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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02088112
• Other study ID #: D791PC00001
• Status: Completed
• Phase: Phase 1
• Start date: March 24, 2014
• Est. completion date: March 9, 2021

Study information

• Verified date: March 2022
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

In Escalation phase: MEDI4736 and gefitinib in NSCLC subjects In Expansion phase: Subjects with EGFR mutation positive locally advanced or metastatic NSCLC will be enrolled in expansion arms. Initiation of expansion arms with the recommended dose of MEDI4736 in combination with gefitinib will be based on an adequate safety and tolerability profile of the combination from the escalation phase.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: March 9, 2021
• Est. primary completion date: March 9, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Key Inclusion Criteria:

1. Provision of signed and dated, written informed consent

2. Male or female aged 18 years and older.

3. 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

4. a.For Escalation Phase: At least one lesion (measurable and/or non-measurable) b.For Expansion Phase: At least one measurable lesion.

5. 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

Key Exclusion Criteria:

1. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment.

2. Any investigational agent, chemotherapy, immunotherapy, biologic, hormonal within 28 days of the first dose of study treatment

3. Inadequate bone marrow reserve or organ function

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Gefitinib
Gefitinib QD
• MEDI4736
MEDI4736 IV Q2W

Locations

Country	Name	City	State
Japan	Research Site	Chuo-ku
Japan	Research Site	Matsuyama-shi
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
United States	Research Site	Houston	Texas
United States	Research Site	Seattle	Washington
United States	Research Site	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
MedImmune LLC	AstraZeneca

Countries where clinical trial is conducted

United States,  Japan,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	To obtain a preliminary assessment of the anti-tumour activity of gefitinib in combination with MEDI4736 by evaluation of tumour response	At each visit subjects will be programmatically assigned a RECIST visit response of CR, PR, SD or PD depending on the status of their disease compared to baseline and previous assessments; Objective response rate: the percentage of subjects who have at least one visit response of CR or PR prior to any evidence of progression . Disease control rate: the percentage of subjects who have at least one visit response of CR or PR or SD prior to any evidence of progression. Progression Free Survival (PFS) : the time from start of study treatment to the first documentation of objective disease progression (PD) or death from any cause.	From baseline assessment to disease progression, assessed up to 30 months
Secondary	To determine the immunogenicity of MEDI4736 in combination with gefitinib: anti-drug antibodies (ADAs)	Assessed by evaluating the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs). The impact of ADAs on overall MEDI4736 PK will also be evaluated.	From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
Secondary	To determine the pharmacokinetics of MEDI4736	Individual MEDI4736 concentrations will be tabulated by dose cohort along with descriptive statistics. Noncompartmental PK data analysis will be performed	From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
Secondary	To assess MEDI4736 pharmacodynamics in subjects receiving MEDI4736 in combination with gefitinib.	PD-L1 levels before and after treatment with MEDI4736 will be measured to evaluate its association with response to treatment with MEDI4736 and clinical outcome	From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
Secondary	To determine overall survival (OS) in expansion Arm 1 and Arm 1a patients	Survival information may be obtained via telephone contact with the patient, patients family or by checking the patients notes, hospital records, contacting the patients general practitioner or public death registry, where it is possible to do so under applicable local laws.	From final safety follow-up visit after last dose until 1 year after the final patient discontinues investigational product (initial Medi4736).

External Links

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