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

Squamous Cell Carcinoma of the Head and Neck Clinical Trial

— INTERLINK-1  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04590963
• Other study ID #: D7310C00001
• Secondary ID: 2019-004770-25
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 2, 2020
• Est. completion date: June 28, 2024

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 Participants with recurrent or metastatic head and neck cancer.

Description:

Participants 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. Participants in all arms will continue therapy until progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. All Participants will be followed for survival after progression is confirmed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 370
• Est. completion date: June 28, 2024
• Est. primary completion date: May 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Are aged 18 years and over

• Recurrent or metastatic squamous cell carcinoma of the 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 programmed cell death ligand-1 (PD-L1) 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)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma of Head and Neck
• Squamous Cell Carcinoma of the Head and Neck

Intervention

Drug:
• Monalizumab
Participants will receive IV infusion of monalizumab as stated in arm description.
• Cetuximab
Participants will receive IV infusion of cetuximab as stated in arm description.

Other:
• Placebo
Participants will receive IV infusion of placebo as stated in arm description.

Locations

Country	Name	City	State
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Australia	Research Site	Camperdown
Australia	Research Site	Elizabeth Vale
Australia	Research Site	Heidelberg
Australia	Research Site	Melbourne
Austria	Research Site	Linz
Belgium	Research Site	Bruxelles
Belgium	Research Site	Leuven
Belgium	Research Site	Namur
Belgium	Research Site	Roeselare
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Bulgaria	Research Site	Panagyurishte
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Victoria	British Columbia
France	Research Site	Avignon
France	Research Site	Bordeaux
France	Research Site	Clermont Ferrand cedex 01
France	Research Site	Dijon
France	Research Site	Lyon Cedex 08
France	Research Site	Marseille
France	Research Site	Montpellier Cedex 05
France	Research Site	Strasbourg
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Freiburg
Germany	Research Site	Hannover
Germany	Research Site	Leipzig
Germany	Research Site	Ulm
Germany	Research Site	Würzburg
Greece	Research Site	Athens
Greece	Research Site	Chaidari
Greece	Research Site	Thessaloniki
Italy	Research Site	Brescia
Italy	Research Site	Candiolo
Italy	Research Site	Firenze
Italy	Research Site	Milano
Italy	Research Site	Milano
Italy	Research Site	Modena
Italy	Research Site	Napoli
Italy	Research Site	Padova
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kashiwa
Japan	Research Site	Kobe-shi
Japan	Research Site	Koto-ku
Japan	Research Site	Okayama
Japan	Research Site	Osakasayama
Japan	Research Site	Sunto-gun
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Cheongju-si
Korea, Republic of	Research Site	Goyang-si
Korea, Republic of	Research Site	Seongnam-si
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Maastricht
Netherlands	Research Site	Nijmegen
Philippines	Research Site	Manila
Philippines	Research Site	Pasig City
Philippines	Research Site	Quezon City
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Poznan
Portugal	Research Site	Coimbra
Portugal	Research Site	Porto
Portugal	Research Site	Porto
Portugal	Research Site	Vila Nova de Gaia
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow region
Russian Federation	Research Site	Obninsk
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St.Petersburg
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Switzerland	Research Site	Basel
Switzerland	Research Site	Bern
Switzerland	Research Site	Lausanne
Taiwan	Research Site	Changhua
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Newcastle upon Tyne
United Kingdom	Research Site	Sutton
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Boston	Massachusetts
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Columbus	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	New York	New York
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Rochester	Minnesota
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Tucson	Arizona
United States	Research Site	Westwood	Kansas
United States	Research Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Innate Pharma

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Philippines,  Poland,  Portugal,  Russian Federation,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in Human Papillomavirus (HPV)-Unrelated Analysis Set	The OS is defined as time from the date of randomization until death due to any cause regardless of whether the participant withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization + 1). The OS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and hazard ratio (HR) and confidence intervals (CIs) from a stratified Cox proportional hazards model. Analyses were stratified on World Health Organization/ Eastern Cooperative Oncology Group performance status (WHO/ECOG PS) (0 or 1) and number of prior lines of therapy in recurrent or metastatic (R/M) setting (1 or 2).	Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary	Overall Survival in Full Analysis Set (FAS)	The OS is defined as time from the date of randomization until death due to any cause regardless of whether the participant withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization + 1). The OS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on HPV status (OPC HPV positive or HPV-unrelated), WHO/ECOG PS (0 or 1) and number of prior lines of therapy in R/M setting (1 or 2).	Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary	Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment in HPV-unrelated Analysis Set	PFS per RECIST 1.1 as assessed by the investigator is defined as time from randomization until date of RECIST 1.1-defined radiological progressive disease (PD) or death regardless of whether participant withdraws from therapy or received subsequent anticancer therapy prior to progression. PD: at least 20% increase in sum of diameters of target lesions (TLs), taking as reference the smallest sum on study (nadir) and sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing non-TLs (NTLs) or appearance of new lesions. PFS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on WHO/ECOG PS (0/1) and no. of prior lines of therapy in R/M setting.	Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary	Progression-Free Survival Per RECIST 1.1 by Investigator Assessment in FAS	PFS per RECIST 1.1 as assessed by the investigator is defined as time from randomization until date of RECIST 1.1-defined radiological progressive disease (PD) or death regardless of whether participant withdraws from therapy or received subsequent anticancer therapy prior to progression. PD: at least 20% increase in sum of diameters of target lesions (TLs), taking as reference the smallest sum on study (nadir) and sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing NTLs or appearance of new lesions. PFS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on HPV status, WHO/ECOG PS (0/1) and no. of prior lines of therapy in R/M setting.	Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary	Percentage of Participants With Objective Response (OR) Per RECIST 1.1 in HPV-unrelated Analysis Set	The OR is defined as the percentage of participants with at least one confirmed investigator-assessed response of complete response (CR) or partial response (PR) as assessed by RECIST 1.1 guidelines. The CR is defined as disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the sum of the diameters (SoD) of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.	Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary	Percentage of Participants With OR Per RECIST 1.1 in FAS	The OR is defined as the percentage of participants with at least one confirmed investigator-assessed response of CR or PR as assessed by RECIST 1.1 guidelines. The CR is defined as disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis < 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.	Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary	Duration of Response (DoR) Per RECIST 1.1 in HPV-unrelated Analysis Set	The DoR is defined as the time from the date of first documented confirmed response until date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the SoDs of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest previous SoDs (nadir) and the sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing NTLs or appearance of new lesions. The DoR was analyzed using Kaplan-Meier technique.	Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary	Duration of Response Per RECIST 1.1 in FAS	The DoR is defined as the time from the date of first documented confirmed response until date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the SoDs of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest previous SoDs (nadir) and the sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing NTLs or appearance of new lesions. The DoR was analyzed using Kaplan-Meier technique.	Baseline (-28 to -1) through 17.5 months (maximum observed duration)
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.	Day 1 through 21.4 months (maximum observed duration)
Secondary	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs	Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology and clinical chemistry. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.	Day 1 through 21.4 months (maximum observed duration)
Secondary	Number of Participants With Abnormal Vital Signs Reported as TEAEs	Participants with abnormal vital signs (heart rate, blood pressure, temperature, and respiratory rate) reported as TEAEs are reported. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.	Day 1 through 21.4 months (maximum observed duration)
Secondary	Number of Participants With Electrocardiograms (ECGs) Reported as TEAEs	Participants with Abnormal ECGs reported as TEAEs are reported. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.	Day 1 through 21.4 months (maximum observed duration)

External Links

•   Redacted CSR synopsis
•   Redacted Statistical Analysis Plan
•   Redacted Study Protocol