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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04297748




Registration number
NCT04297748
Ethics application status
Date submitted
4/03/2020
Date registered
5/03/2020
Date last updated
23/06/2020

Titles & IDs
Public title
Bioimaging Study of 89Zr-M7824 in NSCLC
Scientific title
A Bioimaging Study of 89Zr-M7824 PET Scans in Patients With Advanced or Metastatic NSCLC Receiving M7824 Alone or in Combination With Chemotherapy
Secondary ID [1] 0 0
ONJ2018-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Combination Product - 89Zirconium-M7824
Treatment: Drugs - M7824

Experimental: Cohort A - Patients (pts) will receive an initial trace (100 mg, IV) dose of zirconium-89 (1.8-2.5 mCi) labelled M7824 (89Zr-M7824) on day 1, sequential PET imaging over 1 week will be performed to determine the biodistribution 89Zr-M7824 into the tumour and normal tissues. All patients who remain on study after Day 14 will have a 1200 mg dose of M7824 q2w beginning on Cycle 1 Day 15. Pts will then receive a 2nd infusion of 100 mg of 89Zr-M7824 with cold M7824 making a total dose of 1200mg on Day 29. All patients will then receive a dose of cold 1200mg M7824 on Cycle 1 Day 43. Patients will continue to receive a therapeutic dose of 1200 mg q2w of M7824 until disease progression or unacceptable toxicity. Patients who do not achieve a CR after 3 doses of M7824 in Cycle 1, may then commence treatment with concurrent chemotherapy with carboplatin and pemetrexed at conventional doses.

Experimental: Cohort B - Cohort A will determine whether or not high PD-L1 positive disease is required at study entry to Cohort B. All other assessments within cohort A will be undertaken.


Combination Product: 89Zirconium-M7824
PET imaging agent

Treatment: Drugs: M7824
Bifunctional fusion protein intended to block PD-L1 and neutralize TGFbeta simultaneously.

Intervention code [1] 0 0
Combination Product
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Biodistribution of 89Zr-M7824 in NSCLC patients - The biodistribution of 89Zr-M7824 will be evaluated by qualitative assessment of organ uptake and clearance from PET imaging following infusion of 89Zr-M7824. Patterns of expected normal tissue uptake due to blood pool activity, and PD-L1 expression, as well as catabolism of 89Zr-M7824, will be assessed.
Timepoint [1] 0 0
Cycle 1 - 7 weeks
Secondary outcome [1] 0 0
Number of participants with 89Zr-M7824 treatment-related adverse events as assessed using CTCAE v5.0. - Adverse responses of any grade following commencement of treatment will be recorded and quantified.
Timepoint [1] 0 0
0-12 months
Secondary outcome [2] 0 0
Number of participants with M7824 or M7824 combined with chemotherapy treatment-related adverse events as assessed using CTCAE v5.0. - Adverse responses of any grade following commencement of treatment will be recorded and quantified.
Timepoint [2] 0 0
0-36 months

Eligibility
Key inclusion criteria
- Adults (= 18 years) with histologically proven advanced NSCLC

- PD-L1 positive staining in > 1% of tumour cells in archival or fresh tissue (may be
modified for Cohort B to require PDL1-high status and/or PD-L1 status to be tested on
fresh tissue obtained a study entry, based on evaluation of data from Cohort A)

- Measurable disease by RECIST 1.1

- ECOG 0-1

- Expected survival more than 3 months

- Adequate organ function. Out of range values that are not clinically significant will
be permitted, except for the following laboratory parameters, which must be within the
ranges specified:

Hemoglobin = 9 g/dL Neutrophils = 1.5 x 109/L Platelets = 100 x 109/L INR = 1.4 Serum
creatinine =1.3 x ULN Estimated creatinine clearance = 30 ml/min according to the Cockcroft
Gault formula or local normal range Serum AST and ALT =2.5 x ULN Serum bilirubin = 1.5 x
ULN Available archived formalin-fixed paraffin embedded or frozen tumour tissue; or
consents to tumour biopsy at enrolment (the latter is strongly preferred) Presence of a
suitable reference tumour lesion for PET imaging i.e. measuring > 1.5cm and not located in
the mediastinum
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior systemic immunotherapy for advanced NSCLC

- Patients who are unsuitable for chemotherapy in the investigator's judgement

- The participant's tumour harbors an EGFR sensitizing (activating) mutation, ALK
translocation, ROS1 rearrangement, or BRAF V600E mutation

- Use of anti-cancer therapy including surgery, chemotherapy, immunotherapy,
radiotherapy to a non-thoracic site or any investigational therapy within 28 days
prior to Study Day 1

- Has received thoracic radiotherapy > 30 Gy within 6 months of the dose of study drug

- Previous malignant disease (other than NSCLC) within the last 3 years. Participants
with a history of cervical carcinoma in situ, superficial or non-invasive bladder
cancer, or basal cell or squamous cell carcinoma in situ previously treated with
curative intent are NOT excluded. Participants with other localized malignancies
treated with curative intent need to be discussed with the Medical Monitor.

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
Crossover
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
3078 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Olivia Newton-John Cancer Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Merck Healthcare KGaA
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Austin Health
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a bioimaging study of 89Zr-M7824 PET scans in patients with advanced or metastatic
non-small cell lung cancer who will be receiving M7824 alone or with standard of care
chemotherapy. M7824 is a bifunctional fusion protein that combines an anti-PD-L1 antibody and
the extracellular domain of TGFß receptor II (TGFßRII) as a TGFß neutralizing 'trap', into a
single molecule.
Trial website
https://clinicaltrials.gov/show/NCT04297748
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Hui K Gan, MBBS
Address 0 0
Austin Health
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jodie Palmer, PhD
Address 0 0
Country 0 0
Phone 0 0
+61394963573
Fax 0 0
Email 0 0
jodie.palmer@onjcri.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04297748