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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03994393




Registration number
NCT03994393
Ethics application status
Date submitted
20/06/2019
Date registered
21/06/2019
Date last updated
21/04/2023

Titles & IDs
Public title
Non Small Cell Lung Cancer Trial of Durvalumab and Tremelimumab in Advanced Epidermal Growth Factor Receptor (EGFR) Mutant Disease.
Scientific 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)
Secondary ID [1] 0 0
ALTG 16/009
Secondary ID [2] 0 0
CTC 0209
Universal Trial Number (UTN)
Trial acronym
ILLUMINATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
EGFR Mutant Advanced Non Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tremelimumab
Treatment: Drugs - Durvalumab

Active Comparator: Cohort 1 - Participants with no evidence of T790M

Active Comparator: Cohort 2 - Participants with evidence of T790M


Treatment: Drugs: Tremelimumab
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.

Treatment: Drugs: Durvalumab
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective tumour response rate (OTRR) and Objective tumour response (OTR)
Timepoint [1] 0 0
36 months post enrolment of first participant.
Secondary outcome [1] 0 0
Disease control (Disease Control Rate (DCR)
Timepoint [1] 0 0
36 months post enrolment of first participant.
Secondary outcome [2] 0 0
Objective tumour response rate (OTRR) & Objective tumour response (OTR)
Timepoint [2] 0 0
36 months post enrolment of first participant.
Secondary outcome [3] 0 0
Progression-free survival (PFS)
Timepoint [3] 0 0
36 months post enrolment of first participant.
Secondary outcome [4] 0 0
Progression-free survival at 12 months (PFS12)
Timepoint [4] 0 0
12 months post enrolment of last participant.
Secondary outcome [5] 0 0
Overall survival (OS)
Timepoint [5] 0 0
36 months from enrolment of first participant.
Secondary outcome [6] 0 0
Number and Severity (assessed as a composite) of Adverse Events
Timepoint [6] 0 0
36 months post enrolment of first participant.

Eligibility
Key inclusion criteria
1. 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.

2. Disease that has progressed and either:

(i) 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

3. Measurable disease according to RECIST 1.1

4. ECOG performance status of 0 or 1

5. 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

6. 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

7. 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

8. 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.

9. Evidence of post-menopausal status or negative urinary or serum pregnancy test for
female pre-menopausal patients.

10. 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.

11. Signed written informed consent (main study and optional biobanking).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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).

2. Mixed histology with any small cell or squamous component.

3. Life expectancy of less than 3 months.

4. 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.

5. 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.

6. 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.

7. History of pneumonitis or pulmonary fibrosis with clinically significant impairment of
pulmonary function.

8. History of active primary immunodeficiency or allogeneic transplant.

9. 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

10. Concurrent illness, including severe infection that may jeopardise the ability of the
patient to undergo the procedures outlined in this protocol with reasonable safety.

11. 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.

12. 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.

13. 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.

14. 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)

15. 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.

16. Serious medical or psychiatric conditions that might limit the ability of the patient
to comply with the protocol.

17. 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.

18. Known allergy or hypersensitivity to any of the study drugs or excipients.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/10/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/01/2024
Actual
Sample size
Target
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC
Recruitment hospital [1] 0 0
St George Hospital - Kogarah
Recruitment hospital [2] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [7] 0 0
Monash Medical Centre - Clayton - Clayton
Recruitment hospital [8] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [9] 0 0
St Vincent's Hospital (Melbourne) - Melbourne
Recruitment postcode(s) [1] 0 0
- Kogarah
Recruitment postcode(s) [2] 0 0
- Liverpool
Recruitment postcode(s) [3] 0 0
- Chermside
Recruitment postcode(s) [4] 0 0
- Woolloongabba
Recruitment postcode(s) [5] 0 0
- Bedford Park
Recruitment postcode(s) [6] 0 0
- Hobart
Recruitment postcode(s) [7] 0 0
- Clayton
Recruitment postcode(s) [8] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Taiwan
State/province [1] 0 0
Chiayi City
Country [2] 0 0
Taiwan
State/province [2] 0 0
Taichung
Country [3] 0 0
Taiwan
State/province [3] 0 0
Tainan
Country [4] 0 0
Taiwan
State/province [4] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Other
Name
University of Sydney
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
AstraZeneca
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Australasian Lung Cancer Trials Group
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief 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..

Study population:

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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT03994393
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Chee K Lee
Address 0 0
St George Hospital, Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03994393