Sequential PD-1/PD-L1 Inhibitor and LENvatinib in TLCT and Refractory Hepatoblastoma After Chemotherapy

Sequential PD-1/PD-L1 Inhibitor and LENvatinib in Transitional Liver Cell Tumors（TLCT）and Refractory Hepatoblastoma for Young Adolescent and Pediatric Participants After Chemotherapy：a Cohort Study

This is a single arm, open-label trial studying the combination of PD-1/PD-L1 Inhibitor (e.g.pembrolizumab, Sintilimab,Duvarizumab，Camrelizumab )and lenvatinib given at the recommended dose in pediatric and young adolescent patients((5 year-old<age<14 year-old) with TLCT or refractory hepatoblastoma after chemotherapy.

Transitional liver cell tumors exhibit an unusual phenotype with respect to clinical presentation, histopathology, immunohistochemistry, and treatment response. These apparently novel, unusual, and aggressive tumors occurring in older children and adolescents may form a transition in the putative developmental pathway of hepatocarcinogenesis, and usually refractory, resistant to chemotherapy.

The sPLENTY-pc is a perspective cohort study, investigating the efficiency of sequential combined usage of PD-1 Inhibitor (e.g.pembrolizumab, Sintilimab,Camrelizumab ) or PD-L1 inhibitor (Duvarizumab) plus lenvatinib given at the recommended dose in pediatric >5 year-old and young adult patients<14 yo with TLCT or refractory hepatoblastoma after chemotherapy.

Inclusion Criteria:

• Patients must be >= than 5 years and =< 14 years of age at the time of study enrollment
• pathological diagnosis of TLCT/NOS, or hepatoblastoma（HB）（Emergent Treatment for HB In emergency situation when a patient meets all other eligibility criteria and has had baseline required observations, but is too ill to undergo a biopsy safely, the patient may be enrolled without a biopsy.）
• Failed prior first-line or second-line chemotherapy
• general charactoristics: Lansky performance status 50-100% in patients ≤ 10 years of age OR Karnofsky performance status 50-100% in patients > 10 years of age Life expectancy > 8 weeks Hemoglobin > 8 g/dL Absolute neutrophil count > 1,000/mm^3 Platelet count > 100,000/mm^3 Total bilirubin ≤ 5 x upper limit of normal (ULN) for age, Aspartate aminotransferase (AST) or Alanine transaminase (ALT) < 10 x upper limit of normal (ULN) for age. Serum creatinine ≤ 3 times normal Normal metabolic parameters (i.e., serum electrolytes, glucose, calcium, and phosphate) Not pregnant or nursing No severe uncontrolled infection or enterocolitis
• Recovered from toxicity of prior therapy No chemotherapy within 3 weeks prior to study entry No prior PD1/PD-L1 blockade treatment

Exclusion Criteria:

• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
• Patients who are currently receiving another investigational drug.
• Patients who are currently receiving other anticancer agents.
• Patients with uncontrolled infection.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of PD1/PD-L1 blockade