731 A first-in-human trial of an integrin beta-6 targeted antibody-drug conjugate (ADC), SGN-B6A, in patients with advanced solid tumors: interim results of a phase 1 study (SGNB6A-001)

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Background

Integrin beta-6 plays a role in tumor pathogenesis and invasiveness, and is correlated with poor outcomes in several cancers, making it a therapeutic target of interest.1,2 SGN-B6A is an investigational vedotin ADC comprised of an integrin beta-6-directed monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable linker. SGN-B6A elicits antitumor activity through MMAE-mediated cytotoxicity, bystander effect, and immunogenic cell death.3 Herein, we present the first clinical data in Part A (dose escalation) of a Phase 1 clinical trial evaluating SGN-B6A.

Methods

SGNB6A-001 (NCT04389632) is a Phase 1, open-label, multicenter dose-escalation/expansion study evaluating the safety, pharmacokinetics, and antitumor activity of SGN-B6A (confirmed objective response per Response Evaluation Criteria in Solid Tumors v1.1) in adults with advanced solid tumors. Part A is enrolling patients with histologically or cytologically confirmed metastatic or unresectable solid tumors, relapsed or refractory disease or intolerance to standard-of-care therapies. Data for continuous weekly dosing (Days 1, 8, and 15 in a 21-day cycle [Q1W]) and intermittent dosing (Days 1 and 8 in a 21-day cycle [2Q3W]) are presented in this abstract.

Results

As of 10 May 2022, 30 patients in Q1W (0.8, 1.0, and 1.2 mg/kg) and 18 patients in 2Q3W (1.2 or 1.25 mg/kg) received SGN-B6A. Baseline demographics are outlined in Table 1. In Q1W, 1 dose limiting toxicity (DLT) of stomatitis (5.9%) was reported at the 1.2 mg/kg dose level (n=17; Table 2). The most common treatment-related adverse events (TRAEs) in Q1W across all doses (n=30) were fatigue (26.7%), peripheral sensory neuropathy (23.3%), alopecia (20%) and decreased appetite (20%). The most common Grade ≥ 3 TRAE reported across all dose groups was neutropenia (10%). In 2Q3W (n=18), two patients experienced DLTs (diarrhea, neutropenia, and rash maculo-papular [5.6%]). The most common TRAEs were alopecia, diarrhea, and peripheral sensory neuropathy (16.7% each), and the most common Grade ≥ 3 TRAEs were diarrhea, hyperglycemia, and neutropenia (11.1%). Objective responses were observed in Q1W and 2Q3W in several tumor types including non-small cell lung, head and neck squamous cell, esophageal, and cutaneous squamous cell cancer, starting at 1.2 mg/kg. Detailed efficacy results will be presented.

Conclusions

SGN-B6A at both dosing schedules demonstrated an acceptable safety profile, with more favorable tolerability at 2Q3W (table 2). Preliminary antitumor activity has been observed starting at 1.2 mg/kg. Enrollment in Part B (dose expansion) is ongoing.

Trial Registration

NCT04389632

References

Li F, Shang Y, Shi F, Zhang L, Yan J, Sun Q, She J. Expression of Integrin β6 and HAX-I Correlates with Aggressive Features and Poor Prognosis in Esophageal Squamous Cell Carcinoma. Cancer Management and Research. 2020;12:9599-9608 Elayadi A, Samli K-N, Prudkin L, Liu Y-H, Bian A, Xie X-J, Wistuba I.I, Roth J.A, McGuire M.J, Brown K.C. A Peptide Selected by Biopanning Identified the Integrin αvβ6 as a Prognostic Biomarker for Nonsmall Cell Lung Cancer. Cancer Res. 2007;67:(12) Klussman K, Tenn E-M, Higgins S, Mazahreh R, Snead K, Hamilton J, Grogan B, Sigurjonsson J, Cao A, Gardai S, Liu B. Vedotin ADCs Induce ER Stress and Elicit Hallmarks of ICD Across Multiple Cancer Indications. J Immunother Cancer. 2020;8(Suppl 3):A1–A559

Ethics Approval

The trial is being conducted in compliance with the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice. All patients, or their legal representatives, provided informed consent. All participating sites have been approved by a corresponding institutional review board or independent ethical committee per the participating institution.