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

AstraZeneca

Status and phase: Completed; Phase 2

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

Treatments: Drug: Selumetinib+Docetaxel; Drug: Gefitinib; Drug: Tremelimumab; Drug: AZD9291

Study type: Interventional

Funder types: Industry

Identifiers

NCT02179671

D4191C00011

Details and patient eligibility

About

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) .

Full 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.

Enrollment: 32 patients

Sex: All

Ages: 18 to 130 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

32 participants in 4 patient groups

Gefitinib with a Seq. Switch to a MEDI4736

Experimental group

Description:

Gefitinib once daily followed by MEDI4736

Treatment:

Drug: Gefitinib

AZD9291 with a Seq. Switch to a MEDI4736

Experimental group

Description:

AZD9291 once daily followed by MEDI4736

Treatment:

Drug: AZD9291

Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736

Experimental group

Description:

Selumetinib twice daily + docetaxel, followed by MEDI4736

Treatment:

Drug: Selumetinib+Docetaxel

Tremelimumab with a Seq. Switch to a MEDI4736

Experimental group

Description:

Tremelimumab every 4 weeks followed by MEDI4736

Treatment:

Drug: Tremelimumab