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

NCT02088112 | Completed Phase 1

• 1 other identifier: D791PC00001
• Study Type: interventional
• Target: 56
• Locations: 3 countries
• Sites: 7

Brief Summary

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

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

NSCLC

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  From first dose of study treatment until 90 days after the last dose, assessed up to 32 months

Secondary Outcomes (5)

• To obtain a preliminary assessment of the anti-tumour activity of gefitinib in combination with MEDI4736 by evaluation of tumour response

  From baseline assessment to disease progression, assessed up to 30 months

• To determine the immunogenicity of MEDI4736 in combination with gefitinib: anti-drug antibodies (ADAs)

  From first dose of study treatment until 90 days after the last dose, assessed up to 32 months

• To determine the pharmacokinetics of MEDI4736

  From first dose of study treatment until 90 days after the last dose, assessed up to 32 months

• To assess MEDI4736 pharmacodynamics in subjects receiving MEDI4736 in combination with gefitinib.

  From first dose of study treatment until 90 days after the last dose, assessed up to 32 months

• To determine overall survival (OS) in expansion Arm 1 and Arm 1a patients

  From final safety follow-up visit after last dose until 1 year after the final patient discontinues investigational product (initial Medi4736).

Study Arms (2)

Escalation

EXPERIMENTAL

MEDI4736 will be combined with gefitinib to assess safety and tolerability

Drug: Gefitinib; Drug: MEDI4736

Expansion Arm

EXPERIMENTAL

MEDI4736 will be combined with gefitinib

Drug: Gefitinib; Drug: MEDI4736

Interventions

Gefitinib DRUG

Gefitinib QD

Escalation; Expansion Arm

MEDI4736 DRUG

MEDI4736 IV Q2W

Escalation; Expansion Arm

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated, written informed consent
• Male or female aged 18 years and older.
• 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
• a.For Escalation Phase: At least one lesion (measurable and/or non-measurable) b.For Expansion Phase: At least one measurable lesion.
• 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

You may not qualify if:

• Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment.
• Any investigational agent, chemotherapy, immunotherapy, biologic, hormonal within 28 days of the first dose of study treatment
• Inadequate bone marrow reserve or organ function

Sponsors & Collaborators

• MedImmune LLC: lead
• AstraZeneca: collaborator

Study Sites (7)

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Seattle, Washington, 98109, United States

Location

Research Site

Chūōku, 104-0045, Japan

Location

Research Site

Matsuyama, 791-0280, Japan

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Related Publications (1)

• Creelan BC, Yeh TC, Kim SW, Nogami N, Kim DW, Chow LQM, Kanda S, Taylor R, Tang W, Tang M, Angell HK, Roudier MP, Marotti M, Gibbons DL. A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer. Br J Cancer. 2021 Jan;124(2):383-390. doi: 10.1038/s41416-020-01099-7. Epub 2020 Oct 5.

  PMID: 33012782 DERIVED

Related Links

• Related Info
• Results of this clinical trial are available on www.astrazenecaclinicaltrials.com

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Gefitinib; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2014
• First Posted: March 14, 2014
• Study Start: March 24, 2014
• Primary Completion: March 9, 2021
• Study Completion: March 9, 2021
• Last Updated: April 4, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (3); KR (2); JP (2)