Clinical Trials /

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

NCT02088112

Description:

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

Related Conditions:
  • Lung Carcinoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02088112

Trial Eligibility

Document

Title

  • Brief Title: MEDI4736 (Anti PD-L1) Combined With Gefitinib in Subjects With Non-Small Cell Lung Cancer(NSCLC).
  • 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 IDs

  • ORG STUDY ID: D791PC00001
  • NCT ID: NCT02088112

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
GefitinibEscalation
MEDI4736Escalation

Purpose

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

Detailed 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.

Trial Arms

NameTypeDescriptionInterventions
EscalationExperimentalMEDI4736 will be combined with gefitinib to assess safety and tolerability
  • Gefitinib
  • MEDI4736
Expansion ArmExperimentalMEDI4736 will be combined with gefitinib
  • Gefitinib
  • MEDI4736

Eligibility Criteria

        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
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Time Frame:From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:To obtain a preliminary assessment of the anti-tumour activity of gefitinib in combination with MEDI4736 by evaluation of tumour response
Time Frame:From baseline assessment to disease progression, assessed up to 30 months
Safety Issue:
Description: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.
Measure:To determine the immunogenicity of MEDI4736 in combination with gefitinib: anti-drug antibodies (ADAs)
Time Frame:From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
Safety Issue:
Description: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.
Measure:To determine the pharmacokinetics of MEDI4736
Time Frame:From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
Safety Issue:
Description:Individual MEDI4736 concentrations will be tabulated by dose cohort along with descriptive statistics. Noncompartmental PK data analysis will be performed
Measure:To assess MEDI4736 pharmacodynamics in subjects receiving MEDI4736 in combination with gefitinib.
Time Frame:From first dose of study treatment until 90 days after the last dose, assessed up to 32 months
Safety Issue:
Description: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
Measure:To determine overall survival (OS) in expansion Arm 1 and Arm 1a patients
Time Frame:From final safety follow-up visit after last dose until 1 year after the final patient discontinues investigational product (initial Medi4736).
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:MedImmune LLC

Trial Keywords

  • NSCLC

Last Updated

April 13, 2021