomization until disease progression, per RECIST 1.1 as assessed by the investigator at local site or death due to any cause, whichever occurs first. |
| Measure: | Disease-related symptoms, functioning and quality of life measured by EORTC QLQ-C30 questionnaire |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | EORTC QLQ-C30 questionnaire to measure cancer patients' functioning (HRQoL) and symptoms. It consists of functional, symptom and a global measure of health status scales. |
| Measure: | Immunogenicity of monalizumab |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Presence of ADAs for monalizumab (confirmatory results: positive or negative, titers). |
| Measure: | Association of NK cell-related protein markers with efficacy endpoints including OS, PFS, and ORR |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | The level of protein expression related to Natural Killer cell-mediated immune response will be evaluated in relation to OS, PFS, and ORR outcomes. |
| Measure: | Assessment of Adverse Events (AE) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Assessment of AEs by CTCAE v 5.0 as measures of the safety and tolerability of monalizumab plus cetuximab as compared to placebo plus cetuximab. |
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | ORR is defined as the proportion of participants with measurable disease who have a confirmed CR or PR, as determined by the investigator at local site per RECIST 1.1. |
| Measure: | Duration of Response (DoR) |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | DoR is defined as the time from the date of first documented response until date of documented disease progression or death in the absence of disease progression. |
| Measure: | Disease-related symptoms, functioning and quality of life measured by EORTC QLQ-H&N35 questionnaire |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | EORTC QLQ-H&N35 questionnaire to measure head and neck cancer patients' functioning (HRQoL) and symptoms. It consists of functional, symptom and a global measure of health status scales. |
| Measure: | Pharmacokinetics (PK) analysis of monalizumab |
| Time Frame: | Approximately 3 years |
| Safety Issue: | |
| Description: | Measurement of the monalizumab concentration in blood. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AstraZeneca |
Trial Keywords
- head and neck cancer
- Squamous Cell Carcinoma of the Head and Neck
- monalizumab
- cetuximab
- Erbitux
- oral cavity
- larynx
- pharynx
- natural killer
- oropharynx
- hypopharynx
Last Updated
August 31, 2021
