Dacomitinib (PF-0299804) in untreated patients (pts) with advanced or metastatic penile squamous cell carcinoma (PSCC): Early findings of an open-label, single-group, phase II trial (HER-Uro01)

384 Background: Prognosis of pts with advanced/metastatic PSCC is poor and chemotherapy exerts a low efficacy. PSCC is consistently depending on the epidermal growth-factor receptor (EGFR) pathway and early signals of activity of anti-EGFR targeting have been reported. Dacomitinib is a potent, irreversible TKI of human EGFR/HER1, HER2 and HER4. The primary objective of the trial will be to investigate the activity of PF-0299804 until surgical removal of nodal disease (locally-advanced setting) or until disease progression/onset of unacceptable toxicity (metastatic setting) (ClinicalTrials.gov NCT01728233). Methods: 37 pts with clinical N2-3or metastatic disease will receive oral dacomitinib 45 mg daily. Further eligibility requirements are ECOG-PS≤1, locoregional relapse after prior surgery, and no prior systemic therapy. Computed tomography (CT) and PET scans are scheduled at baseline and every 2 months. Simon’s Optimal 2-stage design is applied. The primary endpoint is the response-rate (CR/PR according to RECIST v1.1, H1:20%, H0: 5%). In stage 1, 12 evaluable patients will be accrued. Results: From 06/13 to 07/14, 9 pts were enrolled. Median age was 55 yrs (IQR: 54-72). 4 had received inguinal/pelvic lymphadenectomy, 4 had inguinal+pelvic nodes, 7 bilateral disease, and 2 distant mets. One patient achieved a PR, 6 a SD, 2 PD. 5 pts had a metabolic PR. After a median follow-up of 5 months, 4 pts (44.4%) are still progression-free (2-month PFS was 77.8%, 95%CI: 36.5-93.9). Skin toxicity was observed in 5 cases (4 G1, 1 G3), G2 diarrhea in two, and bleeding of cutaneous mets in one case. Conclusions: The minimum requirements to move to the second stage and full accrual have been met. Dacomitinib is showing activity in patients with PSCC. Further understanding of drug activity will come from the body of translational imaging and molecular characterization of tumors from enrolled patients. Clinical trial information: NCT01728233.