Penile carcinoma is diagnosed fewer than 1 in 100,00 men each year, but is more common in parts of Asia, Africa, and South America. Although it is a rare tumor, penile squamous cell carcinoma (PSqCC) has poor prognosis and limited available treatment options for patients. Palliative platinum-based chemotherapy remains the standard of care, but it only offers a marginal survival benefit.
Recently, high levels of programmed death ligand 1 (PD-L1) have been detected in a majority of patients with PSqCC, indicating that immunotherapy treatment strategies could be beneficial for this patient population. Therefore, the ORPHEUS trial aims to evaluate the efficacy and safety of the INCMAGA00012, an antibody against programmed cell death protein 1 (PD1), in patients with unresectable, locally advanced or metastatic PSqCC.
The trial is an international, multicenter, single arm phase 2 clinical trial. Patients had to have radiologic evidence of locally advanced unresectable or metastatic stage 4 PSqCC, be treatment naïve or ≥1 prior chemotherapy or radiotherapy regimen, have measurable disease or evaluable disease per RECIST 1.1, and an ECOG Performance status of 0 or 1. Prior treatment with anti-PD1, anti-PD-L1, or anti-PD-L1 regimens was not allowed. Additionally, patients that had a diagnosis of immunodeficiency, ongoing treatment with systemic steroids or immunosuppressors, or had active central nervous system metastases and/or carcinomatous meningitis were ineligible for the trial.
A total of 18 patients from 13 sites across Spain and Italy, were enrolled and received 500 mg INCMGA00012 administered intravenously on day 1 of each 28-day cycle until disease progression, unacceptable toxicity, death, or study discontinuation for any other reason. Tumors were assessed every 8 weeks during the first 6 months and then every 12 weeks thereafter. The primary endpoint for the study was investigator-assessed overall response rate, with secondary endpoints of clinical benefit ratio, progression-free survival, 6-month progression-free survival, duration of response, overall survival, maximum tumor shrinkage, and number of treatment-related adverse events. The trial will additionally explore tumor- and immune-related factors associated with disease activity status or response to treatment and the impact of INCMGA00012 on HIV control in HIV-positive patients.
“New effective therapeutic approaches for this disease are urgently needed. Although new therapies are being evaluated in PSqCC, the low incidence of this tumor, and the scarce knowledge of its molecular alterations make it difficult to carry out clinical research that can really give rise to effective therapeutic strategies”, explained Xavier García del Muro, the scientific director of the trial, Medical Oncologist and Head of The Genito-Urinary Cancer Unit of the Institut Català de Oncologia (ICO).
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