1150TiP - A phase II, open-label, multi-dose study of [89Zr]Zr-Df-IAB22M2C (CD8 cell PET tracer) PET/CT in patients with selected advanced or metastatic solid malignancies scheduled to receive standard of care immunotherapy, as single agent or in combination

Background

Immunotherapy (IOT) of cancer depends on intratumoral CD8+ cells that can overcome 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]Zr-Df-IAB22M2C, 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 radioactive T_1/2 (∼3 d) of ⁸⁹Zr permits repeat scanning over a week from infusion. A previous phase I study of single-dose [⁸⁹Zr]Zr-Df-IAB22M2C was designed to select the optimum clinical dose [Pandit-Taskar et al J Nuc Med 2020; Farwell et al, submitted]. After establishing safety across several dose levels, 1 mCi of ⁸⁹Zr and 1.5 mg of minibody are now being used in all studies. The ongoing phase IIA study was designed to test correlation of CD8+ cells in tumor biopsies with CD8 PET/CT before and during IOT. Adults with solid tumors undergo biopsy of a RECIST1.1-measurable lesion (or archival tissue is submitted), then receive [⁸⁹Zr]Zr-Df-IAB22M2C i.v. and are scanned 24 hours later via PET/CT, (non-contrast CT for localization). Standard IOT (usually one or two immune checkpoint antibodies) is then initiated. A second [⁸⁹Zr]Zr-Df-IAB22M2C infusion and PET/CT followed by biopsy are done 4-6 weeks after the start of IOT—this precedes by about 6-8 weeks the first tumor response assessment by standard evaluations. Accrual is ongoing at 15 U.S. centers to correlate biopsies with scans. Our next trial will be global and will study the correlation of CD8 ImmunoPET/CT scans with clinical outcomes (response or progression) of IOT in selected immunoresponsive tumors.

Clinical trial identification

NCT03802123; First posted January 14, 2019.

Editorial acknowledgement

Legal entity responsible for the study

ImaginAb.

Funding

ImaginAb.

Disclosure

K.A. Margolin: Financial Interests, Personal, Advisory Role: ImaginAb; Financial Interests, Personal, Advisory Role: Werewolf; Financial Interests, Personal, Advisory Board: Tentarix; Financial Interests, Personal, Advisory Board: Xilio; Financial Interests, Personal, Advisory Board: OncoSec; Financial Interests, Personal, Advisory Role: Checkmate Pharma. R. Korn: Financial Interests, Personal and Institutional, Member of the Board of Directors: Imaging Endpoints; Financial Interests, Personal, Advisory Role: ImaginAb. M. Farwell: Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal, Advisory Role: ImaginAb; Financial Interests, Personal and Institutional, Sponsor/Funding: ImaginAb; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Sponsor/Funding: Carisma; Financial Interests, Institutional, Research Grant: Carisma. M.A. Postow: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Array; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: InCyte; Financial Interests, Personal, Advisory Board: NewLink; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Institutional, Sponsor/Funding: RGenix; Financial Interests, Institutional, Sponsor/Funding: Infinity; Financial Interests, Institutional, Sponsor/Funding: BMS; Financial Interests, Institutional, Sponsor/Funding: Merck; Financial Interests, Institutional, Sponsor/Funding: Array; Financial Interests, Institutional, Sponsor/Funding: Novartis; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca. D. Hays: Financial Interests, Institutional, Principal Investigator: ImaginAb; Financial Interests, Personal and Institutional, Speaker’s Bureau: Sirtex. I.A. Wilson: Financial Interests, Institutional, Full or part-time Employment: ImaginAb. W.H. Le: Financial Interests, Institutional, Full or part-time Employment: ImaginAb.