Bioimaging Study of 89Zr-M7824 in NSCLC

NCT04297748 | Terminated Phase 1

• 1 other identifier: ONJ2018-001
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

PD-L1; TGF-beta; 89Zr-PET

Outcome Measures

Primary Outcomes (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.

  Cycle 1 - 7 weeks

Secondary Outcomes (2)

• Number of participants with 89Zr-M7824 treatment-related adverse events as assessed using CTCAE v5.0.

  0-12 months

• Number of participants with M7824 or M7824 combined with chemotherapy treatment-related adverse events as assessed using CTCAE v5.0.

  0-36 months

Other Outcomes (3)

• Clinical outcomes assessed via response evaluation criteria in solid tumors (RECIST) V1.1

  0-36 months

• Correlation of clinical outcome of monotherapy with M7824 (assessed via RECIST) with tumour uptake of 89Zr-M7824 as quantified by PET imaging.

  0-12 months

• Quantification of PD-L1 expression IHC and tumour uptake in a given lesion as measured by 89Zr-M7824 biodistribution.

  0-12 months

Study Arms (2)

Cohort A

EXPERIMENTAL

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.

Combination Product: 89Zirconium-M7824; Drug: M7824

Cohort B

EXPERIMENTAL

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; Drug: M7824

Interventions

89Zirconium-M7824 COMBINATION_PRODUCT

PET imaging agent

Cohort A; Cohort B

M7824 DRUG

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

Also known as: bintrafusp alfa

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Olivia Newton-John Cancer Research Institute: lead
• Merck Healthcare KGaA: collaborator
• Austin Health: collaborator

Study Sites (1)

Austin Health

Heidelberg, Victoria, 3078, Australia

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Camurati-Engelmann Syndrome

Interventions

bintrafusp alfa protein, human

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Hui K Gan, MBBS

  Austin Health

  PRINCIPAL INVESTIGATOR

• Andrew M Scott, MBBS

  Austin Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study will enroll into two sequential cohorts A and B

Study Record Dates

• First Submitted: March 4, 2020
• First Posted: March 5, 2020
• Study Start: June 1, 2020
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: January 17, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)