Abstract CT132: iPREDICT trial: A phase IIb, open label study of 89Zr-Crefmirlimab Berdoxam PET/CT in subjects with selected advanced malignancies (melanoma, merkel cell, renal cell and non-small cell lung cancers), scheduled to receive standard-of-care immunotherapy, to predict response to therapy

Abstract Background: Immunotherapy (IOT) of cancer depends on intratumoral CD8+ cells overcoming multiple obstacles to their localization and function. CD8+ cell content and its changes with treatment are important to understand tumor immunobiology, prognosis, and to guide therapy. Trial design: ImaginAb has developed an imaging agent, 89Zr-crefmirlimab berdoxam (formerly 89Zr-Df-IAB22M2C/89Zr-Df-crefmirlimab), with an 80 kDa minibody lacking a functional Fc domain, conferring high affinity to CD8, conjugated via deferoxamine to 89Zr for PET imaging: specific binding is to both CD8αα and CD8αβ, facilitating recognition of mature CD8+ cells and a small number of other cell types expressing CD8. The minibody structure was optimized for organ perfusion and pharmacokinetics, thereby maximizing the signal-to-background ratio. The long T1/2 (~3 d) of 89Zr permits repeat scanning during the week following an infusion. A previous Phase I study of single-dose 89Zr-crefmirlimab berdoxam was designed to select the optimum Phase II dose [Pandit-Taskar et al J Nuc Med 2020; Farwell et al J Nuc Med 2021]. After establishing the lack of toxicity across several dose levels, 1 mCi of 89Zr and 1.5 mg of minibody are now being used in Phase II studies. Our recently-completed Ph IIA study was designed to test the correlation of CD8+ cells in tumor biopsies with CD8 PET/CT before and during IOT in several tumor types routinely treated with IOT (including melanoma, renal, driver oncogene-negative lung). The present Ph IIB study, (first patient/first visit accomplished in 12/2021) tests the correlation of CD8 PET/CT with subject response by RECIST 1.1 (primary objective), and with lesion response (secondary objective). Adults with solid tumors receive 89Zr-crefmirlimab berdoxam i.v. and undergo PET-CT scan 24 hours later (non-contrast CT for localization). IOT (usually one or two immune checkpoint antibodies, using most commonly-used standard-of-care regimen for the disease) is then initiated. A second 89Zr-crefmirlimab berdoxam infusion and PET/CT are performed 4-6 weeks after the start of IOT followed 6-8 weeks later by standard tumor assessments (preferably CT with i.v. contrast to obtain RECIST-qualifying measurements). Thereafter, IOT and standard tumor assessments are continued according to standard practice and data for the present study collected up to 12 months after the start of treatment. For participants who progress on treatment there is an optional third 89Zr-crefmirlimab berdoxam infusion and PET/CT. For all participants optional biopsies are collected to coincide with PET/CT timepoints. Accrual is ongoing at three sites in USA, and up to 20 sites globally (USA, Europe and Australia) will participate. The overall accrual goal is 80 patients, distributed across the four tumor types. Citation Format: Kim Margolin, David Hays, Delphine L. Chen, Gary Ulaner, Ron Korn, Katherine Young, Michael Ferris, William Le, Ian Wilson. iPREDICT trial: A phase IIb, open label study of 89Zr-Crefmirlimab Berdoxam PET/CT in subjects with selected advanced malignancies (melanoma, merkel cell, renal cell and non-small cell lung cancers), scheduled to receive standard-of-care immunotherapy, to predict response to therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT132.