Phase 1 Study of the Tissue Factor–Targeting Antibody-Drug Conjugate XB002 in Patients with Advanced Solid Tumors (JEWEL-101): Design of Expansion Cohorts for Squamous Cell Carcinoma of the Head and Neck

Purpose/Objective(s)

Despite recent advancements in therapy, patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) have a relatively poor prognosis after chemotherapy and immune checkpoint inhibitors (ICIs), with a median survival of ∼9 months, highlighting a need for novel treatments. Tissue factor (TF) is a factor VII/VIIa receptor involved in initiating the extrinsic coagulation pathway, and its overexpression has been associated with poor prognosis in several tumor types, including SCCHN. XB002 is a novel antibody-drug conjugate (ADC) composed of a TF-targeting monoclonal antibody conjugated to zovodotin, an auristatin-based payload with a protease-cleavable linker. The zovodotin linker-payload is designed to lower off-target deconjugation vs other auristatin-based ADCs. In preclinical studies, XB002 displayed antitumor activity without affecting coagulation. The first-in-human, phase 1, open-label, multicenter JEWEL-101 study (NCT04925284) is evaluating XB002 in patients with advanced solid tumors. The maximum tolerated and/or recommended doses of XB002 alone and in combination with nivolumab or bevacizumab will be determined in a dose-escalation stage. Preliminary efficacy and safety will be determined in a tumor-specific cohort expansion stage. Here we present the design of the expansion stage for the SCCHN cohorts.

Materials/Methods

Patients in the SCCHN cohorts must have an inoperable, locally advanced, metastatic, or recurrent tumor, and an ECOG PS of 0–1. Patients must have measurable disease per RECIST v1.1, with the primary tumor located in the oral cavity, oropharynx, hypopharynx, or glottic larynx (nasopharyngeal carcinoma ineligible). Patient must have received 1–3 prior lines of therapy, including a prior platinum-containing chemotherapy and, if eligible and considered a local standard of care, prior ICI and/or anti-EGFR therapy. Additionally, radiographic progression during or following last systemic anticancer therapy is required. Prior treatment with TF-targeting or auristatin-based ADCs is not allowed, and patients with significant ocular disorders are excluded. Concomitant anticoagulants are permitted, and patients with peripheral neuropathy are eligible, provided it is grade <2 and does not impact activities of daily living. SCCHN patients will be randomized between 2 cohorts and will either receive XB002 alone or XB002 in combination with nivolumab. The primary outcome is objective response rate per RECIST v1.1 by investigator. Secondary outcomes include safety, pharmacokinetics, immunogenicity, progression-free survival, duration of response, and overall survival. Enrollment is ongoing with recruitment at sites in the United States, Europe, and the Asia-Pacific region.

Results

TBD

Conclusion

TBD