Phase II Study of MEDI4736 Monotherapy in Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Phase 2

Completed

Conditions: Recurrent or Metastatic PD-L1-positive Squamous Cell Carcinoma of the Head and Neck

Interventions: Drug: MEDI4736

Registration Number: NCT02207530

Lead Sponsor: AstraZeneca

Brief Summary: Primary Objective: To assess the efficacy of MEDI4736 monotherapy in terms of ORR

Detailed Description: This is a phase II, multi-center, single-arm, global study of MEDI4736 monotherapy in patients with PD-L1 positive recurrent or metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN), who have progressed during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 112

Inclusion Criteria

Age ≥18 years
Written informed consent obtained from the patient/legal representative
Histologically confirmed recurrent or metastatic SCCHN
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.
Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
Confirmed PD-L1-positive SCCHN by Ventana SP263 assay
WHO/ECOG performance status of 0 or 1
At least 1 measurable lesion at baseline
No prior exposure to immune-mediated therapy
Adequate organ and marrow function
Evidence of post-menopausal status or negative urinary or serum pregnancy test.

Exclusion Criteria

Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck
Received more than 1 systematic palliative regimen for recurrent or metastatic disease
Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment
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
Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment
Major surgical procedure within 28 days prior to the first dose of Investigational Product
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
Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736
History of allogeneic organ transplantation
Active or prior documented autoimmune or inflammatory disorders;
Uncontrolled intercurrent illness
Another primary malignancy
Patients with history of brain metastases, spinal cord compression, or leptomeningeal carcinomatosis
History of active primary immunodeficiency
Known history of previous tuberculosis
Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
Receipt of live, attenuated vaccine within 30 days prior to the first dose of MEDI4736
Pregnant or breast-feeding female patients
Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MEDI4736	MEDI4736	MEDI4736 monotherapy

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	12 months	Objective response rate (per RECIST 1.1 as assessed by blinded independent central review \[BICR\]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1. criteria are: Complete response \[CR\] = disappearance of all target lesions since baseline; and partial response \[PR\] = at least a 30% decrease in the sum of the diameters of target lesions.

Secondary Outcome Measures

Name	Time	Method
Duration of Response	12 months	Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1. Duration of response was the time from the first documentation of complete or partial response until the date of progression (which was subsequently confirmed), death, or the last evaluable RECIST assessment for patients that did not progress. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Time to Onset of Response From First Dose	12 months	Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1
Best Objective Response	12 months	Best objective response based on BICR assessments according to RECIST v1.1. Response required confirmation after 4 weeks. Unconfirmed complete (CR) or partial response (PR) refers to CR or PR achieved but either no confirmation assessment was performed or a confirmation assessment was performed but response was not confirmed.
Progression-free Survival	12 months	Progression status based on BICR assessments according to RECIST v1.1 at time of PFS analysis. Progression was defined as the time from the date of first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression.
Duration of Response- Participants Remaining in Response	12 months	Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.
Quality of Life	12 months	Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: * The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3. * Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H\&N35. Function or global health status/quality of life improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (an increase from baseline score ≥10). Symptom improvement was defined as 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10). Scale improvement was defined as patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10).
Disease Control at 6 Months	6 months	Disease control (DCR) at 6 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD): * Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following the start of study treatment. * Method 2: Patients who had a best objective response of CR or PR within 24 weeks or had demonstrated SD for a minimum interval of 16 weeks following the start of study treatment.
Overall Survival (OS)	12 months	Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status, or who were lost to follow-up.