advanced stage hepatocellular carcinoma MedDRA version: 21.1 Level: PT Classification code 10073069 Term: Hepatic cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
O
MK-7902
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENVATINIB MESILATE
CAS Number: 857890-39-2
Other descriptive name: MK-7902
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of HCC. 2. Have a tumor, not eligible for resection or local ablation. 3. Have experienced disease progression under previous = 4 cycles/12 weeks first line IO-based therapy. 4. Have a Child-Pugh Classification score = 6 for assessed liver function within 7 days before allocation 5. Have at least one measurable site of disease based on RECIST 1.1 with spiral CT scan or MRI. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 6. Male/female* participants who are at least 18 years of age on the day of signing informed consent will be enrolled in this study. *There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently. 7. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. A male participant with female partner of childbearing potential is eligible to participate if he agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. 8. A male participant must agree to use a contraception as detailed in this protocol during the treatment period and for at least 210 days after the last dose of study treatment and refrain from donating sperm during this period. 9. The participant provides written informed consent for the trial. 10. Either pre-treatment tumor tissue available OR tumor tissue is not available as e.g., patient has never undergone biopsy or tissue depleted because of prior diagnostic testing 11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of allocation. 12. Have a life expectancy of = 12 weeks. 13. Have adequate organ function as defined in the following table (Table 2). Specimens must be collected within 7 days prior to the start of study intervention. Table 2: Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) = 1500/µL Platelets = 75000/µL Hemoglobin = 8.0 g/dLa Renal Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) = 1.5 × ULN OR = 40 mL/min for participant with creatinine levels > 1.5 × institutional ULN Hepatic Total bilirubin = 2 mg/dL OR direct bilirubin = ULN for participants with total bilirubin levels > 2 mg/dL AST (SGOT) and ALT (SGPT) = 5 × ULN Albumin = 3.0 g/dL Pancreatic Amylase = 1.5 × ULN Lipase = 1.5 × ULN Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) = 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. a Transfusion are permitted to meet criteria. b Creatinine clearance (CrCl) should be calculated per institutional standard. Note: This tabl
Exclusion criteria
Exclusion criteria: 1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. 2. Have received prior therapy with any TKI. 3. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 4. Have an ongoing AE (=Grade 2) from prior systemic anti-cancer therapy including investigational agents or use of an investigational device. 5. Have received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (= 2 weeks of radiotherapy) to non-CNS disease. 6. Have received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. 7. Are currently participating in a study of an investigational agent or an investigational device. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as they have recovered from all AEs due to previous therapies to = Grade 1 or baseline. Participants with = Grade 2 neuropathy may be eligible. 8. Have a diagnosis of immunodeficiency or are 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 dose of study drug. 9. Have a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 10. Have known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 11. Have severe hypersensitivity (= Grade 3) to lenvatinib, pembrolizumab and/or any of its excipients. 12. Have a history of congestive heart failure NYHA > Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study treatment, or cardiac arrhythmia requiring medical treatment at Screening 13. Have bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. Note: The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy. 14. Have active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed. 15. Have a history of (non-infectious) pneumonitis/interstitial lung disease that requir
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression free survival (PFS) Overall survival (OS) Safety and Toxcitiy;Timepoint(s) of evaluation of this end point: End of Study | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to assess the efficacy by Objective response rate (ORR) according to RECIST 1.1 criteria of the combined treatment with pembrolizumab and lenvatinib;Secondary Objective: Secondary objectives of this study are to assess the efficacy by progression free survival and by overall survival as well as to assess safety and toxicity of the combined treatment with pembrolizumab and lenvatinib;Primary end point(s): Objective response rate (ORR) – percentage of patients with complete response (CR) or partial response (PR) according to RECIST 1.1.;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Germany
Contacts
Public ContactIKF
Frankfurter Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Outcome results
None listed