Patients with recurrent or metastatic PD-L1-negative squamous cell carcinoma of the head and neck (SCCHN) MedDRA version: 20.0 Level: PT Classification code 10067821 Term: Head and neck cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MEDI4736
Product Code: MEDI4736
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not applicable
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Other descriptive n
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age =18 years at the time of screening; 2) Written informed consent and any locally required authorization; 3) Histologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Patients who refuse radical resection are eligible; 4) Tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent. Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible. Patients who received concurrent chemo-radiation as part of treatment of their recurrent disease are also not eligible; 5) Able and willing to give valid written consent to provide newly acquired tumor tissue (preferred) or archival tissue (=65 years) yes F.1.3.1 Number of subjects for this age range 144
Exclusion criteria
Exclusion criteria: 1) Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck, patients with squamous cell carcinoma of the head and neck of unknown primary, and non squamous histologies; 2) Received more than 1 systemic palliative regimen for recurrent or metastatic disease; 3) Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable; 4) Prior randomization or treatment in a previous MEDI4736 and/or tremelimumab clinical study regardless of treatment arm assignment or receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment; 5) Receipt of last dose of an approved (marketed) anticancer therapy within 21 days prior to the first dose of study treatment. If sufficient washout time has not occurred due to the schedule or PK properties of an agent, a longer washout period will be required, as agreed upon by AstraZeneca and the Investigator; 6) Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable; 7) 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 criterion: *- Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the Study Physician, **- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with their assigned IP may be included after consultation with the Study Physician; 8) Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned IP. The following are exceptions to this criterion: * - Intranasal, inhaled, topical steroids, or local steroid injections, ** - Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent, *** - Steroids as pre-medication for hypersensitivity reactions; 9) History of allogeneic organ transplantation; 10) Active or prior documented autoimmune or inflammatory disorders (eg, including inflammatory bowel disease, diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, , or other serious GI chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener syndrome; myasthenia gravis; Graves’ disease; rheumatoid arthritis, hypophysitis, uveitis, etc) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: * - Patients with vitiligo or alopecia, ** - Patients with hypothyroidism stable on hormone replacement or other chronic skin conditions not requiring systemic treatment; 11) Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness or social situations that would limit compliance with study requirements, substantially increase the risk of incurring AEs from MEDI4736 or tremelimumab, or compromise the ability of the patient to give written informed consent; 12) History of another primary malignancy except for: * - Malignancy treated with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of MEDI4736 + tremelimumab combination therapy in terms of ORR;Secondary Objective: To further assess the efficacy of MEDI4736 + tremelimumab combination therapy in terms of ORR, TTR, DoR, DCR, BoR, PFS, and OS; To assess the efficacy of MEDI4736 + tremelimumab combination therapy compared with a) MEDI4736 monotherapy and b) tremelimumab monotherapy, in terms of ORR, PFS and OS; To explore symptoms and health-related QoL in patients with MEDI4736 monotherapy, tremelimumab monotherapy, and MEDI4736 + tremelimumab combination therapy using the EORTC QLQ-C30 v3 and the H&N35 module ;Primary end point(s): The primary endpoint is ORR. ORR is defined as the number (%) of patients with a confirmed overall response of CR (complete response) or PR (partial response) and will be based on all treated patients who have measurable disease at baseline per BICR (Evaluable Analysis Set). A confirmed response of CR/PR means that a response of CR/PR is recorded at one visit and confirmed by repeat imaging not less than 4 weeks after the visit when the response was first observed with no evidence of progression between the initial and CR/PR confirmation visit. Therefore, data obtained up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR. Any patient who discontinues treatment without progression, receives a subsequent therapy, and then responds will not be included as responders in the ORR.;Timepoint(s) of evaluation of this end point: The initial data cut-off will take place approximately 6 months after the last patient is first dosed. All study endpoints will be analyzed at this time with the exception of OS (overall survival). A further analysis of all study endpoints including OS will take place approximately 12 months after the last patient is dosed. A final analysis of OS and safety will be conducted approximately 18 months after the last patient is dosed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Duration of response (DoR) will be defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. The end of response should coincide with the date of progression or death from any cause used for the RECIST 1.1 PFS (Progression-free survival) endpoint. The denominator for DoR will be defined as described for ORR. 2) Disease control rate (DCR) at 4, 6 or 12 months is defined as the percentage of patients who have a BoR of CR or PR in the first 4, 6, or 12 months, respectively, or who have demonstrated SD (Stable disease) for a minimum interval of 16, 24, or 52 weeks, following randomization. As additional analysis, DCR at 6 months will also be assessed as % of patients who have a BoR of CR or PR in the first 6 months or who have demonstrated SD for a minimum interval of 12 weeks following randomization. 3) Progression-free survival (PFS) will be defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment. 4) Overall survival (OS) is defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive. Survival calls will be made in the week following the date of data cut-off (DCO) for the analysis, and if patients are confirmed to be alive or if the death date is post the DCO date, these patients will be censored at the date of DCO. Death dates may be found by checking publicly available death | — |
Countries
Belgium, Canada, Czech Republic, France, Germany, Hungary, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Transparency
AstraZeneca AB
Outcome results
None listed