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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04231981
Recruitment Status : Active, not recruiting
First Posted : January 18, 2020
Last Update Posted : August 27, 2021
Incyte Corporation
Information provided by (Responsible Party):

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

Condition or disease Intervention/treatment Phase
Penile Cancer Drug: INCMGA0012 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Multicenter, open-label, single-arm
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : April 28, 2020
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Interventional arm
Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Drug: INCMGA0012
INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.

Primary Outcome Measures :
  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 Measures :
  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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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 g/dL.
    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 entry.

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 pulmonologists.
  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 [RNA]).
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04231981

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IRCCS Ospedale San Raffaele
Milano, Italy, 20132
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
Milan, Italy
AUSL Reggio Emilia
Reggio Emilia, Italy
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospitalet de Llobregat, Spain
Hospital 12 de octubre
Madrid, Spain
Hospital Clínico San Carlos
Madrid, Spain
Hospital Virgen de la Arrixaca
Murcia, Spain
Hospital Universitari Son Espases
Palma De Mallorca, Spain
Hospital Insular de Gran Canaria
Palmas de Gran Canaria, Spain
Hospital Virgen del Rocío
Sevilla, Spain
Instituto Valenciano de Oncología
Valencia, Spain
Hospital Miguel Servet
Zaragoza, Spain
Sponsors and Collaborators
Incyte Corporation
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Principal Investigator: Xavier García del Muro ICO- Hospitalet
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Responsible Party: MedSIR Identifier: NCT04231981    
Other Study ID Numbers: MedOPP239
2019-001172-11 ( EudraCT Number )
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: August 27, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MedSIR:
Penile Cancer
Penile squamous cell carcinoma
Locally advanced penile cancer
Metastatic penile cancer
Unresectable locally advanced penile cancer
Unresectable penile cancer
Penile Cancer stage IV
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Penile Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Penile Diseases