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MEDI4736 (Anti PD-L1) Combined With Gefitinib in Subjects With Non-Small Cell Lung Cancer(NSCLC)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT02088112
First received: March 7, 2014
Last updated: May 25, 2017
Last verified: May 2017
  Purpose
This a Phase I, Open-Label, Multicentre Study to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumour activity of gefitinib in combination with MEDI4736 (anti PD-L1) in Subjects with Non-small cell lung cancer (NSCLC). The study consists of two phases: Escalation phase and an expansion phase to be conducted in locally advanced or metastatic NSCLC subjects

Condition Intervention Phase
Patients With Non-Small Cell Lung Cancer(NSCLC) Drug: Gefitinib Drug: MEDI4736 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Gefitinib in Combination With MEDI4736 (Anti PD-L1) in Subjects With Non-Small Cell Lung Cancer(NSCLC)

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Escalation Phase: safety and tolerability: AEs, laboratory data, vital signs, ECG changes and Echo. Expansion Phase: safety and tolerability of the recommended dose for MEDI4736; AEs, laboratory data, vital signs, ECG changes and Echo. [ Time Frame: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months ]
    AEs: Type, incidence, severity, seriousness and relationship to study medications of adverse events (AE) (graded by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE]; Safety Labs: Blood and urine samples for determination of clinical chemistry, hematology, coagulation, thyroid function tests and urinalysis will be taken at the visits; any laboratory abnormalities, and including dose-limiting toxicities (DLTs), ECG measurements and Creatinine Clearance


Secondary Outcome Measures:
  • To obtain a preliminary assessment of the anti-tumour activity of gefitinib in combination with MEDI4736 by evaluation of tumour response [ Time Frame: From baseline assessment to disease progression, assessed up to 30 months ]
    At each visit subjects will be programmatically assigned a RECIST visit response of CR, PR, SD or PD depending on the status of their disease compared to baseline and previous assessments; Objective response rate: the percentage of subjects who have at least one visit response of CR or PR prior to any evidence of progression . Disease control rate: the percentage of subjects who have at least one visit response of CR or PR or SD prior to any evidence of progression. Progression Free Survival (PFS) : the time from start of study treatment to the first documentation of objective disease progression (PD) or death from any cause.

  • To determine the immunogenicity of MEDI4736 in combination with gefitinib: anti-drug antibodies (ADAs) [ Time Frame: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months ]
    Assessed by evaluating the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs). The impact of ADAs on overall MEDI4736 PK will also be evaluated.

  • To determine the pharmacokinetics of MEDI4736 [ Time Frame: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months ]
    Individual MEDI4736 concentrations will be tabulated by dose cohort along with descriptive statistics. Noncompartmental PK data analysis will be performed

  • To assess MEDI4736 pharmacodynamics in subjects receiving MEDI4736 in combination with gefitinib. [ Time Frame: From first dose of study treatment until 90 days after the last dose, assessed up to 32 months ]
    PD-L1 levels before and after treatment with MEDI4736 will be measured to evaluate its association with response to treatment with MEDI4736 and clinical outcome

  • To determine overall survival (OS) in expansion Arm 1 and Arm 1a patients [ Time Frame: From final safety follow-up visit after last dose until 36 months after Last Subject enrolled ]
    Survival information may be obtained via telephone contact with the patient, patients family or by checking the patients notes, hospital records, contacting the patients general practitioner or public death registry, where it is possible to do so under applicable local laws.


Enrollment: 56
Actual Study Start Date: March 24, 2014
Estimated Study Completion Date: June 14, 2019
Estimated Primary Completion Date: June 14, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Escalation
MEDI4736 will be combined with gefitinib to assess safety and tolerability
Drug: Gefitinib
Gefitinib QD
Drug: MEDI4736
MEDI4736 IV Q2W
Experimental: Expansion Arm
MEDI4736 will be combined with gefitinib
Drug: Gefitinib
Gefitinib QD
Drug: MEDI4736
MEDI4736 IV Q2W

Detailed Description:
In Escalation phase: MEDI4736 and gefitinib in NSCLC subjects In Expansion phase: Subjects with EGFR mutation positive locally advanced or metastatic NSCLC will be enrolled in expansion arms. Initiation of expansion arms with the recommended dose of MEDI4736 in combination with gefitinib will be based on an adequate safety and tolerability profile of the combination from the escalation phase.
  Eligibility

Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Provision of signed and dated, written informed consent
  2. Male or female aged 18 years and older.
  3. Subjects must have a. In the escalation phase, locally advanced or metastatic NSCLC subjects who have either failed to respond or relapsed following any line of standard treatment, were unable to tolerate, or were not eligible for standard treatment b. In the expansion phase, histologically or cytologically confirmed locally advanced or metastatic NSCLC that is EGFR mutation positive, naïve to EGFR TKI therapy, and sensitive to EGFR TKIs therapy
  4. a.For Escalation Phase: At least one lesion (measurable and/or non-measurable) b.For Expansion Phase: At least one measurable lesion.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

    • For Japan Escalation - the same as the global escalation I/E criteria except patients must be EGFR mutation positive

Key Exclusion Criteria:

  1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment.
  2. Any investigational agent, chemotherapy, immunotherapy, biologic, hormonal within 28 days of the first dose of study treatment
  3. Inadequate bone marrow reserve or organ function
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02088112

Locations
United States, Florida
Research Site
Tampa, Florida, United States, 33612
United States, Texas
Research Site
Houston, Texas, United States, 77030
United States, Washington
Research Site
Seattle, Washington, United States, 98109
Japan
Research Site
Chuo-ku, Japan, 104-0045
Research Site
Matsuyama-shi, Japan, 791-0280
Korea, Republic of
Research Site
Seoul, Korea, Republic of, 05505
Research Site
Seoul, Korea, Republic of, 110-744
Sponsors and Collaborators
MedImmune LLC
AstraZeneca
Investigators
Principal Investigator: Ben Creelan, MD Moffit Cancer Center
Principal Investigator: Don Gibbons, MD M.D. Anderson Cancer Center
Principal Investigator: Laura Chow, MD University of Washington
Principal Investigator: Sang-We Kim, MD Asan Medical Center
Principal Investigator: Dong-Wan Kim, MD Seoul National University Hospital
Principal Investigator: Shinitaro Kanda, MD National Cancer Center
Principal Investigator: Naoyuki Nogami Shikoku Cancer Center
  More Information

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT02088112     History of Changes
Other Study ID Numbers: D791PC00001
Study First Received: March 7, 2014
Last Updated: May 25, 2017

Keywords provided by MedImmune LLC:
NSCLC

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antibodies, Monoclonal
Gefitinib
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 23, 2017