JDB153 Combined With Penpulimab for Hepatocellular Carcinoma After Standard Treatment Failure

Official title

A Phase Ib/II Clinical Trial of JDB153 Combined With Penpulimab for the Treatment of Hepatocellular Carcinoma Refractory to Standard Therapy

Overview

The goal of this clinical trial is to evaluate the safety and efficacy of JDB153 combined with Penpulimab in patients with hepatocellular carcinoma after standard treatment failure.

Detailed description

This study is a single-arm, single-center, exploratory clinical trial aimed at evaluating the safety and efficacy of JDB153 combined with Penpulimab in patients with hepatocellular carcinoma after standard treatment failure.

Interventions

• Drug JDB153
  JDB153 is administered orally at doses of 600 mg twice daily (1200 mg total daily dose) or 500 mg twice daily (1000 mg total daily dose) based on safety and tolerability assessment.
• Drug Penpulimab
  Penpulimab is administered by intravenous infusion at a dose of 200 mg once every 3 weeks (Q3W).

Primary outcome measures

• Incidence of Treatment-Related Adverse Events [Time frame: Approximately 2 years]

Secondary outcome measures (6)

• Objective Response Rate (ORR) [Time frame: Approximately 2 years]
• Disease Control Rate (DCR) [Time frame: Approximately 2 years]
• Duration of Response (DoR) [Time frame: Approximately 2 years]
• Time to Progression (TTP) [Time frame: Approximately 2 years]
• Progression-Free Survival (PFS) [Time frame: Approximately 2 years]
• Overall Survival (OS) [Time frame: Approximately 2 years]

Eligibility criteria

Inclusion criteria

• Histologically or cytologically confirmed, or clinically diagnosed (according to Primary Liver Cancer 2024 guidelines or American Association for the Study of Liver Diseases \[AASLD\] hepatocellular carcinoma guidelines) locally advanced unresectable or metastatic hepatocellular carcinoma;
• Age 18-75 years, inclusive; no sex restrictions;
• Life expectancy ≥12 weeks;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Documented disease progression following prior standard systemic therapy. For patients who experienced disease progression within 6 months during or after adjuvant chemotherapy, the adjuvant chemotherapy will be considered first-line treatment;
• Presence of at least one measurable target lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Target lesions must have a maximum diameter of ≥1 cm if identified by helical computed tomography (CT) or ≥2 cm if identified by conventional CT or magnetic resonance imaging (MRI). All imaging must have been performed within 28 days prior to enrollment;
• Adequate bone marrow and organ function, as evidenced by laboratory test results obtained within 1 week prior to enrollment: Hemoglobin ≥90 g/L; Platelet count ≥75 × 10⁹/L; White blood cell count ≥3.0 × 10⁹/L; Absolute neutrophil count ≥1.5 × 10⁹/L; Total bilirubin ≤1.5 × upper limit of normal (ULN); Serum creatinine ≤1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 × ULN. Patients must not have received blood transfusions, granulocyte colony-stimulating factor (G-CSF), or other medical supportive treatments within 14 days prior to study drug administration;
• Child-Pugh score ≤7;
• Voluntary participation with provision of written informed consent.

Exclusion criteria

• History of other malignant tumors with disease-free survival <5 years (except cured basal cell carcinoma of the skin, cured cervical carcinoma in situ, and gastrointestinal tumors confirmed to be cured by endoscopic mucosal resection);
• Previous treatment with penpulimab;
• Presence of immunodeficiency disease or HIV infection;
• Severe, uncontrolled acute infection (defined as fever >38°C caused by infection); 5. History of active hepatitis B or active hepatitis C, defined as: HBV DNA titer ≥2000 IU/mL (or 1×10⁴ copies/mL) or HCV RNA ≥lower limit of detection; 6. Severe hepatic or renal dysfunction; or recent history of myocardial infarction (within 3 months); 7. Patients with active or previous autoimmune disease that has the potential for recurrence or poses associated risks (e.g., those who have undergone organ transplantation requiring immunosuppressive therapy). However, patients with Type I diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, or skin diseases not necessitating systemic treatment (e.g., vitiligo, psoriasis, or alopecia) are permitted to enroll; 8. History of interstitial lung disease or non-infectious pneumonitis that is symptomatic or has a history of pulmonary disease that may interfere with the detection or management of suspected drug-related pulmonary toxicity; 9. History of active tuberculosis infection within 1 year prior to first administration of study drug. However, for patients with a history of active tuberculosis infection more than 1 year ago, enrollment is considered appropriate if the investigator determines there is currently no evidence of active tuberculosis; 10. History of chronic diarrhea or presence of complete intestinal obstruction; 11. Patients requiring systemic treatment with corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days prior to administration of study drug. Note: Inhaled or topical steroids, or adrenal replacement therapy (≤10 mg/day prednisone equivalent), are permitted in the absence of active autoimmune disease. Short-term (≤7 days) use of corticosteroids for prophylactic treatment (e.g., contrast media allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reactions caused by contact allergens) is permitted; 12. Concurrent other serious medical or surgical conditions affecting organ function that the investigator considers inappropriate for participation in this clinical trial; 13. Participation in other investigational drug clinical trials within 4 weeks; 14. Pregnant or lactating women, or patients with reproductive potential (men or women who have been post-menopausal for less than 1 year) who are unwilling to use adequate contraceptive measures; 15. Patients with a history of allergic or hypersensitivity reactions to any study drug components; 16. Patients deemed inappropriate for participation in this clinical trial by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07075419 · JDB153-IIT-HCC001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗