Efficacy of INCMGA00012 in Penile Squamous Cell Carcinoma (ORPHEUS)

Inclusion Criteria

• 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).
• 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) ( 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.

Exclusion criteria

• 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.
• 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