Clinical Trials /

Efficacy of INCMGA00012 in Penile Squamous Cell Carcinoma (ORPHEUS)

NCT04231981

Description:

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

Related Conditions:
  • Squamous Cell Carcinoma of the Penis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy of INCMGA00012 in Penile Squamous Cell Carcinoma (ORPHEUS)
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: MedOPP239
  • NCT ID: NCT04231981

Conditions

  • Penile Cancer

Interventions

DrugSynonymsArms
INCMGA0012Interventional arm

Purpose

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

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).
    

Trial Arms

NameTypeDescriptionInterventions
Interventional armExperimentalPatients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
  • INCMGA0012

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Baseline up to 24 months
Safety Issue:
Description: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

Measure:Efficacy determined by Clinical Benefit Rate (CBR)
Time Frame:Baseline up to 24 months
Safety Issue:
Description: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.
Measure:Efficacy determined by Progression-free survival (PFS)
Time Frame:Baseline up to 24 months
Safety Issue:
Description: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.
Measure:Efficacy determined by 6-months PFS
Time Frame:Baseline up to 6 months
Safety Issue:
Description: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.
Measure:Efficacy determined by Duration of Response (DoR)
Time Frame:Baseline up to 24 months
Safety Issue:
Description: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.
Measure:Efficacy determined by Overall survival (OS)
Time Frame:Baseline up to 24 months
Safety Issue:
Description: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.
Measure:Efficacy determined by maximum tumor shrinkage
Time Frame:Baseline up to 24 months
Safety Issue:
Description: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.
Measure:Safety adverse events (AEs)
Time Frame:Baseline up to 24 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MedSIR

Trial 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

Last Updated

April 29, 2020