Clinical trial NCT04297748: Bioimaging Study of 89Zr-M7824 in NSCLC
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: PD-L1
TGF-beta
89Zr-PET
Lead sponsor: Olivia Newton-John Cancer Research Institute
Sponsor class: OTHER
Collaborators: name: Merck Healthcare KGaA
name: Austin Health
First posted: 2020-03-05
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study will enroll into two sequential cohorts A and B
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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

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.

Primary outcomes:
measure: Biodistribution of 89Zr-M7824 in NSCLC patients
timeFrame: Cycle 1 - 7 weeks
Secondary outcomes:
measure: Number of participants with 89Zr-M7824 treatment-related adverse events as assessed using CTCAE v5.0.
timeFrame: 0-12 months
measure: Number of participants with M7824 or M7824 combined with chemotherapy treatment-related adverse events as assessed using CTCAE v5.0.
timeFrame: 0-36 months
Other outcomes:
measure: Clinical outcomes assessed via response evaluation criteria in solid tumors (RECIST) V1.1
timeFrame: 0-36 months
measure: Correlation of clinical outcome of monotherapy with M7824 (assessed via RECIST) with tumour uptake of 89Zr-M7824 as quantified by PET imaging.
timeFrame: 0-12 months
measure: Quantification of PD-L1 expression IHC and tumour uptake in a given lesion as measured by 89Zr-M7824 biodistribution.
timeFrame: 0-12 months
Locations:
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
Study officials:
affiliation: Austin Health
name: Hui K Gan, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Austin Health
name: Andrew M Scott, MBBS
role: PRINCIPAL_INVESTIGATOR
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