Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

A Phase IIa, Open-Label, Multi-Center, Multi-Cohort, Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)

Primary objective: To assess the efficacy of various sequences of either a small molecule or an IMT (IMT-A) followed by a IMT-B (MEDI4736) .

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)
• Intervention / Treatment: Drug: Gefitinib; Drug: AZD9291; Drug: Selumetinib+Docetaxel; Drug: Tremelimumab

Detailed Description

This is a multi-arm, multi-cohort, Phase IIa, open-label study of selected small molecules (gefitinib, AZD9291, or selumetinib + docetaxel) or 1st IMT (hereafter referred to as IMT-A; tremelimumab) followed by sequential switch to a 2nd IMT (hereafter referred to as IMT-B; MEDI4736) in locally advanced or metastatic NSCLC (Stage IIIB-IV). Patients will be enrolled concurrently into multiple cohorts.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Research Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Research Site
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Research Site
    • Marietta, Georgia, United States, 30060
      • Research Site
  • Kentucky
    • Ashland, Kentucky, United States, 41101
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New York
    • Mineola, New York, United States, 11501
      • Research Site
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Research Site
  • Washington
    • Spokane, Washington, United States, 99208-1129
      • Research Site
    • Tacoma, Washington, United States, 98405
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of archived tumor tissue sample and mandatory tissue biopsy
• Patients must have either histologically or cytologically documented NSCLC who present with locally advanced or metastatic stage IIIB-IV disease
• Life expectancy ≥12 weeks
• Patients must have measurable disease and at least 1 lesion not previously irradiated
• World Health Organization (WHO) performance status of 0 or 1

Exclusion Criteria:

• Mixed small cell and NSCLC histology
• Prior exposure to any anti-PD-1 or anti-PD-L1 antibody

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gefitinib with a Seq. Switch to a MEDI4736; Gefitinib once daily followed by MEDI4736	Drug: Gefitinib; Gefitinib once daily followed by MEDI4736
Experimental: AZD9291 with a Seq. Switch to a MEDI4736; AZD9291 once daily followed by MEDI4736	Drug: AZD9291; AZD9291 once daily followed by MEDI4736
Experimental: Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736; Selumetinib twice daily + docetaxel, followed by MEDI4736	Drug: Selumetinib+Docetaxel; Selumetinib twice daily + docetaxel, followed by MEDI4736
Experimental: Tremelimumab with a Seq. Switch to a MEDI4736; Tremelimumab every 4 weeks followed by MEDI4736	Drug: Tremelimumab; Tremelimumab every 4 weeks followed by MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Complete Response (CR) Rate	To assess the efficacy of various sequences. CR (per RECIST 1.1 as assessed by the local/site Investigator) is defined as the disappearance of all target and non-target lesions. Confirmed complete response rate (CR rate) is defined as the number (%) of patients with a confirmed overall response of CR and was based on the evaluable analysis set.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	To further assess the efficacy of various sequences. Objective response rate (ORR; per RECIST 1.1 as assessed by the site Investigator) is defined as the number (%) of patients with a confirmed overall response of CR or PR and was based on the evaluable analysis set. Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 2 years
Progression-free Survival	Progression-free survival (per RECIST 1.1 as assessed by Investigator) is defined as the date of 1st dose of MEDI4736 until the date of objective disease progression or death. Progression of disease (PD) At least a 20% increase in the sum of diameters of TLs, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Up to 2 years
Duration of Response	Duration of response (DoR; per RECIST 1.1 as assessed by the site Investigator) will be defined as the time from the date of 1st documented response (which is subsequently confirmed) until the 1st date of documented progression or death in the absence of disease progression.	Within 12 months
Overall Survival	To assess the efficacy of various sequences. In survival follow up at data cut off.	Up to 2 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Quintiles, Inc.
• Investigators: Principal Investigator: Samir N. Khleif, MD, International Coordinating Investigator

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2014
• Primary Completion (Actual): June 11, 2016
• Study Completion (Actual): June 11, 2016

Study Registration Dates

• First Submitted: June 30, 2014
• First Submitted That Met QC Criteria: June 30, 2014
• First Posted (Estimate): July 2, 2014

Study Record Updates

• Last Update Posted (Actual): August 2, 2019
• Last Update Submitted That Met QC Criteria: August 1, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Lung cancer; NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protein Kinase Inhibitors; Docetaxel; Gefitinib; Tremelimumab; Osimertinib
• Other Study ID Numbers: D4191C00011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No