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EGFR Mutant Advanced Non Small Cell Lung CancerPhase 2ILLUMINATENCT03994393

Non Small Cell Lung Cancer Trial of Durvalumab and Tremelimumab in Advanced Epidermal Growth Factor Receptor (EGFR) Mutant Disease.

A Phase 2 study testing Tremelimumab and Durvalumab in people with EGFR Mutant Advanced Non Small Cell Lung Cancer, run by University of Sydney at 16 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

The primary purpose of this trial is to evaluate the efficacy and tolerability of durvalumab and tremelimumab with platinum-pemetrexed in patients with metastatic NSCLC (T790+ve or T790M-ve) following progression on EGFR Tyrosine Kinase Inhibitors.. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tremelimumab and Durvalumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
16 sitesin 2 countries
Study dates
23 Oct 2018to 31 Jan 2024
Phase
Phase 2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults, aged 18 years and older with histologically and/or cytologically confirmed non-squamous non-small cell lung cancer with EGFR mutation of Exon 19 deletion or Exon 21 L858R point mutation.
  • Patients with co-mutations are allowed as long as one of the mutation is either Exon 19 deletion or Exon 21 L858R point mutation
  • Patients with mixed histology must have non-squamous NSCLC as the predominant histology.
  • Disease that has progressed and either:
  • No evidence of EGFR T790M resistance mutation in both tissue re-biopsy and plasma after one-line of EGFR tyrosine kinase inhibitor therapy (TKI) OR (ii) T790M mutation (detected in tissue re-biopsy, plasma or both) and progression on 3rd generation EGFR TKI; patients are allowed to have one prior line of TKI therapy before 3rd generation TKI
  • Measurable disease according to RECIST 1.1
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  • ECOG performance status of 0 or 1
  • Adequate bone marrow function as defined below (within 14 days prior to registration and with values within the ranges specified below):
  • Platelets equal to or greater than 100 x 109/L
  • Absolute neutrophil count (ANC) equal to or greater than 1.0 x 109/L (equal to or greater than 1000 per mm3)
  • Haemoglobin equal to or greater than 90 x g/L
  • Adequate liver function (within 14 days prior to registration and with values within the ranges specified below):
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) equal to or less than 2.5 x institutional upper limit of normal (ULN). (or equal to or less than 5 x ULN if liver metastases are present)
  • Bilirubin equal to or less than 1.5 x ULN
  • Adequate renal function (within 14 days prior to registration):
  • Measured creatinine clearance greater than 40 mL/min or Calculated creatinine clearance greater than 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
  • Provision of a pre-treatment tumour tissue sample from a biopsy taken within 42 days prior to enrolment (core biopsy preferred) to determine NSCLC histology and for translational research.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.
  • Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Signed written informed consent (main study and optional biobanking).

Who cannot join

  • Prior chemotherapy or immunotherapy, including prior anti-PD-1/anti-PD-L1 or anti-CTLA-4 antibodies, for advanced NSCLC.
  • For recurrent, incurable disease, prior adjuvant chemotherapy or concurrent chemotherapy and radiotherapy with curative intent is allowed, but must have been completed more than 6 months ago, and must not have included treatment with an immune checkpoint inhibitor.
  • Prior EGFR-TKI (e.g. erlotinib, gefitinib, afatinib or osimertinib), including experimental TKI agents, within 8 days or approximately 5 x half-life, whichever is the longer, of the first dose of study treatment is allowed. (If sufficient washout time has not occurred due to schedule or PK properties, an alternative appropriate washout time based on known duration and time to reversibility of drug related adverse events could be agreed upon by contacting the ILLUMINATE Study Team).
  • Mixed histology with any small cell or squamous component.
  • Life expectancy of less than 3 months.
  • Current enrolment or participation in another clinical study with an investigational product during the last 12 months, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study must first be discussed with ILLUMINATE Study Team before study enrolment.
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  • Any unresolved toxicity NCI CTCAE equal to or greater than Grade 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
  • Patients with equal to or greater than Grade 2 neuropathy will be evaluated on a case-by-case basis after consultation with the ILLUMINATE Study Team.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the ILLUMINATE Study Team.
  • Radiotherapy or major surgery (as defined by the local investigator) within 4 weeks of the first dose of study drug. Note: Local surgery on isolated lesions for palliative intent is acceptable.
  • History of pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function.
  • History of active primary immunodeficiency or allogeneic transplant.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis (with the exception of diverticulosis), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety.
  • History of another primary malignancy except for
  • Malignancy treated with curative intent and with no known active disease equal to or greater than 5 years before the first dose of IP and of low potential risk for recurrence
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma insitu without evidence of disease.
  • Any history of leptomeningeal carcinomatosis, or untreated central nervous system metastases obtained during the screening period or identified prior to signing the PICF. Patients whose brain metastases have been treated may participate provided they show radiographic stability (defined as disease stability on imaging 4 weeks after commencing radiotherapy). Any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of equal to or less than 10mg/day of prednisone or its equivalent (and anti-epileptic drugs) for at least 14 days prior to the start of treatment.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
  • Live attenuated vaccine within 30 days prior to the first dose of study drug, whilst receiving study drug and up to 30 days after the last dose of study drug.
  • Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
  • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab plus tremelimumab combination therapy.
  • Known allergy or hypersensitivity to any of the study drugs or excipients.

Trial locations and contacts

16 sites in 2 countries.

16 sites in 2 countries

Australia9 sites

  • Flinders Medical Centre

    Bedford Park, South Australia

  • The Prince Charles Hospital

    Chermside, Queensland

  • Monash Medical Centre - Clayton

    Clayton, Victoria

  • Royal Hobart Hospital

    Hobart, Tasmania

  • St George Hospital

    Kogarah, New South Wales

  • Liverpool Hospital

    Liverpool, New South Wales

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria

  • St Vincent's Hospital (Melbourne)

    Melbourne, Victoria

  • Princess Alexandra Hospital

    Woolloongabba, Queensland

Other trials in Australia

Taiwan7 sites

  • Taiwan Dalin Tzu Chi Hospital

    Chiayi City

  • Taiwan China Medical University Hospital

    Taichung

  • Taiwan Taichung Veterans General Hospital

    Taichung

  • Taiwan National Cheng Kung University Hospital

    Tainan

  • National Taiwan University Hospital

    Taipei

  • Taiwan Taipei Veterans General Hospital

    Taipei

  • Taiwan Tri-Service General Hospital

    Taipei

Other trials in Taiwan

About this study

Official title: A Phase 2 Trial of Durvalumab (MEDI4736) and Tremelimumab With Chemotherapy in Metastatic EGFR Mutant Non-squamous Non-small Cell Lung Cancer (NSCLC) Following Progression on EGFR Tyrosine Kinase Inhibitors (TKIs)

The primary purpose of this trial is to evaluate the efficacy and tolerability of durvalumab and tremelimumab with platinum-pemetrexed in patients with metastatic NSCLC (T790+ve or T790M-ve) following progression on EGFR Tyrosine Kinase Inhibitors..

Study population:

Read more

Individuals may be eligible to enrol in this trial if aged 18 or over and have been diagnosed with advanced non-small cell lung cancer (T790+ve or T790M-ve) following progression on EGFR Tyrosine Kinase Inhibitors.

Study details:

All participants enrolled in this trial will begin with induction therapy which involves 4 cycles of durvalumab 1500mg and tremelimumab 75mg with cisplatin 75mg/m2 or carboplatin AUC 5, and pemetrexed 500mg/m2 intravenously every 3 weeks.

Participants will then move into a maintenance phase of durvalumab 1500mg and pemetrexed 500mg/m2 once every 4 weeks until disease progression or unacceptable side effects.

All patients will be reviewed every three to four weeks by blood samples, CT scans and side effect assessments.

It is hoped that the findings from this trial will provide information on whether treatment with durvalumab and tremelimumab with platinum-pemetrexed is feasible, safe and effective for the treatment of advanced non-small cell lung cancer (T790+ve or T790M-ve).

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TremelimumabDrug

    During induction, patients will receive 4 cycles of durvalumab 1500mg and tremelimumab 75mg with cisplatin 75mg/m2 (or carboplatin AUC 5 if cisplatin is contra-indicated), and pemetrexed 500mg/m2 via intravenous infusion every 3 weeks.

    Followed immediately by a maintenance phase of durvalumab 1500mg and pemetrexed 500mg/m2 once every 4 weeks via intravenous infusion until disease progression or intolerance.

  • DurvalumabDrug

    During induction, patients will receive 4 cycles of durvalumab 1500mg and tremelimumab 75mg with cisplatin 75mg/m2 (or carboplatin AUC 5 if cisplatin is contra-indicated), and pemetrexed 500mg/m2 via intravenous infusion every 3 weeks.

    Followed immediately by a maintenance phase of durvalumab 1500mg and pemetrexed 500mg/m2 once every 4 weeks via intravenous infusion until disease progression or intolerance.

Study groups in NCT03994393
Study groupRoleWhat they receive
Cohort 1Active comparatorParticipants with no evidence of T790M
Receives: Drug: Tremelimumab; Drug: Durvalumab
Cohort 2Active comparatorParticipants with evidence of T790M
Receives: Drug: Tremelimumab; Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective tumour response rate (OTRR) and Objective tumour response (OTR)

    Objective tumour response rate (OTRR) as defined by RECIST 1.1. Objective tumour response (OTR) is defined as a partial response or compete response by RECIST 1.1. OTRR is defined as the proportion (percentage) of participants with a confirmed CR or PR according to RECIST 1.1.

    Measured: 36 months post enrolment of first participant.

Secondary outcomes (6)

  1. Disease control (Disease Control Rate (DCR)

    Disease control (Disease Control Rate (DCR) = Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) as defined by RECIST 1.1.

    Measured: 36 months post enrolment of first participant.

  2. Objective tumour response rate (OTRR) & Objective tumour response (OTR)

    Objective tumour response rate (OTRR) as defined by iRECIST. Objective tumour response (OTR) is defined as a partial response or compete response by iRECIST. OTRR is defined as the proportion (percentage) of participants with a confirmed CR or PR according to iRECIST.

    Measured: 36 months post enrolment of first participant.

  3. Progression-free survival (PFS)

    Progression-free survival (PFS) as defined by RECIST 1.1 and iRECIST. PFS is defined as the interval from date of registration to the date of first evidence of disease progression or death, whichever occurs first. Disease progression is defined according to RECIST 1.1 and iRECIST.

    Measured: 36 months post enrolment of first participant.

  4. Progression-free survival at 12 months (PFS12)

    Progression-free survival at 12 months (PFS12) as defined by RECIST 1.1 and iRECIST. PFS at 12 months taken to mean 1 calendar year, i.e. 365 days. Study participants who have stable disease, partial response or complete response confirmed at the first scheduled assessment after 12 months according to RECIST v1.1 will be considered to have attained PFS at 12 months.

    Measured: 12 months post enrolment of last participant.

  5. Overall survival (OS)

    Overall survival (OS) is defined as the interval from the date of registration to date of death from any cause, or the date of last known follow-up alive.

    Measured: 36 months from enrolment of first participant.

  6. Number and Severity (assessed as a composite) of Adverse Events

    Number and Severity (assessed as a composite) of Adverse Events - using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

    Measured: 36 months post enrolment of first participant.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jun 2019
  2. Study start23 Oct 2018
  3. Primary completion30 Jun 2023 (estimated)
  4. Study completion31 Jan 2024 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03994393
Sponsor's protocol ID
CTC 0209
Other IDs
ALTG 16/009
Acronym
ILLUMINATE
Status last verified
Apr 2023
First submitted
20 Jun 2019
Last updated
21 Apr 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lee CK, Liao BC, Subramaniam S, Chiu CH, Mersiades AJ, Ho CC, Brown C, Lai CL, Hughes BGM, Yang TY, O'Byrne K, Luo YH, Yip S, Ho CL, Bray V, Su WC, Moore M, Feng WL, Bai YY, Ford K, Cummins MM, Stockler MR, Solomon BJ, John T, Chih-Hsin Yang J. Durvalumab, Tremelimumab, and Platinum Chemotherapy in EGFR Mutation-Positive NSCLC: An Open-Label Phase 2 Trial (ILLUMINATE). JTO Clin Res Rep. 2024 Nov 22;6(2):100771. doi: 10.1016/j.jtocrr.2024.100771. eCollection 2025 Feb.

    PubMed 39877028

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tremelimumab and Durvalumab in people with EGFR Mutant Advanced Non Small Cell Lung Cancer, run by University of Sydney at 16 sites in 2 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 20 inclusion and 33 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: status not confirmed, as of the sponsor's last update on 21 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Australia, Taiwan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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?

Objective tumour response rate (OTRR) and Objective tumour response (OTR) (time frame: 36 months post enrolment of first participant.). 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 NCT03994393, 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 21 Apr 2023.

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