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ORPHEUS Study: Evaluation of Retifanlimab In Penile Cancer

Updated: Dec 7, 2022

Squamous cell carcinoma (SqCC) is the most common primary neoplasm of the penis. However, due to its very low incidence in western countries (0.4-0.6%), penile SqCC (PSqCC) is nowadays considered a rare tumor. The etiology of this malignancy is multifactorial, being Human Papilloma Virus (HPV) infection the best characterized risk factor, detecting HPV DNA in a range between 30-80% of invasive penile cancers. Today, patients with advanced PScCC are a population with a poor prognosis, very limited treatment options, and a survival rate lower than one year.

In hopes of finding a safe and more effective therapeutic approach for advanced PSqCC, MEDSIR designed and sponsored the ORPHEUS study. In this trial, we will explore the clinical benefit of Retifanlimab, a highly selective anti- Programmed cell Death Protein-1 (PD-1) monoclonal antibody, in patients with advanced PSqCC. Unlike other ongoing studies, this trial will evaluate the activity of immunotherapy in a series of patients with advanced PSqCC regardless of their prior treatment and extension of the disease.

“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).

ORPHEUS, a new trial exploring an immunotherapy-based approach as an alternative to Standard Chemotherapy for penile cancers

Today, the standard of care for patients with advanced PSqCC is palliative chemotherapy, with very marginal benefits in term of survival (less than 1 year). ORPHEUS explores an immunotherapy-based alternative to standard chemotherapy, with the final goal to improve life expectancy for those men affected by an advanced stage malignancy.

Patients participating in the study will be treated with Retifanlimab, a monoclonal antibody targeting the Programmed cell Death Protein-1 (PD-1), blocking the PD-1 interaction with its ligand PD-L1, and thus stimulating the immune response against the tumor. Interestingly, the majority of PSqCC tumors express PD-L1, whose presence is associated to a good response to immunotherapy. Moreover, a recent study showed that PSqCC genotype is highly comparable to other squamous cell tumors induced by HPV, which showed promising results when treated with immunotherapies.

The encouraging antitumor activity exerted by retifanlimab in other squamous cell carcinomas, such as head and neck and lung cancers, makes reasonable to experiment this treatment in an advanced setting of PSqCC patients.

As a primary objective, ORPHEUS will assess the percentage of patients who experience tumor shrinkage after treatment with reftifanlimab, according to RECIST criteria. As secondary objectives, Clinical Benefit Rate, Progression Free Survival, Duration of Response, Time to Progression, Overall Survival, and maximum tumor shrinkage will be assessed as parameters of drug efficacy, together with evaluation of drug safety and tolerability.

The ORPHEUS study, which is currently under recruitment, is a multicenter phase II trial, carried out among 10 Spanish reference hospitals, such as the ICO-Hospitalet and the Hospital de Sant Pau in Barcelona, the October 12th in Madrid, the Miguel Servet of Zaragoza, and the Hospital Virgen del Rocío in Sevilla.

ORPHEUS, designed and sponsored by MEDSIR, offers a new immunotherapy-based approach for patients with advanced PSqCC, a malignancy in urgent need of novel therapeutic insights.

If you would like to know more about us or about this clinical trial or other MEDSIR-sponsored studies, do not hesitate to contact us.

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