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 (INTERLINK-1)
- Conditions
- cancer of head and necksquamous cell carcinoma of the head and neck10027655
- Registration Number
- NL-OMON56351
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 23
1. Participant must be >= 18 years of age at the time of signing the informed
consent.
2. Histologically or cytologically confirmed R/M SCCHN of the oral cavity,
oropharynx, hypopharynx, or larynx who have progressed on or after previous
systemic cancer therapy and are not amenable to curative therapy
3. Must have received prior treatment with a systemic PD-(L)1 inhibitor (in any
setting)
4. Prior platinum failure as defined in the protocol.
5. Received 1 or 2 prior systemic regimens for R/M SCCHN
6. At least one measurable lesion by RECIST 1.1 at baseline. Tumor assessment
by CT scan or MRI must be performed within 28 days prior to randomization.
7. Provide fresh or recently acquired tumor tissue (<= 3 months prior to
screening) for the purpose of biomarker testing.
8. For participants with OPC only: known HPV status prior to randomization
9. WHO/ECOG PS of 0 or 1 at enrollment
10. Adequate organ function (see definition in the protocol)
11. Minimum life expectancy of 12 weeks
12. Body weight > 30 kg
13. Male and/or female
14. Negative pregnancy test for female participants of childbearing potential.
15. Female participants must be one year post-menopausal, surgically sterile,
or using an acceptable method of contraception
16. Male participants must be surgically sterile or using an acceptable method
of contraception
17. Capable of giving signed informed consent
18. Provision of signed and dated, written ICF prior to any mandatory study
specific procedures, sampling, and analyses
19. Provision of signed and dated written informed consent for genetic sample
and analysis (optional)
20. Provision of signed and dated written Optional Genetic Research Information
informed consent prior to collection of samples for optional genetic research
that supports Genomic Initiative
1. Histologically or cytologically confirmed head and neck cancer of any other
primary
anatomic location in the head and neck not specified in the inclusion criteria
including
participants with squamous cell carcinoma of unknown primary or non-squamous
histologies (eg, nasopharynx or salivary gland)
2. Prior cetuximab therapy (unless in Locally Advanced setting with
radiotherapy and no disease progression for at least 6 months following the
last cetuximab
dose)
3. Any unresolved toxicity NCI CTCAE >= Grade 2 from previous anticancer therapy
with
the exception of alopecia, vitiligo, and the laboratory values defined in the
inclusion criteria.
4. Has carcinomatous meningitis and/or untreated central nervous system
metastases identified either on the baseline brain imaging obtained during the
screening period or identified prior to signing the ICF.
5. Major surgical procedure (as defined by the investigator) within 28 days
prior to the first
dose of study intervention
6. History of allogeneic organ transplantation
7. History of allergic reactions or hypersensitivity attributed to compounds of
similar chemical or biologic composition to cetuximab and monalizumab or any of
their excipients
8. History of active primary immunodeficiency
9. Active or prior documented autoimmune or inflammatory disorders
10. Active infection including tuberculosis, hepatitis B, hepatitis C, or human
immunodeficiency virus
11. Uncontrolled intercurrent illness
12. History of another primary malignancy
13. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF)
>= 500 ms
calculated from 3 ECGs
14. Any concurrent anticancer treatment
15. Receipt of the last dose of anticancer therapy or radiotherapy with
curative intent <= 28 days prior to the first dose of study intervention.
16. Current or prior use of immunosuppressive medication within 14 days before
the first dose of study intervention.
17. Receipt of live attenuated vaccine within 30 days prior to the first dose
of study intervention.
18. Participation in another clinical study with an investigational product
administered in the
last 28 days prior to randomization or concurrent enrollment in another
clinical study
19. Prior treatment with monalizumab
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary:<br /><br>- To compare the effect of monalizumab and cetuximab (Arm A) relative to<br /><br>placebo and cetuximab (Arm B) by assessment of OS in HPV-unrelated<br /><br>participants.<br /><br><br /><br>• Population: The primary population is the HPV-unrelated Analysis Set which<br /><br>will include all randomized participants who are either OPC HPV negative or<br /><br>non-OPC regardless of the HPV status.<br /><br>• Endpoint: OS, which is defined as time from randomization until the date of<br /><br>death due to any cause<br /><br>• Intercurrent events: If a participant is lost to follow-up or withdraws<br /><br>consent, OS will be censored based on the last recorded date on which the<br /><br>participant was known to be alive<br /><br>• Summary measure: p-value of treatment comparison using a stratified log rank<br /><br>test and hazard ratio of Arm A relative to Arm B with its confidence interval<br /><br>using a stratified Cox Proportional Hazards model</p><br>
- Secondary Outcome Measures
Name Time Method