Abstract
Squamous cell carcinoma of the anorectal canal (SCCA) is a rare HPV-related malignancy that is steadily increasing in incidence. A high unmet need exists for patients with persistent loco-regional and metastatic disease. Axalimogene filolisbac (ADXS11-001) is an investigational immunotherapy that stimulates tumor-specific responses against HPV-associated cancers, and has demonstrated benefit in metastatic cervical cancer. We conducted this single-arm, multicenter, phase 2 trial in patients with persistent/recurrent, loco-regional or metastatic SCCA. Patients received ADXS11-001, 1 × 109 colony-forming units intravenously every 3 weeks. A Simon 2-stage design was used to test primary co-endpoints of overall response rate (ORR) and 6-month progression-free survival (PFS) rate. Study would proceed to full enrollment if ORR ≥ 10% or 6-month PFS rate ≥ 20%. Thirty-six patients were treated; 29 patients were evaluable for response. One patient had a prolonged partial response (3.4% ORR). The 6-month PFS rate was 15.5%. Grade 3 adverse event were noted in 10 patients, with the majority being cytokine-release symptoms; one grade 4 adverse event was noted. No grade 5 adverse events occurred. ADXS11-001 was safe and well-tolerated in patients with SCCA. However, this study did not meet either primary endpoint. ADXS11-001 may be more beneficial when administered in combination with other cytotoxic or targeted agents.
Highlights
It is estimated that approximately 8600 new cases of anal cancer will be diagnosed in the United States in 2019, and 1160 people will die from the disease [1, 2]
We report here the first-in-human study to assess tumor response and safety of ADXS11-001 in patients with previously treated advanced squamous cell carcinoma of the anal canal (SCCA)
Thirty-nine patients were screened from May 2016 to December 2016; three patients were screen failures
Summary
It is estimated that approximately 8600 new cases of anal cancer will be diagnosed in the United States in 2019, and 1160 people will die from the disease [1, 2]. Accounting for less than 1% of all malignancies, anal cancer has been increasing in incidence by 2.2% per year for the past decade, while annual death rates increased by 2.9% per year from 2005 to 2014 [1]. Most patients with localized SCCA (stage I-III) can be cured by chemoradiation [4, 5], up to 25% of patients develop distant metastases (Stage IV disease) [6, 7]. A single arm phase II trial of docetaxel, cisplatin, and 5-fluoruracil (5-FU) in treatment naïve patients resulted an impressive response rate of 89% [9]. A small www.oncotarget.com randomized phase II trial compared 5-FU plus cisplatin vs carboplatin plus paclitaxel noting equivalent response rates of 57% vs 59%, respectively [10]
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