Bioimaging Study of 89Zr-M7824 in NSCLC

NCT ID: NCT04297748

Last Updated: 2023-01-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2022-11-30

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

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

89Zirconium-M7824

Intervention Type: COMBINATION_PRODUCT

PET imaging agent

M7824

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

89Zirconium-M7824

Intervention Type: COMBINATION_PRODUCT

PET imaging agent

M7824

Intervention Type: DRUG

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

Interventions

89Zirconium-M7824

PET imaging agent

Intervention Type: COMBINATION_PRODUCT

M7824

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

Intervention Type: DRUG

Other Intervention Names

bintrafusp alfa

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Healthcare KGaA

UNKNOWN

Sponsor Role: collaborator

Austin Health

OTHER_GOV

Sponsor Role: collaborator

Olivia Newton-John Cancer Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hui K Gan, MBBS

Role: PRINCIPAL_INVESTIGATOR

Austin Health

Andrew M Scott, MBBS

Role: PRINCIPAL_INVESTIGATOR

Austin Health

Locations

Austin Health

Heidelberg, Victoria, Australia

Countries

Australia

Other Identifiers

ONJ2018-001

Identifier Type: -

Identifier Source: org_study_id