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INTERLINK-1: Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04590963
Collaborator
Innate Pharma (Industry)
624
Enrollment
205
Locations
2
Arms
41.8
Anticipated Duration (Months)
3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
624 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Parallel study. Patients will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab.Parallel study. Patients will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double blinded study
Primary Purpose:
Treatment
Official Title:
A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination With Cetuximab in Participants With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor
Actual Study Start Date :
Oct 2, 2020
Anticipated Primary Completion Date :
Mar 28, 2024
Anticipated Study Completion Date :
Mar 28, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm A (monalizumab and cetuximab)

monalizumab in combination with cetuximab

Drug: Monalizumab
Monalizumab (intravenous)

Drug: Cetuximab
Cetuximab (intravenous)
Other Names:
  • Erbitux

    		•
    Active Comparator: Arm B (placebo and cetuximab)

    placebo in combination with cetuximab

    Drug: Cetuximab
    Cetuximab (intravenous)
    Other Names:
  • Erbitux

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Survival (OS) [Approximately 3 years]

      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

    1. Overall Survival (OS) [Approximately 3 years]

      Overall survival, defined as the time from the date of randomization until date of death due to any cause, in all randomized participants

    2. Progression Free Survival (PFS) [Approximately 3 years]

      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.

    3. Disease-related symptoms, functioning and quality of life measured by EORTC QLQ-C30 questionnaire [Approximately 3 years]

      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.

    4. Immunogenicity of monalizumab [Approximately 3 years]

      Presence of ADAs for monalizumab (confirmatory results: positive or negative, titers).

    5. Association of NK cell-related protein markers with efficacy endpoints including OS, PFS, and ORR [Approximately 3 years]

      The level of protein expression related to Natural Killer cell-mediated immune response will be evaluated in relation to OS, PFS, and ORR outcomes.

    6. Assessment of Adverse Events (AE) [Approximately 3 years]

      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.

    7. Objective Response Rate (ORR) [Approximately 3 years]

      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.

    8. Duration of Response (DoR) [Approximately 3 years]

      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.

    9. Disease-related symptoms, functioning and quality of life measured by EORTC QLQ-H&N35 questionnaire [Approximately 3 years]

      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.

    10. Pharmacokinetics (PK) analysis of monalizumab [Approximately 3 years]

      Measurement of the monalizumab concentration in blood.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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)

    Contacts and Locations

    Locations

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    Sponsors and Collaborators

    • AstraZeneca
    • Innate Pharma

    Investigators

    • Principal Investigator: Roger B Cohen, MD, Abramson Cancer Center, Perelman Center for Advanced Medicine
    • Principal Investigator: Jérôme Fayette, MD, Centre Leon Berard
    • Study Director: Dario Ruscica, MD, AstraZeneca, Cambridge, UK

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT04590963
    Other Study ID Numbers:
    • D7310C00001
    First Posted:
    Oct 19, 2020
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    head and neck cancer
    Squamous Cell Carcinoma of the Head and Neck
    monalizumab
    cetuximab
    Erbitux
    oral cavity
    larynx
    pharynx
    natural killer
    oropharynx
    hypopharynx
    Additional relevant MeSH terms:
    Carcinoma
    Carcinoma, Squamous Cell
    Squamous Cell Carcinoma of Head and Neck
    Cetuximab

    Study Results

    No Results Posted as of Jul 26, 2022