Carcinoma, Non-Small-Cell LungPhase 1NCT02088112
MEDI4736 (Anti PD-L1) Combined With Gefitinib in Subjects With Non-Small Cell Lung Cancer(NSCLC).
A Phase 1 study testing Gefitinib and MEDI4736 in people with Carcinoma, Non-Small-Cell Lung, run by MedImmune LLC at 7 sites in 3 countries.
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). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Gefitinib and MEDI4736
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 24 Mar 2014to 9 Mar 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
United States3 sites
Research Site
Houston, Texas, 77030
Research Site
Seattle, Washington, 98109
Research Site
Tampa, Florida, 33612
About this study
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)
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
Read the 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.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Gefitinib, MEDI4736
- Keywords
- NSCLC
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GefitinibDrug
Gefitinib QD
MEDI4736Drug
MEDI4736 IV Q2W
| Study group | Role | What they receive |
|---|---|---|
| Escalation | Experimental | MEDI4736 will be combined with gefitinib to assess safety and tolerability Receives: Drug: Gefitinib; Drug: MEDI4736 |
| Expansion Arm | Experimental | MEDI4736 will be combined with gefitinib Receives: Drug: Gefitinib; Drug: MEDI4736 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: From final safety follow-up visit after last dose until 1 year after the final patient discontinues investigational product (initial Medi4736).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2014 (estimated)
- Study start24 Mar 2014
- Primary completion9 Mar 2021
- Study completion9 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Responsible party
- Sponsor
- Investigators
- Ben Creelan, MD, Principal investigator, Moffit Cancer CenterDon Gibbons, MD, Principal investigator, M.D. Anderson Cancer CenterLaura Chow, MD, Principal investigator, University of WashingtonSang-We Kim, MD, Principal investigator, Asan Medical CenterDong-Wan Kim, MD, Principal investigator, Seoul National University HospitalShinitaro Kanda, MD, Principal investigator, National Cancer CenterNaoyuki Nogami, Principal investigator, Shikoku Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02088112
- Sponsor's protocol ID
- D791PC00001
- Status last verified
- Mar 2022
- First submitted
- 7 Mar 2014
- Last updated
- 4 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 33012782
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02088112
- Acronym / sponsor ID
- D791PC00001
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- NSCLC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Collaborators
- AstraZeneca
- Study start
- 24 Mar 2014 (actual)
- Primary completion
- 9 Mar 2021 (actual)
- Study completion
- 9 Mar 2021 (actual)
- First posted
- 14 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Escalation | Experimental | Drug: Gefitinib, Drug: MEDI4736MEDI4736 will be combined with gefitinib to assess safety and tolerability |
| Expansion Arm | Experimental | Drug: Gefitinib, Drug: MEDI4736MEDI4736 will be combined with gefitinib |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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 (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GefitinibGefitinib QD | Drug | Escalation, Expansion Arm |
| MEDI4736MEDI4736 IV Q2W | Drug | Escalation, Expansion Arm |
Primary outcome
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
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
5 secondary outcomes
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
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
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
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
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2022.
- Derived from this study: PubMed 33012782Creelan 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.
- Related InfoLink provided by the sponsor.
- Results of this clinical trial are available on www.astrazenecaclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ben Creelan, MD principal investigator
Moffit Cancer Center
Don Gibbons, MD principal investigator
M.D. Anderson Cancer Center
Laura Chow, MD principal investigator
University of Washington
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gefitinib and MEDI4736 in people with Carcinoma, Non-Small-Cell Lung, run by MedImmune LLC at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Japan, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02088112, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2022.