None listed
Conditions
Interventions
Monalizumab 750 mg iv Q2W and cetuximab 400 mg/m2 iv initial dose followed by 250 mg/m2 iv Q1W, as per label
Group name:Arm B Type of group
Placebo iv Q2W and cetuximab 400 mg/m2 iv initial dose followed by 250 mg/m2 iv Q1W, as per label
Sponsors
AstraZeneca AB,
Eligibility
Inclusion criteria
Inclusion criteria: Age 1 Participant must be ≥ 18 years of age at the time of signing the informed consent. Type of Participant and Disease Characteristics 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 by either:  Disease progression during or after treatment with a platinum-containing regimen for R/M disease or  Recurrence/progression within 6 months of the last dose of platinum as part of multimodal therapy for LA disease 5 Received 1 or 2 prior systemic regimens for R/M SCCHN 6 At least one lesion that qualifies as a RECIST 1.1 TL 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. Tumor tissue collected when previous treatments were still ongoing is not acceptable.  Tumor tissue beyond the 3-month window and up to 6 months old may be considered with Sponsor consultation provided that no intervening systemic regimen was ongoing. 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, defined as: (a) Hemoglobin ≥ 9.0 g/dL (b) Absolute neutrophil count ≥ 1500/mm3 (c) Platelets ≥ 75,000/mm3 (d) Total bilirubin ≤ 1.5 × institutional ULN. This will not apply to participants with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician. (e) Aspartate aminotransferase and ALT ≤ 2.5 × institutional ULN; for participants with hepatic metastases, ALT and AST ≤ 5 × ULN (f) Measured CrCL ≥ 30 mL/min or calculated CrCL ≥ 30 mL/min as determined by Cockcroft-Gault (using actual body weight) o Males: CrCL(mL/min) = Weight (kg) × (140 - age) 72 × serum creatinine (mg/dL) o Females: CrCL (mL/min) = Weight (kg) × (140 - age) × 0.85 72 × serum creatinine (mg/dL) 11 Minimum life expectancy of 12 weeks Weight 12 Body weight > 30 kg Sex 13 Male and/or female Reproduction 14 Negative pregnancy test (“highly effective” urine or serum 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 (see Appendix G) for the duration of the study (from the time they sign consent) and for 4 months after the last dose of study intervention to prevent pregnancy. 16 Male participants must be surgically sterile or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 4 months after the last dose of study intervention to prevent pregnancy in a female partner. Male participants must not donate or bank sperm during the same time period. Informed Consent 17 Capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol 18 Provision of signed and dated, writt
Exclusion criteria
Exclusion criteria: Medical Conditions 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 it was administered in curative LA 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.  Participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with monalizumab and cetuximab may be included only after consultation with the Medical Monitor. 4 Has carcinomatous meningitis and/or untreated central nervous system metastases identified either on the baseline brain imaging (see Appendix F) obtained during the screening period or identified prior to signing the ICF. Participants with a history of brain metastases or with suspected brain metastases at screening must have an MRI (preferred) or CT each preferably with iv contrast of the brain prior to study entry. Participants whose brain metastases have been treated may participate provided they show radiographic stability (defined as 2 brain images, both of which are obtained after treatment to the brain metastases. These imaging scans should both be obtained at least 4 weeks apart and show no evidence of intracranial progression). In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of ≤ 10 mg/day of prednisone or its equivalent and anticonvulsants for at least 14 days prior to the start of treatment. Brain metastases will not be recorded as RECIST 1.1 TL at baseline. 5 Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study intervention. Note: Local surgery of isolated lesions for palliative intent is acceptable. 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 (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:  Participants with vitiligo or alopecia  Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement  Any chronic skin condition that does not require systemic therapy  Participants without active disease in the last 5 years may be included but only after consultation with the Medical Monitor  Participants with celiac disease controlled by diet alone 10 Active infection including tuberculosis (
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:Comparison in the effect of monalizumab and cetuximab (Arm A) relative to placebo and cetuximab (Arm B) by assessment of OS Measure:Overall Survival (OS), which is defined as time from randomization until the date od death due to any cause Timepoints:Since randomization til death or lost to follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:per RECIST 1.1 as assessed by Investigator Measure:• PFS (progressionfree survival) is defined as time from randomization until disease progression • ORR (objective response rate) is defined as the proportion of participants with measurable disease who have a confirmed Complete response or Partial Response • DoR (duration of response) 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. Timepoints:Since randomization until documented disease progression or death ; Outcome name:per scores in quality of life questionnaires Measure:Symptoms, functioning, and global health status/QoL scale/item scores of the EORTC QLQC30 & EORTC QLQ-H&N35 • Change from baseline scores across visits • Time to clinically meaningful deterioration in scores Timepoints:from randomization until disease progression or death ; Outcome name:per central sample lab tests Measure:Concentration of monalizumab in blood and PK parameters Timepoints:from randomization until disease progression or death ; Outcome name:per central sample lab tests Measure:Presence of ADAs for monalizumab Timepoints:from randomization until disease progression or death ; Outcome name:per central sample lab tests Measure:HLA-E and NKp46+ expression in pre-treatment and post-treatment tumor biopsies Timepoints:from randomization until disease progression or death | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, France, Germany, Greece, Italy, Japan, Korea South, Netherlands, Philippines, Poland, Portugal, Romania, Russian Federation, Spain, Switzerland, Taiwan, Thailand, United Kindgdom, United States
Contacts
Public ContactUrsula Rodriguez-Frias
ASTRAZENECA PERU S.A.
Outcome results
None listed