Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer (INTERLINK-1)
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| ClinicalTrials.gov Identifier: NCT04590963 |
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Recruitment Status :
Active, not recruiting
First Posted : October 19, 2020
Results First Posted : November 18, 2023
Last Update Posted : March 4, 2024
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Sponsor:
AstraZeneca
Collaborator:
Innate Pharma
Information provided by (Responsible Party):
AstraZeneca
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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 Participants with recurrent or metastatic head and neck cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Squamous Cell Carcinoma of the Head and Neck | Drug: Monalizumab Drug: Cetuximab Other: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 370 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Parallel study. Participants 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 : | October 2, 2020 |
| Actual Primary Completion Date : | May 11, 2022 |
| Estimated Study Completion Date : | June 28, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Head and neck squamous cell carcinoma
Drug Information
available for:
Cetuximab
| Arm | Intervention/treatment |
|---|---|
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Experimental: Monalizumab 750 mg Q2W + Cetuximab 400 mg/m^2
Participants will receive intravenous (IV) monalizumab 750 mg every two weeks (Q2W) and IV cetuximab 400 mg/m^2 initial dose followed by 250 mg/m^2 every one week (Q1W) until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
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Drug: Monalizumab
Participants will receive IV infusion of monalizumab as stated in arm description.
Other Name: IPH2201 Drug: Cetuximab Participants will receive IV infusion of cetuximab as stated in arm description.
Other Name: Erbitux |
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Active Comparator: Placebo Q2W + Cetuximab 400 mg/m^2
Participants will receieve IV placebo matched to monalizumab Q2W and IV cetuximab 400 mg/m^2 initial dose followed by 250 mg/m^2 Q1W until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.
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Drug: Cetuximab
Participants will receive IV infusion of cetuximab as stated in arm description.
Other Name: Erbitux Other: Placebo Participants will receive IV infusion of placebo as stated in arm description. |
Primary Outcome Measures :
- Overall Survival (OS) in Human Papillomavirus (HPV)-Unrelated Analysis Set [ Time Frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration) ]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).
Secondary Outcome Measures :
- Overall Survival in Full Analysis Set (FAS) [ Time Frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration) ]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).
- Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment in HPV-unrelated Analysis Set [ Time Frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration) ]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.
- Progression-Free Survival Per RECIST 1.1 by Investigator Assessment in FAS [ Time Frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration) ]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.
- Percentage of Participants With Objective Response (OR) Per RECIST 1.1 in HPV-unrelated Analysis Set [ Time Frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration) ]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.
- Percentage of Participants With OR Per RECIST 1.1 in FAS [ Time Frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration) ]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.
- Duration of Response (DoR) Per RECIST 1.1 in HPV-unrelated Analysis Set [ Time Frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration) ]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.
- Duration of Response Per RECIST 1.1 in FAS [ Time Frame: Baseline (-28 to -1) through 17.5 months (maximum observed duration) ]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.
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 through 21.4 months (maximum observed duration) ]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.
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [ Time Frame: Day 1 through 21.4 months (maximum observed duration) ]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.
- Number of Participants With Abnormal Vital Signs Reported as TEAEs [ Time Frame: Day 1 through 21.4 months (maximum observed duration) ]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.
- Number of Participants With Electrocardiograms (ECGs) Reported as TEAEs [ Time Frame: Day 1 through 21.4 months (maximum observed duration) ]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.
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| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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)
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 ClinicalTrials.gov identifier (NCT number): NCT04590963
Locations
Show 127 study locations
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)
Documents provided by AstraZeneca:
Documents provided by AstraZeneca:
Study Protocol [PDF] July 7, 2021
Statistical Analysis Plan [PDF] July 19, 2022
Additional Information:
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04590963 |
| Other Study ID Numbers: |
D7310C00001 2019-004770-25 ( EudraCT Number ) |
| First Posted: | October 19, 2020 Key Record Dates |
| Results First Posted: | November 18, 2023 |
| Last Update Posted: | March 4, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of the timelines, please refer to the disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| Access Criteria: | When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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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:
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Carcinoma Carcinoma, Squamous Cell Squamous Cell Carcinoma of Head and Neck Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms |
Neoplasms, Squamous Cell Head and Neck Neoplasms Neoplasms by Site Cetuximab Antineoplastic Agents, Immunological Antineoplastic Agents |