Abstract CT045: A phase 1/2 trial of TAC-001 (TLR9 agonist-CD22 mAb) in advanced or metastatic solid tumors
Authors: Jason T. Henry, Anna C. Pavlick, Timothy Humphries, Sunnie Kim, Martin Gutierrez, Sarina A. Piha-Paul, Daniel Vaena, Shiraj Sen, Alexander Spira, Guru Sonpavde, Ons Harrabi, Feng Jin, Sangeetha Bollin, Laura QM Chow, Hong I. Wan, Cesar A. Perez
Journal: Cancer Research (2025)

Abstract Background: TAC-001 is a novel next-generation antibody-drug conjugate designed for systemic delivery of a potent Toll-like Receptor (TLR)-9 agonist payload. It selectively targets TLR9 to CD22+ B cells, triggering their activation and inducing anti-tumor responses by harnessing the immunological functions of B cells. The mouse surrogate of TAC-001 induced tumor infiltration of activated B cells, effector T cells, and TLS-like structures, leading to sustained anti-tumor activity, including in models resistant to anti-PD-1 therapy. Methods: This Phase 1 trial (INCLINE 101; NCT05399654) evaluated the safety, tolerability, pharmacokinetics (PK), immunogenicity, tumor biopsy pharmacodynamic (PD) effects, and preliminary efficacy of TAC-001 across multiple solid tumors with ECOG-PS 0-1. Eligible patients (pts; ≥18 years) received TAC-001 IV Q2W at 3-fold escalating doses (0.1-12 mg/kg) with monitoring for 28-day dose-limiting toxicities (DLTs). Doses were reduced 2-fold or to the next lower tolerated dose level in the event of DLTs. TAC-001 was evaluated in select tumor types at two doses at and below the maximum tolerable dose (MTD). Results: As of September 11, 2024, 72 heavily pre-treated pts (median age 62, range 37-79) with a median of 6 (range 1 to 12) prior therapies were enrolled in the study, including 52 (72%) PD-(L)1 refractory/resistant pts. Treatment-related adverse events (TRAE) were reported in 66 (92%) pts, with 54 (75%) experiencing mild-moderate (Gr 1-2) events. The most frequent TRAEs included chills (61%), fatigue (35%), and pyrexia (35%). Gr ≥ 3 toxicities occurred in 12 (17%) pts, leading to treatment discontinuation in one pt (1.4%). DLTs occurred at 3 mg/kg (1 pt Gr ≥3 bilirubin and elevated ALT) and 12 mg/kg (1 pt transient Gr 3 transaminitis, and 1 pt Gr ≥3 bilirubin with Gr 4 acute kidney injury). The MTD was established at 6mg/kg, with 3mg/kg and 6mg/kg selected for dose expansion. TAC-001 PK exposures (Cmax and AUC) exhibited dose-dependent increases over the dose range tested. Preliminary PD assessment demonstrated dose-dependent CD22 engagement, with activation of circulating B cells observed across dose levels. Among 68 response-evaluable pts, 24 achieved stable disease (≥2 months), 2 (melanoma and cholangiocarcinoma) had confirmed durable partial responses, and 32 had progressive disease. Final results will be presented at the meeting. Conclusion: TAC-001 showed a favorable safety profile, dose-dependent PK/PD activity, and anti-tumor activity in PD- (L)1 refractory pts. Citation Format: Jason T. Henry, Anna C. Pavlick, Timothy Humphries, Sunnie Kim, Martin Gutierrez, Sarina A. Piha-Paul, Daniel Vaena, Shiraj Sen, Alexander Spira, Guru Sonpavde, Ons Harrabi, Feng Jin, Sangeetha Bollin, Laura QM Chow, Hong I. Wan, Cesar A. Perez. A phase 1/2 trial of TAC-001 (TLR9 agonist-CD22 mAb) in advanced or metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT045.