1627P - PET-imaging with 89Zr-labeled anti-mesothelin (MSLN) antibody in patients with pancreatic cancer (PC) or ovarian cancer (OC)

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Ovarian Cancer
Pancreatic Cancer
Imaging, Diagnosis and Staging
Translational Research
Presenter Laetitia Lamberts
Citation Annals of Oncology (2014) 25 (suppl_4): iv546-iv563. 10.1093/annonc/mdu358
Authors L.E. Lamberts1, C.W. Menke-van der Houven van Oordt2, F. Bensch1, J. Voortman3, O. Hoekstra4, D. Maslyar5, S.P. Williams5, B.M. Fine5, A.H. Bongaerts6, J.A. Gietema7, C.P. Schroder1, E.J. Ter Weele8, M.N. Lub-De Hooge9, H.M. Verheul10, S. Sanabria5, A.W.J.M. Glaudemans11, E. De Vries1
  • 1Medical Oncology, University Medical Center Groningen, 9713GZ - Groningen/NL
  • 2Medical Oncology, Vrije University Medical Centre (VUMC), NL-1081 HV - Amsterdam/NL
  • 3Medical Oncology, Vrije University Medical Centre (VUMC), Amsterdam/NL
  • 4Nuclear Medicine, Vrije University Medical Centre (VUMC), NL-1081 HV - Amsterdam/NL
  • 5Gred, Genentech, 94080 - South San Francisco/US
  • 6Radiology, University Medical Center Groningen, 9713GZ - Groningen/NL
  • 7Medical Oncology, University Medical Center Groningen, Groningen/NL
  • 8Hospital Pharmacy, University Medical Center Groningen, 9713GZ - Groningen/NL
  • 9Department Of Hospital And Clinical Pharmacy And Nuclear Medicine And Molecular Imaging, University Medical Center Groningen, NL-9713 GZ - Groningen/NL
  • 10Department Of Medical Oncology, VU University Medical Center, Amsterdam/NL
  • 11Department Of Nuclear Medicine And Molecular Imaging, University Medical Center Groningen, NL-9713 GZ - Groningen/NL

Abstract

Aim

The tumor antigen MSLN is frequently overexpressed in PC and OC. A 89Zr-PET study (NCT01832116) with MMOT0530A, an anti-MSLN antibody, was initiated in conjunction with a phase 1 study of the antibody-drug conjugate DMOT4039A (containing MMOT0530A linked to the anti-mitotic agent MMAE, NCT01469793). This imaging study aims to investigate antibody tumor uptake, whole body distribution and organ pharmacokinetics and to explore the relation between uptake and MSLN expression and response to DMOT40392A treatment in patients with unresectable PC or platinum-resistant OC.

Methods

Before receiving DMOT4039A, patients were injected with 37 MBq 89Zr-MMOT0530A +/- additional unlabeled MMOT0530A, followed by PET/CT imaging 2, 4 and 7 days post injection (pi). Tracer uptake was quantified with standardized uptake value (SUV) and expressed as mean (±SD). MSLN expression was determined in archival tumor tissue with an exploratory immunohistochemical (IHC) assay.

Results

7 PC and 4 OC patients were included. MSLN expression varied from 0 to 3+. The optimal antibody protein dose resulting in sufficient circulating tracer was 10 mg MMOT0530A and the optimal imaging time was 4 or 7 days pi. Tumor tracer uptake was observed in 37 quantifiable tumor lesions (all patients) with mean SUV of 10.7 (±6.3) on PET 4 days pi. The mean SUV per patient (1-8 lesions/patient) was 10.9 (±5.7), with 9.2 (±4.5) in PC and 11.9 (±7.4) in OC lesions on PET 4 days pi. Within patients, a mean 2.4-fold (±1.10) difference in tumor uptake between lesions was found. Two measurable lesions on diagnostic CT (according to RECIST 1.1) were not visible on PET. Uptake in blood, liver, kidneys, spleen and intestine reflected normal antibody distribution with mean SUV at day 4 pi of 5.6, 7.8, 6.1, 4.1 and 3.2, respectively, while low uptake was observed in muscle, lung, brain and bone (0.6, 1.0, 0.2 and 0.7, respectively). Tracer tumor uptake was lower in the 2 patients with IHC scores 0 and 1. Best response on DMOT4039A was stable disease in ten patients. An association between iPET tumor uptake and clinical response could not be determined.

Conclusions

89Zr-MMOT0530A-PET shows antibody uptake in primary and metastatic PC and OC tumor lesions. This technique can potentially guide antibody-based therapy development.

Disclosure

D. Maslyar: I am employed by Genentech, Inc and I have stock ownership in Roche; S.P. Williams: I am employed by Genentech, Inc and I have stock ownership in Roche; B.M. Fine: I am employed by Genentech, Inc and I have stock ownership in Roche; J.A. Gietema: I have received research funding from Roche, Abbvie and Siemens, but not for this trial; S. Sanabria: I am employed by Genentech, Inc and I have stock ownership in Roche, E. De Vries: Financial support was made available from Genentech to the UMCG for trial execution. All other authors have declared no conflicts of interest.