Penile Cancer
Conditions
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
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
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).
Interventions
DRUGRetifanlimab
INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years.
Sponsors
Incyte Biosciences International Sàrl
MedSIR
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multicenter, open-label, single-arm
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From baseline until disease progression or treatment discontinuation, up to 10.3 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
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Determined by Progression-free Survival (PFS) | From baseline until disease progression or treatment discontinuation, up to 10.3 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. |
| Efficacy Determined by 6-months PFS | 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. |
| Efficacy Determined by Duration of Response (DoR) | From baseline until disease progression or treatment discontinuation, up to 10.3 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. |
| Efficacy Determined by Clinical Benefit Rate (CBR) | From baseline until disease progression or treatment discontinuation, up to 10.3 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. |
| Efficacy Determined by Maximum Tumor Shrinkage | From baseline until disease progression or treatment discontinuation, up to 10.3 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. |
| Safety Adverse Events (AEs) | From baseline until disease progression or treatment discontinuation, up to 10.3 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. |
| Efficacy Determined by Overall Survival (OS) | From baseline until disease progression or treatment discontinuation, up to 10.3 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. |
Countries
Italy, Spain
Participant flow
Recruitment details
Between April 2020 and August 2021, a total of 18 male patients with locally advanced unresectable or metastatic PSqCC stage 4 (i.e. T4 or N3 or M1)presenting radiologic PD and/or chemotherapy were enrolled at 9 sites. Due there's only one arm, all the patients received INCMGA00012 until disease progression, death or discontinuation from the study.
Pre-assignment details
Male patients ≥ 18 years of age. ECOG Performance Status ≤ 1. Life expectancy ≥12 weeks. Histologically-proven PSqCC. Locally advanced unresectable/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. - Adequate organ function.
Participants by arm
| Arm | Count |
|---|---|
| Interventional Arm Patients will receive INCMGA00012 500 mg by intravenous infusion on Day1 of each cycle.
Retifanlimab: INCMGA00012 500 mg will be administered on Day1 of each cycle (once every four weeks), for up to 2 years. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 16 |
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Interventional Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 66.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment Italy | 5 participants |
| Region of Enrollment Spain | 13 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 18 |
| other Total, other adverse events | 5 / 18 |
| serious Total, serious adverse events | 5 / 18 |
Outcome results
Primary
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.
Time frame: From baseline until disease progression or treatment discontinuation, up to 10.3 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Interventional Arm | Objective Response Rate (ORR) | Yes | 3 Participants |
| Interventional Arm | Objective Response Rate (ORR) | No | 15 Participants |
Secondary
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.
Time frame: Baseline up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Interventional Arm | Efficacy Determined by 6-months PFS | 2 Participants |
Secondary
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.
Time frame: From baseline until disease progression or treatment discontinuation, up to 10.3 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Interventional Arm | Efficacy Determined by Clinical Benefit Rate (CBR) | Yes | 4 Participants |
| Interventional Arm | Efficacy Determined by Clinical Benefit Rate (CBR) | No | 14 Participants |
Secondary
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.
Time frame: From baseline until disease progression or treatment discontinuation, up to 10.3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Interventional Arm | Efficacy Determined by Duration of Response (DoR) | 3.3 months |
Secondary
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.
Time frame: From baseline until disease progression or treatment discontinuation, up to 10.3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Interventional Arm | Efficacy Determined by Maximum Tumor Shrinkage | 15.9 percentage of change from baseline | Standard Deviation 49.1 |
Secondary
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.
Time frame: From baseline until disease progression or treatment discontinuation, up to 10.3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Interventional Arm | Efficacy Determined by Overall Survival (OS) | 17 Participants |
Secondary
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.
Time frame: From baseline until disease progression or treatment discontinuation, up to 10.3 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Interventional Arm | Efficacy Determined by Progression-free Survival (PFS) | 2 months |
Secondary
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.
Time frame: From baseline until disease progression or treatment discontinuation, up to 10.3 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Interventional Arm | Safety Adverse Events (AEs) | Related AEs | 5 Participants |
| Interventional Arm | Safety Adverse Events (AEs) | Related SAEs | 0 Participants |
| Interventional Arm | Safety Adverse Events (AEs) | Related Grade 3 or 4 AEs | 1 Participants |
| Interventional Arm | Safety Adverse Events (AEs) | Safe patients from related AEs | 12 Participants |