Efficacy of INCMGA00012 in Penile Squamous Cell Carcinoma (ORPHEUS)

NCT04231981 | Completed Phase 2 Results DMC

• 2 other identifiers: MedOPP2392019-001172-11
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 13

Brief Summary

This is a multicenter, open-label, single-arm, phase II clinical trial to evaluate the efficacy and safety of INCMGA00012 in Advanced Penile Squamous Cell Carcinoma

Conditions

Penile Cancer

Keywords

Penile Cancer; Penile squamous cell carcinoma; Locally advanced penile cancer; Metastatic penile cancer; Unresectable locally advanced penile cancer; Unresectable penile cancer; PSqCC; PSCC; Penile Cancer stage IV

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The primary efficacy endpoint for the study is the ORR. The ORR is defined as the number of patients with CR and PR divided by the number of patients in the analysis set. Tumor response will be defined as best response based on local investigator's assessment according to RECIST criteria v.1.1.

  From baseline until disease progression or treatment discontinuation, up to 10.3 months

Secondary Outcomes (7)

• Efficacy Determined by Clinical Benefit Rate (CBR)

  From baseline until disease progression or treatment discontinuation, up to 10.3 months

• Efficacy Determined by Progression-free Survival (PFS)

  From baseline until disease progression or treatment discontinuation, up to 10.3 months

• Efficacy Determined by 6-months PFS

  Baseline up to 6 months

• Efficacy Determined by Duration of Response (DoR)

  From baseline until disease progression or treatment discontinuation, up to 10.3 months

• Efficacy Determined by Overall Survival (OS)

  From baseline until disease progression or treatment discontinuation, up to 10.3 months

Study Arms (1)

Interventional arm

EXPERIMENTAL

Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.

Drug: Retifanlimab

Interventions

Retifanlimab DRUG

INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.

Also known as: INCMGA0012

Interventional arm

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients have been informed about the nature of study, and have agreed to participate in the study, and signed the informed consent form (ICF) prior to participation in any study-related activities.
• Male patients ≥ 18 years of age at the time of signing ICF.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.
• Life expectancy ≥12 weeks.
• Histologically-proven PSqCC.
• Locally advanced unresectable or metastatic stage 4 PSqCC that is not amenable to resection with curative intent (T4 or N3 or M1).
• Radiological evidence of locally advanced or metastatic disease.
• Patients must have measurable disease or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v.)1.1 criteria.
• Patients must agree to provide a tumor tissue sample from a metastatic site or the primary tumor at the time of study entry, with the exception of patients whom tumor biopsies cannot be obtained (e.g., inaccessible tumor or subject safety concern) that may submit an archived tumor specimen only upon agreement from the Sponsor. If feasible, patients will also be given the option of providing a tumor tissue sample at disease progression from metastasis or primary tumor (if tumor biopsies cannot be obtained for inaccessible lesion or subject safety concern).
• Adequate organ function:
• Hematological: White blood cell (WBC) count \> 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 75.0 x109/L, and hemoglobin \> 9.0 g/dL.
• Hepatic: Bilirubin ≤ 1.5 times the upper limit of normal (× ULN) (\< 3 x ULN in the case of Gilbert's disease); aspartate transaminase (AST), and alanine transaminase (ALT) ≤ 2.5 times × ULN (in the case of liver metastases ≤ 5 × ULN); Albumin \> 2.5 mg/mL.
• Renal: Serum creatinine ≤ 1.5 x ULN; alternately measured or calculated creatinine clearance ≥30 mL/min with creatinine levels \>1.5 × institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance).
• Coagulation: Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN and International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Locally PSqCC candidate for curative treatment.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Known hypersensitivity to any of the excipients of INCMGA00012.
• Receipt of anticancer therapy or participation in another interventional clinical study within 28 days before the first administration of study drug; 6 weeks for mitomycin C.
• Radiotherapy within 14 days of first dose of study treatment with the following caveat: 28 days for pelvic radiotherapy.
• Major surgery (defined as requiring general anesthesia) or significant traumatic injury within 4 weeks of start of study drug, or patients who have not recovered from the side effects of any major surgery, or patients who may require major surgery during the study.
• Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (e.g., radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.
• Cardiovascular: patients that have any of the following within 6 months of randomization: severe/unstable angina, myocardial infarction, symptomatic pericarditis, symptomatic congestive heart failure (New York Heart Association functional classification III-IV), cerebrovascular accident including transient ischemic attack, or symptomatic pulmonary embolism, coronary/peripheral artery bypass graft, ongoing cardiac dysrhythmias of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0 grade ≥2, including, ventricular arrhythmias -except for benign premature ventricular contractions-, supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication, any conduction abnormality requiring a pacemaker or any cardiac arrhythmia not controlled with medication.
• Metabolic: Uncontrolled hyper/hypothyroidism or diabetes mellitus type 1 (T1DM). Patients with hypothyroidism stable on hormone replacement will not be excluded from the trial. Patients with controlled T1DM on a stable insulin regimen may be eligible for this study.
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or immunosuppressive therapy within seven days prior to study treatment initiation.
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
• Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic steroid replacement therapy (≤ 10 mg prednisone daily) for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Prior allogenic stem cell or solid organ transplantation.
• Has received a live vaccine within 28 days of the planned start of study drug. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live-attenuated vaccines and are not allowed.
• Active/history of pneumonitis requiring treatment with steroids or active/history of interstitial lung disease.

Sponsors & Collaborators

• MedSIR: lead
• Incyte Biosciences International Sàrl: collaborator

Study Sites (13)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.

Milan, Italy

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

AUSL Reggio Emilia

Reggio Emilia, Italy

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

ICO-Hospitalet

L'Hospitalet de Llobregat, Spain

Location

Hospital Insular de Gran Canaria

Las Palmas de Gran Canaria, Spain

Location

Hospital 12 de octubre

Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital Virgen de la Arrixaca

Murcia, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, Spain

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Instituto Valenciano de Oncología

Valencia, Spain

Location

Hospital Miguel Servet

Zaragoza, Spain

Location

MeSH Terms

Conditions

Penile Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Penile Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Alicia Garcia
• Organization: MedSIR

alicia.garcia@medsir.org

+34 611261467

Study Officials

• Xavier García del Muro

  ICO- Hospitalet

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, open-label, single-arm

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 18, 2020
• Study Start: April 28, 2020
• Primary Completion: February 15, 2022
• Study Completion: August 26, 2022
• Last Updated: May 29, 2025
• Results First Posted: May 29, 2025

Record last verified: 2025-05

Locations

ES (10); IT (3)