SHR-1701 Plus Apatinib for Second-Line Treatment in Targeted-Immune Pretreated Advanced Hepatocellular Carcinoma

NCT07749859 | Not Yet Recruiting Phase 2

• 1 other identifier: 1701-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical study aims to evaluate the efficacy and safety of Retlirafusp alfa Injection (SHR-1701) combined with apatinib in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression after first-line targeted combined immunotherapy, and provide clinical evidence for the second-line treatment of advanced HCC. A total of 80 patients with radiologically or pathologically confirmed advanced/unresectable hepatocellular carcinoma with disease progression after prior first-line targeted-immunotherapy will be enrolled within 2.5 years. All enrolled patients will receive intravenous infusion of SHR-1701 at 30 mg/kg every 3 weeks in combination with oral apatinib 250 mg once daily; treatment will be maintained until disease progression or intolerable adverse toxicity occurs. The primary study endpoint is objective response rate (ORR).

Conditions

Advanced Unresectable Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma, SHR-1701, Apatinib, Second-line therapy

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  It is defined as the proportion of participants achieving complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or modified RECIST (mRECIST).

  From first dose until disease progression, death, or 24 months, whichever occurs first. Tumor response assessed every 6-9 weeks per RECIST v1.1.

Study Arms (1)

treatment group

EXPERIMENTAL

All enrolled subjects receive SHR-1701 plus apatinib for the treatment of second-line advanced hepatocellular carcinoma, and observe efficacy and safety indicators.

Drug: Retlirafusp alfa Injection, apatinib

Interventions

Retlirafusp alfa Injection, apatinib DRUG

All enrolled patients will receive intravenous infusion of SHR-1701 at 30 mg/kg every 3 weeks in combination with oral apatinib 250 mg once daily;TACE intervention is permitted during treatment, which can only be conducted after the first efficacy assessment. Treatment will be continued until disease progression, intolerable toxicity, or other treatment discontinuation criteria are met.

treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-75 years, male or female; signed informed consent form with good compliance;
• Patients with histologically confirmed hepatocellular carcinoma or meeting clinical diagnostic criteria, currently unresectable or metastatic;
• Prior receipt of first-line combined targeted and immunotherapy with subsequent disease progression or intolerance;
• At least one measurable lesion meeting the criteria of RECIST v1.1;
• ECOG performance status of 0 or 1;
• Expected survival ≥ 12 weeks;
• Child-Pugh Class A (score 5-6);
• Adequate organ and bone marrow function as defined below (tested within 14 days prior to initiation of study treatment):
• )Hematology laboratory values (no blood transfusion, granulocyte colony-stimulating factor \[G-CSF\], or corrective hematologic agents administered within 14 days before screening): A. Hemoglobin (Hb) ≥ 90 g/L; B. Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; C. Platelet count (PLT) ≥ 75 × 10⁹/L; 2)Serum chemistry laboratory values (no albumin transfusion within 14 days before screening): A. Total serum bilirubin (BIL) ≤ 2 × ULN (≤ 3 × ULN for patients with Gilbert syndrome); B. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN;
• C. For patients with liver metastases, ALT and AST ≤ 5 × ULN; serum creatinine (Cr) ≤ 1.5 × ULN OR endogenous creatinine clearance ≥ 50 mL/min (calculated via the Cockcroft-Gault formula):
• Male: Creatinine clearance = \[(140 - age) × body weight\] / (72 × serum Cr); Female: Creatinine clearance = \[(140 - age) × body weight\] / (72 × serum Cr) × 0.85(Body weight in kg; serum Cr in mg/dL) 9.Controllable proteinuria and blood pressure: urine protein \<2+ (or 24-hour urinary protein \<1.0 g, or urine protein/creatinine ratio \[UPC\] \<1.0); systolic blood pressure ≤140 mmHg and diastolic blood pressure ≤90 mmHg (achievable with antihypertensive medications); 10.Evaluation of portal hypertension and varices: esophagogastroduodenoscopy (EGD) performed within 6 months prior to enrollment; patients with medium-to-high risk esophageal and gastric varices must have completed prophylactic treatment per guidelines (e.g., endoscopic variceal ligation \[EVL\]/non-selective beta-blockers \[NSBB\]), and study treatment shall be initiated no earlier than 14 days after EVL; 11.Hepatitis B and C criteria: For subjects with positive HBsAg or HBcAb, HBV-DNA shall be below the lower limit of quantification, and nucleos(t)ide antiviral therapy shall be initiated and administered throughout the study period. Subjects with HCV infection shall have stable virological status (either receiving DAA therapy or previously cured); 12.Fertility requirements: Fertile subjects agree to use reliable contraception from enrollment until 6 months after the last study drug administration, with a negative pregnancy test prior to enrollment; 13.Recovery from prior therapies: All toxicities related to previous anti-tumor therapies have recovered to Grade 1 or baseline levels (except acceptable alopecia, stable hypoendocrine function, etc.). At least 3 weeks have elapsed since the last systemic anti-tumor therapy, at least 4 weeks since major surgery, and at least 4 weeks since local therapy (TACE, RFA, etc.) with stable recovery.

You may not qualify if:

• History of severe hypersensitivity or irreversible toxic reactions to similar PD-L1 agents or VEGFR-2 TKIs;
• Child-Pugh Class B or C, refractory ascites requiring paracentesis at least weekly, Grade ≥2 hepatic encephalopathy, or MELD score \>12 (optional, subject to institutional SOPs);
• High bleeding risk: Grade ≥3 gastrointestinal hemorrhage, perforation, active ulcer or uncontrolled bleeding diathesis within the past 6 months; untreated medium-to-large varices or high-risk signs identified on EGD without completed prophylactic intervention; clinical indication for potent anticoagulants or dual antiplatelet therapy that cannot be discontinued or substituted (aspirin ≤100 mg daily may be permitted at the Investigator's discretion);
• Prior treatment with apatinib or PD-L1 monoclonal antibody immune checkpoint inhibitors;
• Uncontrolled hypertension (persistent blood pressure ≥140/90 mmHg despite medical treatment), persistent proteinuria ≥2+ or uncorrected 24-hour urinary protein ≥1.0 g;
• Severe cardiovascular diseases: myocardial infarction (MI), unstable angina, NYHA Class III-IV heart failure, clinically significant arrhythmia, QTcF interval ≥470 ms within the preceding 6 months, or recent arterial/venous thromboembolic events;
• Recent surgical procedures or unhealed wounds: major surgery performed within 4 weeks prior to enrollment with unhealed incision; gastrointestinal perforation or fistula occurring within 6 months prior to enrollment;
• Active infections: bacterial or fungal infections requiring intravenous antibiotics, active tuberculosis; high HBV-DNA replication without antiviral therapy initiated; uncontrolled HIV infection (e.g., CD4 count \<200/μL or detectable viral load) or history of opportunistic infections;
• Active autoimmune disease or immunodeficiency requiring systemic immunosuppressive therapy (prednisone equivalent \>10 mg daily). The following subjects may be eligible: stable hypothyroidism on replacement therapy, type 1 diabetes mellitus, localized cutaneous vitiligo/psoriasis, and inflammatory bowel disease in remission without need for systemic immunosuppression (at the Investigator's discretion);
• Prior severe immune-related adverse events (irAEs ≥ Grade 3, such as severe pneumonitis, colitis, hepatitis, neuromuscular disorders, myocarditis, etc.) or recurrent irAEs requiring long-term immunosuppression.
• Symptomatic central nervous system metastases or metastases requiring glucocorticoid control; asymptomatic lesions stable for ≥4 weeks may be considered for enrollment (per institutional policy).
• History of other malignant tumors within the past 3 years, excluding cured basal/squamous cell skin carcinoma, cervical carcinoma in situ, or other cured low-risk malignancies.
• Pregnancy or breastfeeding; hypersensitivity to any component of the study drugs.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Langfang, Hebei, 065000, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

apatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Yongkun Sun, PhD

CONTACT

+86 10 87788800; hsunyk@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Deputy Director, Department of Medical Oncology

Study Record Dates

• First Submitted: August 3, 2026
• First Posted: August 6, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: August 6, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)