A Phase 0 Study to Assess the Biodistribution and Pharmacokinetics of a Radiolabeled Antibody Targeting Human Kallikrein 2 in Participants with Metastatic Castration-Resistant Prostate Cancer

Despite the inclusion of multiple agents within the prostate cancer treatment landscape, new treatment options are needed to address the unmet need for patients with metastatic castration -resistant prostate cancer (mCRPC). Although prostate -specific membrane antigen is the only cell -surface target to yield clinical benefit in men with advanced prostate cancer, additional targets may further advance targeted immune, cytotoxic, radiopharmaceutical, and other tumor -directed therapies for these patients. Human kallikrein 2 (hK2) is a novel prostate -specific target with little to no expression in nonprostate tissues. This first -in -human phase 0 trial uses an 111 In-radiolabeled anti-hK2 monoclonal antibody, [ 111 In]-DOTA-h11B6, to credential hK2 as a potential target for prostate cancer treatment. Methods: Participants with progressive mCRPC received a single infusion of 2 mg of [ 111 In]-DOTA-h11B6 (185 MBq of 111 In), with or without 8 mg of unlabeled h11B6 to assess antibody mass effects. Sequential imaging and serial blood samples were collected to determine [ 111 In]- DOTA-h11B6 biodistribution, dosimetry, serum radioactivity, and pharmacokinetics. Safety was assessed within a 2 -wk follow-up period from the time of [ 111 In]-DOTA-h11B6 administration. Results: Twenty-two participants received [ 111 In]-DOTA-h11B6 and are included in this analysis. Within 6-8 d of administration, [ 111 In]-DOTA-h11B6 visibly accumulated in known mCRPC lesions, with limited uptake in other organs. Two treatment -emergent adverse events unrelated to treatment occurred, including tumor -related bleeding in 1 patient, which led to early study discontinuation. Serum clearance, biodistribution, and tumor targeting were independent of total antibody mass (2 or 10 mg). Conclusion: This first -in -human study demonstrates that tumor -associated hK2 can be identified and targeted using h11B6 as a platform as the h11B6 antibody selectively accumulated in mCRPC metastases with mass -independent clearance kinetics. These data support the feasibility of hK2 as a target for imaging and hK2-directed agents as potential therapies in patients with mCRPC.