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.
Name: 89Zirconium-M7824
Name: M7824
Description: 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.
Measure: Biodistribution of 89Zr-M7824 in NSCLC patients Time: Cycle 1 - 7 weeksDescription: Adverse responses of any grade following commencement of treatment will be recorded and quantified.
Measure: Number of participants with 89Zr-M7824 treatment-related adverse events as assessed using CTCAE v5.0. Time: 0-12 monthsDescription: Adverse responses of any grade following commencement of treatment will be recorded and quantified.
Measure: Number of participants with M7824 or M7824 combined with chemotherapy treatment-related adverse events as assessed using CTCAE v5.0. Time: 0-36 monthsDescription: Describe response rates to M7824 monotherapy or M7824 combined with conventional chemotherapy, defined as number of patient achieving a complete disease response, partial disease response or stable disease response determined by medical imaging of tumours.
Measure: Clinical outcomes assessed via response evaluation criteria in solid tumors (RECIST) V1.1 Time: 0-36 monthsDescription: To determine association of response to M7824 monotherapy with tumour uptake of 89Zr-M7824.
Measure: Correlation of clinical outcome of monotherapy with M7824 (assessed via RECIST) with tumour uptake of 89Zr-M7824 as quantified by PET imaging. Time: 0-12 monthsDescription: To determine the association between PD-L1 expression determined by IHC and tumour uptake in a given lesion as measured by 89Zr-M7824 biodistribution.
Measure: Quantification of PD-L1 expression IHC and tumour uptake in a given lesion as measured by 89Zr-M7824 biodistribution. Time: 0-12 monthsAllocation: Non-Randomized
Crossover Assignment
There is one SNP
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. --- V600E ---