Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Docetaxel

Osimertinib

Durvalumab

Tremelimumab

Gefitinib

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Gefitinib once daily followed by MEDI4736

Selumetinib twice daily + docetaxel, followed by MEDI4736

Tremelimumab every 4 weeks followed by MEDI4736

AZD9291

Selumetinib+Docetaxel

Samir N. Khleif, MD

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.

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)

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.

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.

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.

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.

To assess the efficacy of various sequences. In survival follow up at data cut off.

Quintiles, Inc.

AstraZeneca

Gefitinib once daily followed by MEDI4736 - analyses not done due to low n

Gefitinib With a Seq. Switch to a MEDI4736

Selumetinib twice daily + docetaxel, followed by MEDI4736 - analyses not done due to low n

Selumetinib+Docetaxel With a Seq. Switch to a MEDI4736

The 1 patient in the AZD9291 cohort was not dosed and no data were recorded in the database.

AZD9291 With a Seq. Switch to MEDI4736

Tremelimumab every 4 weeks (1 cycle) followed by MEDI4736

Tremelimumab (1 Cycle) With a Seq. Switch to a MEDI4736

TREMELIMUMAB 10MG/KG Q4W 8WEEKS/MEDI4736 10MG/KG Q2W 12MONTHS

Tremelimumab (2 Cycles) With a Seq. Switch to MEDI4736

The 1 patient in the AZD9291 cohort was not dosed and no baseline data were recorded in the database.

AZD9291 With a Seq. Switch to a MEDI4736

Total

Age, Continuous

Sex: Female, Male

White

Black or African American

Race/Ethnicity, Customized

The 1 patient in the AZD9291 cohort was not dosed and no baseline data were recorded in the database. Because the AZD9291 with a Seq. Switch to a MEDI4736 arm had no data recorded during the study, this arm is not included in the reporting of adverse events.

Phillip Dennis

Tremelimumab every 4 weeks (2 cycles) followed by MEDI4736

Per the analysis plan, efficacy would not be analyzed for treatment groups that did not have a sufficient number of enrolled patients.

Confirmed Complete Response (CR) Rate

Objective Response Rate (ORR)

Progression-free Survival

Per the analysis plan, efficacy would not be analyzed for treatment groups that did not have a sufficient number of enrolled patients. Response was observed for 1 patient in the Tremelimumab 1-cycle arm for up to and including 6 months.

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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