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

AstraZeneca32 enrolled

Overview

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) .

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Stage IIIB-IV)

Interventions

GefitinibDRUG

Gefitinib once daily followed by MEDI4736

AZD9291DRUG

AZD9291 once daily followed by MEDI4736

Selumetinib+DocetaxelDRUG

Selumetinib twice daily + docetaxel, followed by MEDI4736

Eligibility

Sex: ALLMin age: 18 YearsMax age: 130 Years

Medical Language ↔ Plain English

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

Locations (10)

Research Site

Goodyear, Arizona, United States

Research Site

Washington D.C., District of Columbia, United States

Research Site

Augusta, Georgia, United States

Research Site

Marietta, Georgia, United States

Outcomes

Primary Outcomes

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.

Time frame: Up to 2 years

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Within 12 months

Data from ClinicalTrials.gov

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