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

• ClinicalTrials.gov Identifier: NCT02207530
• Recruitment Status: Completed
• First Posted: August 4, 2014
• Results First Posted: June 18, 2018
• Last Update Posted: September 29, 2020
• Sponsor: AstraZeneca
• Collaborator: PRA Health Sciences
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: August 1, 2014
• First Posted Date: August 4, 2014
• Results First Submitted Date: March 26, 2018
• Results First Posted Date: June 18, 2018
• Last Update Posted Date: September 29, 2020
• Actual Study Start Date: October 23, 2014
• Actual Primary Completion Date: September 26, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 18, 2018)

Objective Response Rate (ORR) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: August 1, 2014)

Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]

To assess the efficacy in terms of ORR

Current Secondary Outcome Measures (submitted: May 18, 2018)

• Best Objective Response [ Time Frame: 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.
• Duration of Response- Participants Remaining in Response [ Time Frame: 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.
• Duration of Response [ Time Frame: 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 [ Time Frame: 12 months ]
  Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1
• Disease Control at 6 Months [ Time Frame: 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.
• Progression-free Survival [ Time Frame: 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.
• Overall Survival (OS) [ Time Frame: 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.
• Quality of Life [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: August 1, 2014)

• Duration of response (DoR) [ Time Frame: Up to 2 years ]
  To further assess the efficacy in terms of DoR
• Disease control rate (DCR) [ Time Frame: Up to 2 years ]
  To further assess the efficacy in terms of DCR
• Quality of Life [ Time Frame: Up to 2 years ]
  To explore symptoms and health-related Quality of Life (QoL) using the questionnaires: EORTC QLQ-C30 v3 and the H&N35 module

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: August 1, 2014)

Adverse events (AEs), physical examinations, laboratory findings [ Time Frame: Up to 2 years ]

To assess the safety and tolerability profile

Descriptive Information

• Brief Title: Phase II Study of MEDI4736 Monotherapy in Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
• Official Title: A Phase II, Multi-Center, Single-Arm, Global Study of MEDI4736 Monotherapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Recurrent or Metastatic PD-L1-positive Squamous Cell Carcinoma of the Head and Neck

Intervention

Drug: MEDI4736

MEDI4736 monotherapy

Study Arms

Experimental: MEDI4736

MEDI4736 monotherapy

Intervention: Drug: MEDI4736

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 1, 2014): 112
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 6, 2020
• Actual Primary Completion Date: September 26, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Czechia, France, Georgia, Germany, Hungary, Israel, Korea, Republic of, Malaysia, Spain, Taiwan, United Kingdom, United States
• Removed Location Countries: Australia, Czech Republic

Administrative Information

• NCT Number: NCT02207530
• Other Study ID Numbers: D4193C00001
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

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 request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Supporting Materials: Study Protocol
• Supporting Materials: 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 our timelines, please rerefer to our 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

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: PRA Health Sciences

Investigators

• Principal Investigator: Dan Paul Zandberg, MD; International Coordinating Investigator
• Study Director: Magdalena Wrona; Medical Scientist AstraZeneca Magdalena.Wrona@astrazeneca.com

• PRS Account: AstraZeneca
• Verification Date: September 2020