C43 Malignant melanoma of skin Malignant melanoma of skin
Conditions
Interventions
200 mg intravenous (IV) 3-weekly (Q3W) until unacceptable toxicity, disease recurrence, or a maximum of 18 cycles, or up to 1 year from randomization, whichever occurs first. - EU-approved Keytruda: 2
Sponsors
Celltrion, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Male or female =18 years 2.Subject has been newly diagnosed with histologically/pathologically confirmed Stage IIB, IIC, or III cutaneous melanoma per AJCC 8th edition staging system and then completely resected (including sentinel node if applicable) with documented negative margins (refer to Section 13.2 and Section 13.3). Note: Pathologic examination of surgical resection with wide excision on the primary lesion and sentinel lymph node biopsy (SLNB) and/or regional lymph node dissection on the regional lymph node are required for the study entry. 3.Final surgical resection within 12 weeks prior to the first study drug administration. Subject must have recovered adequately from surgery prior to the first study drug administration (refer to Section 13.3). 4.Eastern Cooperative Oncology Group performance status (ECOG PS) of =1 (refer to Section 8.4.2). 5.Subject must have adequate organ function as indicated by the following laboratory values based on the screening assessments within 14 days prior to the first study drug administration: a) White blood cell (WBC) counts = 2,000/uL b) Absolute neutrophil counts (ANC) = 1,500/uL c) Platelets = 100 x 1033 /uL d) Hemoglobin > 9.0 g/dL e) Measured or calculated creatinine clearance (CrCl) = 60 mL/min using the institutional standard formula for subjects with creatinine levels =1.5 x institutional upper limit of normal (ULN) (estimated glomerular filtration rate can be used in place of creatinine or CrCl) f) Aspartate Aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase [SGOT]) and Alanine Aminotransferase (ALT) (Serum Glutamate Pyruvate Transaminase [SGPT]) = 2.5 x ULN g) Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) h) International Normalized Ratio (INR) or Prothrombin Time and Activated Partial Thromboplastin Time (aPTT) = 1.5 x ULN unless a subject is receiving anticoagulant therapy as long as Prothrombin Time or aPTT is within therapeutic range of intended use of anticoagulants. 6. Subject and their partner of childbearing potential must agree to use acceptable birth control methods throughout the study and for 4 months after the last study drug administration. A man or woman is of childbearing potential if, in the opinion of the investigator, he or she is biologically capable of having children and is sexually active. Male and female subjects and their partners who have been surgically sterilized for less than 24 weeks prior to the date of informed consent must agree to use any medically acceptable methods of contraception. Menopausal females must have experienced their last period more than 1 year prior to the date of informed consent to be classified as not of childbearing potential (refer to Section 13.1). 7.Subject has the ability to comprehend the full nature and purpose of the study, including possible risks and side effects, to cooperate with the investigator, to understand verbal and/or written instructions, and to comply with the requirements of the entire study. 8. Subject and/or their legally authorized representative must be informed and given ample time and opportunity to read and/or understand the nature and purpose of this study and must sign the ICF before any study-specific procedures.
Exclusion criteria
Exclusion criteria: 1. Subject has one or more of the following medical conditions associated with melanoma: a) History of mucosal, uveal, or conjunctival melanoma b) History of a cutaneous/acral primary melanoma (excluding the culprit primary) within the preceding 5 year prior to the first study drug administration. Note: Subject with a history of nonulcerated cutaneous primary melanoma <0.8 mm in depth with no nodal involvement (i.e., Stage 0 or 1A nonulcerated cutaneous melanoma) are allowed in this study as long as all current disease has been resected. c) Past or current in-transit metastases or satellitosis d) Metastatic disease on imaging including brain metastases as determined by the investigator. Note: All suspicious lesions amenable to biopsy should be confirmed negative for malignancy before study entry. e) Any prior targeted, chemo, radio or immune therapy for melanoma except surgery for primary melanoma lesions 2. Subject has one or more of the following medical conditions: a) Any malignancy other than melanoma, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other in situ cancers, within 5 years prior to the first study drug administration b) Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first study drug administration c) History of non-infectious pneumonitis that required steroid or has current pneumonitis d) A current infection of hepatitis B, or a known history of infection with hepatitis C or human immunodeficiency virus (HIV). (refer to Section 8.4.5). Note: Subjects with a positive hepatitis C antibody test may be allowed in the study if hepatitis C RNA (ribonucleic acid) test is performed as per local practice and confirmed as negative. e) Active infection requiring systemic therapy within 2 weeks prior to the first study drug administration f) Active autoimmune disease that has required systemic treatment in past 2 years prior to the first study drug administration (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxin, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency [up to 5 mg/m22/ day prednisone equivalent with maximum dose of 10 mg daily]) is not considered a form of systemic treatment and is allowed. g) A history of a solid organ/tissue allogeneic transplant. h) Serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or the study drug administration, impair the ability of subject to receive protocol therapy, or interfere with the interpretation of study results. 3. Subject is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first study drug administration or 5 half-lives, whichever is longer 4. Subject has been previously exposed to anti-PD-1, -PD-L1, -PD-L2, Cytotoxic T-lymphocyte-associated antigen (CTLA), or any other antibody targeting T-cell costimulation or immune checkpoint pathway. Note: A subject treated with any monoclonal antibodies, other than those targeting T-cell costimulation or immune checkpoint pathway, may be allowed in the study if the treatment was completed earlier than
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUCtau at Cycle 1 in the PK – at Cycle 1 set AUCtau,SS at Cycle 7 in the PK – up to Cycle 7 set NAME OF THE RESULT: To demonstrate pharmacokinetic equivalence PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 21 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Occurrence and severity of TEAEs in the safety set Descriptive characterization of lab parameters and other safety evaluations in the safety set NAME OF THE RESULT: To evaluate safety profile PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 56 weeks ;AUCtau at Cycle 1 in the PK – at Cycle 1 set AUCtau,SS at Cycle 7 in the PK – up to Cycle 7 set NAME OF THE RESULT: To demonstrate pharmacokinetic equivalence PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 21 weeks ;Cmax, Cmin, Cav, degree of fluctuation [(Cmax-Cmin)/Cav], swing [(Cmax-Cmin)/Cmin], and Tmax at Cycle 1 in the PK – at Cycle 1 set; - Cmax, Cmin, Cav, degree of fluctuation [(Cmax-Cmin)/Cav], swing [(Cmax-Cmin)/Cmin], and Tmax at Cycle 7 in the PK - up to Cycle 7 set; - Ctrough at each cycle with PK sampling in the Safety set NAME OF THE RESULT: To assess additional PK parameters PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 56 weeks ;RFS, DMFS, and OS in the efficacy set NAME OF THE RESULT: To evaluate efficacy profile PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 56 weeks ;Incidence and titer levels of anti-pembrolizumab antibody and incidence of neutralizing antibody (if applicable) in the safety set NAME OF THE RESULT: To evaluate immunogenicity profile PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: 56 weeks | — |
Countries
Albania, Brazil, Georgia, Italy, Macedonia, Modalvia, Peru, Poland, Romania, Serbia, Slovenia, South Africa, Spain, Turkey, Ukraine
Contacts
Public ContactMilagros Patricia Navarrete
PPD PERU S.A.C.
Outcome results
None listed