First-in-human study (FIH) of FS222, a next-generation tetravalent PD-L1/CD137 bispecific antibody: Safety, pharmacodynamics (PD), and antitumor activity in patients (pts) with advanced solid tumors including PD-1 refractory melanoma.

• DOI: 10.1200/jco.2024.42.16_suppl.2505
• Publication Date: 2024-06-14T13:51:15Z
• Authors: Elena Garralda; Arjun Oberoi; Guillermo de Velasco; Iván Victoria; David Pesantez; Inaki Eguren Sant...; Victor Moreno; Valentina Boni; Andres Cervantes; Valentina Gambard...; Tudor-Eliade Ciul...; Milana Bergamino ...; Delvys Rodriguez-...; Guzman Alonso; Laurentia Minea G...; Daniel Jones; Abhay Patki; Ignacio Melero
• Keywords: CD137; Pharmacodynamics; Bispecific antibody; Solid tumor

2505 Background: Most pts receiving immune checkpoint inhibitors do not respond to treatment or relapse. FS222 is a novel affinity optimized, tetravalent bispecific PD-L1/CD137 antibody. FS222’s structure allows for potent, PD-L1-dependent, CD137 activation across wide range of dose levels, and designed provide selective agonism in the tumor. We present data from ongoing, FIH, open-label, phase I trial advanced solid tumors. Methods: Pts with pretreated tumors received increasing doses an accelerated titration 3+3 design intravenously every 3 4 weeks (Q4W) until disease progression unacceptable toxicity. The primary endpoint was safety. Secondary exploratory endpoints included pharmacokinetics, PD antitumor activity (by Response Evaluation Criteria Solid Tumors [RECIST] 1.1). Results: As cut off (DCO) on 05Dec2023, total 104 had been treated schedules FIH study (NCT04740424). report interim results Q4W cohorts (N=90). Patients median age 61 years (31-88 years) 2 (1-7) regimens prior treatments. duration exposure 82.5 days (24 – 529 days). most common treatment-related AEs (TRAEs; >20% pts) were increased aspartate aminotransferase (AST) alanine (ALT), pyrexia, thrombocytopenia, asthenia, neutropenia. TRAEs grade ≥3 (≥10% AST (13.3%) ALT (11.1%). related serious (≥3 febrile neutropenia (5 pts, 5.6%); cytokine release syndrome, ALT, (all 3.3%). On-target pharmacology confirmed by presence dose-dependent target engagement, significant peripheral CD8 + T cell modulation tumor CD3 cells at multiple levels. At DCO, 20 (22.2%) remained treatment. Objective responses (CR, PR) observed melanoma, NSCLC, ovarian cancer, TNBC, liposarcoma colon ORR 15.7% evidence further enrichment dose. In post-PD-1 metastatic/advanced cutaneous melanoma 60% (9/15, all PRs - 7 confirmed) control rate 86.7% (13/15). Conclusions: antibody demonstrated broad doses. safety profile acceptable manageable. Encouraging anti-tumor observed, including patients PD-1 refractory melanoma. Next steps include optimization evaluation other types. Clinical information: NCT04740424 .