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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Escalation | Experimental | MEDI4736 will be combined with gefitinib to assess safety and tolerability |
|
| Expansion Arm | Experimental | MEDI4736 will be combined with gefitinib |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gefitinib | Drug | Gefitinib QD |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Key Inclusion Criteria:
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.
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Tampa | Florida | 33612 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33012782 | Derived | 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. |
| Label | URL |
|---|---|
| Related Info | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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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.
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.
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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| ID | Term |
|---|---|
| D000077156 | Gefitinib |
| C000613593 | durvalumab |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| MEDI4736 |
| Drug |
MEDI4736 IV Q2W |
|
| 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) | 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 |
| 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 |
| 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 |
| 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). |
| Houston |
| Texas |
| 77030 |
| United States |
| Research Site | Seattle | Washington | 98109 | United States |
| Research Site | Chūōku | 104-0045 | Japan |
| Research Site | Matsuyama | 791-0280 | Japan |
| Research Site | Seoul | 03080 | South Korea |
| Research Site | Seoul | 05505 | South Korea |
| Results of this clinical trial are available on www.astrazenecaclinicaltrials.com | View source |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |