Intratumoral epidermal growth factor receptor (EGFR) antisense (AS) DNA in recurrent squamous cell carcinoma of the head and neck (SCCHN): A phase I trial

Abstract

6009 Background: SCCHN is characterized by upregulation of the EGFR where EGFR expression levels in the tumor correlate with decreased survival. We developed a novel anti-EGFR therapy with a therapeutic gene consisting of an EGFR AS sequence under the control of the U6 promoter in a pNGVL backbone. We conducted a phase I clinical trial to evaluate the safety and biological effects of EGFR AS in patients with advanced SCCHN. Methods: Patients (pts) with recurrent SCCHN refractory to standard therapies with at least one evaluable and accessible lesion were enrolled in a phase I trial. EGFR AS dose was escalated in successive cohorts of pts (classic “3+3” design) in 6 dose levels: 60 μg, 120 μg, 240 μg, 480 μg, 960 μg and 1920 μg at a concentration of 1 μg/μL. Pts received weekly intratumoral injections of EGFR AS × 4 weeks. Tumors were biopsied before and after the completion of therapy. In addition to treatment response as assessed by tumor volume measurements (PET/CT), levels of target proteins and phosphoproteins were assessed in the tumors. Results: 17 pts were enrolled (median age: 57 years; 15 M / 2 F). No grade 3/4 or dose-limiting toxicities were noted. 4 grade 1 toxicities were reported: injection site pain/swelling (2), localized edema (1) and lethargy (1). EGFR AS was present in the tumor after injection as demonstrated by PCR. 5 pts (29%; 95% CI 10–56%) achieved an objective response (RECIST), including 2 CRs (pCRs confirmed by biopsy) and 3 PRs; 2 pts had stable disease as best response. Median duration of response was 4.5 months (3.0–23.1). Median survival for the entire cohort was 5.4 months with a median survival in responders of 7.9 months. 1 pt who achieved CR is alive without progression at 23.1+ months. Immunohistochemical studies demonstrated decreased EGFR in 2 pts with CR. Assessment of downstream signaling molecules is in progress. Conclusions: Intratumoral EGFR AS was safe and resulted in impressive antitumor activity in pts with recurrent, incurable SCCHN. We plan to study further the use of EGFR AS as an integral component in the curative therapy of SCCHN. No significant financial relationships to disclose.