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Keytruda Pantumor
Keytruda Pantumor

ORPHEUS Efficacy of INCMGA00012 in Penile Squamous Cell Carcinoma (ORPHEUS)



April 2020

Letztes Update:


Indikation (Clinical Trials):
Carcinoma, Carcinoma, Squamous Cell, Penile Neoplasms


Erwachsene (18+)

Phase 2


Incyte Corporation


Xavier García del Muro
Principal Investigator
ICO- Hospitalet


Studienlocations (3 von 12)

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
ItalyNoch nicht rekrutierend» Google-Maps
Hospital de la Santa Creu i Sant Pau
SpainRekrutierend» Google-Maps
Hospital Universitari Son Espases
Palma De Mallorca
SpainRekrutierend» Google-Maps
Hospital Insular de Gran Canaria
Palmas de Gran Canaria
SpainRekrutierend» Google-Maps
Alle anzeigen


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



Inclusion Criteria:

1. 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.

2. Male patients ≥ 18 years of age at the time of signing ICF.

3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1.

4. Life expectancy ≥12 weeks.

5. Histologically-proven PSqCC.

6. Locally advanced unresectable or metastatic stage 4 PSqCC that is not amenable to

resection with curative intent (T4 or N3 or M1).

7. Radiological evidence of locally advanced or metastatic disease.

8. Patients must have measurable disease or evaluable disease according to Response

Evaluation Criteria in Solid Tumors (RECIST) version (v.)1.1 criteria.

9. 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).

10. 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.

11. Adequate organ function:

1. 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


2. 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.

3. 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).

4. 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.

12. Patients who are willing and able to comply with scheduled visits, treatment plan,

laboratory tests, and other study procedures.

13. 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.

14. 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.

15. For pretreated patients, last dose of chemotherapy administered ≥ 28 days from study


Exclusion criteria

1. Locally PSqCC candidate for curative treatment.

2. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

3. Known hypersensitivity to any of the excipients of INCMGA00012.

4. 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.

5. Radiotherapy within 14 days of first dose of study treatment with the following

caveat: 28 days for pelvic radiotherapy.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. Diagnosis of immunodeficiency or is receiving systemic steroid therapy or

immunosuppressive therapy within seven days prior to study treatment initiation.

12. 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.

13. Prior allogenic stem cell or solid organ transplantation.

14. 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.

15. Active/history of pneumonitis requiring treatment with steroids or active/history of

interstitial lung disease.

16. Active uncontrolled infection at the time of screening.

17. Latent tuberculosis determined by a positive TST followed by confirmation by


18. Participants who are known to be human immunodeficiency virus (HIV)-positive, unless

all of the following criteria are met:

1. CD4-positive count ≥ 300/μL;

2. Undetectable viral load;

3. Receiving highly active antiretroviral therapy.

19. 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


20. 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.

21. 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.


Primary outcome:

1. Objective response rate (ORR) (Time Frame - Baseline up to 24 months):
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.

Secondary outcome:

1. Efficacy determined by Clinical Benefit Rate (CBR) (Time Frame - Baseline up to 24 months):
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.

2. Efficacy determined by Progression-free survival (PFS) (Time Frame - Baseline up to 24 months):
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.

3. Efficacy determined by 6-months PFS (Time Frame - Baseline up to 6 months):
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.

4. Efficacy determined by Duration of Response (DoR) (Time Frame - Baseline up to 24 months):
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.

5. Efficacy determined by Overall survival (OS) (Time Frame - Baseline up to 24 months):
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.

6. Efficacy determined by maximum tumor shrinkage (Time Frame - Baseline up to 24 months):
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.

7. Safety adverse events (AEs) (Time Frame - Baseline up to 24 months):
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.

Geprüfte Regime

  • INCMGA0012:
    INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.


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