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Non-Small Cell Lung CancerPhase 1/2NCT04297748

Bioimaging Study of 89Zr-M7824 in NSCLC

A Phase 1/2 study testing 89Zirconium-M7824 and M7824 in people with Non-Small Cell Lung Cancer, run by Olivia Newton-John Cancer Research Institute at 1 site in Australia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
89Zirconium-M7824 and M7824
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteAustralia
Study dates
1 Jun 2020to 30 Nov 2022
Phase
Phase 1/2
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 (≥ 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

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Australia1 site

  • Austin Health

    Heidelberg, Victoria, 3078

Other trials in Australia

About this study

Official title: A Bioimaging Study of 89Zr-M7824 PET Scans in Patients With Advanced or Metastatic NSCLC Receiving M7824 Alone or in Combination With Chemotherapy

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 TGFβ receptor II (TGFβRII) as a TGFβ neutralizing 'trap', into a single molecule.

Read the detailed description

Immune checkpoint inhibitors have shown improved treatment outcome in patients with NSCLC; however, there is room to further improve benefits. A novel agent such as M7824, a fusion protein which targets the tumor microenvironment where it blocks both the cell intrinsic PD-L1/PD-1 interaction and the immunosuppressive TGFβ, is hypothesized to be more effective than agents that target only a single pathway.

This study aims to investigate functional imaging with 89Zr-M7824 to characterize the biodistribution of M7824 to support its clinical development. In Part A, we will evaluate the biodistribution of zirconium-89 (89Zr) labelled M7824 in a small cohort of lung cancer patients unselected for PD-L1 status (n=3). In particular, we will examine the ability of 89Zr-M7824 to detect and quantitate intra-tumoural PD-L1 expression and correlate this with PD-L1 assessment in archival tissue. Based on this, Part B will gather additional data about the biodistribution of 89Zr-M7824 in an additional 9 patients. The requirement for patients in Part B to have high levels of PD-L1 positive cells in tumours based on a fresh biopsy or archival tissue at study entry will be informed by the data generated in Part A. Safety will be formally assessed also as a secondary endpoint at the end of Part A of the study and addressed if necessary. After completion of 2 imaging cycles, patients who do not show complete response to M7824 monotherapy after 3 therapeutic doses of M7824 may be transitioned to M7824/chemotherapy combination

Being tested
89Zirconium-M7824, M7824
Keywords
PD-L1, TGF-beta, 89Zr-PET
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Camurati-Engelmann Syndrome

What participants receive

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

  • 89Zirconium-M7824Combination product

    PET imaging agent

  • M7824Drug

    Also called bintrafusp alfa

    Bifunctional fusion protein intended to block PD-L1 and neutralize TGFbeta simultaneously.

Study groups in NCT04297748
Study groupRoleWhat they receive
Cohort AExperimentalPatients (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.
Receives: Combination Product: 89Zirconium-M7824; Drug: M7824
Cohort BExperimentalCohort 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.
Receives: Combination Product: 89Zirconium-M7824; Drug: M7824

What is being measured

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

  1. 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.

    Measured: Cycle 1 - 7 weeks

Secondary outcomes (2)

  1. 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.

    Measured: 0-12 months

  2. 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.

    Measured: 0-36 months

Timeline

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

  1. First posted5 Mar 2020
  2. Study start1 Jun 2020
  3. Primary completion30 Nov 2022
  4. Study completion30 Nov 2022

Why it stopped: Efficacy finding

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Crossover
Model description
The study will enroll into two sequential cohorts A and B
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04297748
Sponsor's protocol ID
ONJ2018-001
Status last verified
Jan 2023
First submitted
4 Mar 2020
Last updated
17 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing 89Zirconium-M7824 and M7824 in people with Non-Small Cell Lung Cancer, run by Olivia Newton-John Cancer Research Institute at 1 site in Australia.

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 7 inclusion and 6 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: stopped early, as of the sponsor's last update on 17 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. 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 combined 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.

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?

The study was stopped early (reason given: Efficacy finding). 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?

Biodistribution of 89Zr-M7824 in NSCLC patients (time frame: Cycle 1 - 7 weeks). 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 NCT04297748.

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 17 Jan 2023.

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