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Penile CancerPhase 2ORPHEUSNCT04231981

Efficacy of INCMGA00012 in Penile Squamous Cell Carcinoma (ORPHEUS)

A Phase 2 study testing Retifanlimab in people with Penile Cancer, run by MedSIR at 13 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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 Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Penile Cancer
What is being tested?
Retifanlimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
13 sitesin 2 countries
Study dates
28 Apr 2020to 26 Aug 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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).
  • Willingness and ability to provide blood samples (liquid biopsy) at the time of inclusion, after 2 cycles of study treatment (C3D1), and upon PD or study termination.
  • 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.
  • Subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 180 days after the last dose of study treatment.
  • Patients that have received prior chemotherapy regimens or radiotherapy for locally recurrent and/or metastatic disease are not excluded but patients naïve of systemic treatment can also be included.
  • For pretreated patients, last dose of chemotherapy administered ≥ 28 days from study entry.

Who cannot join

  • 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.
  • Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline (with the exception of any grade of alopecia and anemia not requiring transfusion support). Endocrinopathy, if well-managed, is not exclusionary and should be discussed with Sponsor's medical monitor.
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  • 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.
  • Active uncontrolled infection at the time of screening.
  • Latent tuberculosis determined by a positive TST followed by confirmation by pulmonologists.
  • Participants who are known to be human immunodeficiency virus (HIV)-positive, unless all of the following criteria are met:
  • CD4-positive count ≥ 300/μL;
  • Undetectable viral load;
  • Receiving highly active antiretroviral therapy.
  • Active hepatitis A virus (HAV) (positivity for HAV IgM antibody), hepatitis B virus (HBV) (patients with negative hepatitis B surface antigen [HBsAg] test and a positive antibody to HBsAg [anti-HBsAg] test at screening are eligible) or hepatitis C virus (HCV) (patients with a positive antibody to hepatitis C [anti-HCV] are eligible only if polymerase chain reaction [PCR] is negative for virus hepatitis C ribonucleic acid [RNA]).
  • Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for >1 year, after treatment with curative intent.
  • Patients have any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment contraindicate patient participation in the clinical study.

Trial locations and contacts

13 sites in 2 countries.

13 sites in 2 countries

Spain10 sites

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • ICO-Hospitalet

    L'Hospitalet de Llobregat

  • Hospital Insular de Gran Canaria

    Las Palmas de Gran Canaria

  • Hospital 12 de octubre

    Madrid

  • Hospital Clínico San Carlos

    Madrid

  • Hospital Virgen de la Arrixaca

    Murcia

  • Hospital Universitari Son Espases

    Palma de Mallorca

  • Hospital Virgen del Rocío

    Seville

  • Instituto Valenciano de Oncología

    Valencia

  • Hospital Miguel Servet

    Zaragoza

Other trials in Spain

Italy3 sites

  • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.

    Milan

  • IRCCS Ospedale San Raffaele

    Milan, 20132

  • AUSL Reggio Emilia

    Reggio Emilia

Other trials in Italy

About this study

Official title: A Multicenter, Open-Label, Single-Arm, Phase II Clinical Trial to Evaluate the Efficacy and Safety of INCMGA00012 in Advanced Penile Squamous Cell Carcinoma.

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

Read the detailed description

Men age ≥ 18 years with locally advanced unresectable or metastatic PSqCC stage 4 (i.e. T4 or N3 or M1) that are presenting with radiologic progression of disease (PD) following or not standard treatment with chemotherapy.

After signing the ICF and confirmed eligibility, patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle, once every four weeks for up to 2 years.

Patients will receive treatment until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.

Patients discontinuing the study treatment period will enter a post-treatment follow-up period during which survival and new anti-cancer therapy information will be collected every 3 months (± 14 days) from the last dose of investigational product until the end of study (EoS).

Conditions
Penile Cancer
Being tested
Retifanlimab
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
Medical subject headings
Penile Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RetifanlimabDrug

    Also called INCMGA0012

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

Study groups in NCT04231981
Study groupRoleWhat they receive
Interventional armExperimentalPatients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Receives: Drug: Retifanlimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (7)

  1. Efficacy Determined by Clinical Benefit Rate (CBR)

    CBR is defined as the number of patients with CR, partial response (PR) or stable disease (SD) (for at least 12 weeks) divided by the number of patients in the analysis set.

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

  2. Efficacy Determined by Progression-free Survival (PFS)

    PFS is defined as the time from the date of the first dose of study treatment until the first documented PD based on RECIST v1.1. or death due to any cause, whichever occurs first based on local investigator's assessment according to RECIST criteria v1.1.

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

  3. Efficacy Determined by 6-months PFS

    6-months PFS rate is defined as the proportion of patients who are alive and progression-free at 6 months from the date of first dose of study treatment based on iRECIST criteria.

    Measured: Baseline up to 6 months

  4. Efficacy Determined by Duration of Response (DoR)

    DoR is defined as the time from first documented CR or PR until disease progression or death from any cause, based on local investigator's assessment according to RECIST criteria v1.1.

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

  5. Efficacy Determined by Overall Survival (OS)

    OS is defined as the time from the date of first dose of study treatment until death by any cause or the last date the patient was known to be alive.

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

  6. Efficacy Determined by Maximum Tumor Shrinkage

    Maximum tumor shrinkage is defined as the percentage of tumor shrinkage from baseline (obtained from the sum of largest diameters of the target lesions), based on local investigator's assessment according to RECIST criteria v1.1.

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

  7. Safety Adverse Events (AEs)

    Number of patients with treatment-related AEs (Grade 3 and 4 AEs and serious adverse events [SAEs]) by using the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study start28 Apr 2020
  3. Primary completion15 Feb 2022
  4. Study completion26 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Multicenter, open-label, single-arm
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04231981
Sponsor's protocol ID
MedOPP239
Other IDs
2019-001172-11, 2019
Acronym
ORPHEUS
Status last verified
May 2025
First submitted
9 Jan 2020
Last updated
29 May 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Retifanlimab in people with Penile Cancer, run by MedSIR at 13 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Spain, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: From baseline until disease progression or treatment discontinuation, up to 10.3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04231981.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2025; AzTrials last refreshed its copy on 8 Nov 2026.

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