Advanced Unresectable Hepatocellular CarcinomaPhase 2NCT07749859
SHR-1701 Plus Apatinib for Second-Line Treatment in Targeted-Immune Pretreated Advanced Hepatocellular Carcinoma
A Phase 2 study testing Retlirafusp alfa Injection, apatinib in people with Advanced Unresectable Hepatocellular Carcinoma, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Unresectable Hepatocellular Carcinoma
- What is being tested?
- Retlirafusp alfa Injection, apatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteChina
- Study dates
- Aug 2026to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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):
- 1)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;
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Cancer Hospital Chinese Academy of Medical Sciences
Langfang, Hebei, 065000
Yongkun Sun, PhD, +86 10 87788800, hsunyk@126.com
About this study
Official title: An Exploratory Clinical Study of SHR-1701 Combined With Apatinib as Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Targeted and Immune Therapies
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).
Read the detailed description
This is a prospective, open-label, multicenter phase II clinical study. Eligible patients will receive combination therapy of SHR-1701 and apatinib with detailed administration regimens as follows:
SHR-1701: 30 mg/kg via intravenous infusion once every 3 weeks (Q3W); Apatinib: 250 mg taken orally once daily (QD). 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.
A safety lead-in phase is designed for this study: the first 6 subjects will be enrolled initially. Enrollment can proceed to recruit subsequent participants until a total of 80 eligible patients are enrolled if no more than 2 cases of dose-limiting toxicity (DLT) are observed within the lead-in phase. If 3 or more DLT events occur, subject enrollment will be suspended immediately, followed by a comprehensive safety assessment. The research team will decide to terminate the current dose cohort or adjust the dosage of study drugs for enrollment restart based on the assessment results.The whole study is expected to be completed within 3 years. Statistical analyses including interim and final analyses will be performed with SPSS or R software.
- Being tested
- Retlirafusp alfa Injection, apatinib
- Keywords
- Hepatocellular carcinoma, SHR-1701, Apatinib, Second-line therapy
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retlirafusp alfa Injection, apatinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Retlirafusp alfa Injection, apatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From first dose until disease progression, death, or 24 months, whichever occurs first. Tumor response assessed every 6-9 weeks per RECIST v1.1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2026
- Study startAug 2026 (estimated)
- Primary completionJul 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Unresectable Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, YONGKUN SUN, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07749859
- Sponsor's protocol ID
- 1701-01
- Status last verified
- Aug 2026
- First submitted
- 3 Aug 2026
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Study of SHR-1701 Combined With Apatinib as Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Targeted and Immune Therapies
- ClinicalTrials.gov ID
- NCT07749859
- Acronym / sponsor ID
- 1701-01
- Keywords
- Hepatocellular carcinoma, SHR-1701, Apatinib, Second-line therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- Aug 2026 (estimated)
- Primary completion
- Jul 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 6 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
This is a prospective, open-label, multicenter phase II clinical study. Eligible patients will receive combination therapy of SHR-1701 and apatinib with detailed administration regimens as follows:
SHR-1701: 30 mg/kg via intravenous infusion once every 3 weeks (Q3W); Apatinib: 250 mg taken orally once daily (QD). 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.
A safety lead-in phase is designed for this study: the first 6 subjects will be enrolled initially. Enrollment can proceed to recruit subsequent participants until a total of 80 eligible patients are enrolled if no more than 2 cases of dose-limiting toxicity (DLT) are observed within the lead-in phase. If 3 or more DLT events occur, subject enrollment will be suspended immediately, followed by a comprehensive safety assessment. The research team will decide to terminate the current dose cohort or adjust the dosage of study drugs for enrollment restart based on the assessment results.The whole study is expected to be completed within 3 years. Statistical analyses including interim and final analyses will be performed with SPSS or R software.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| treatment group | Experimental | Drug: Retlirafusp alfa Injection, apatinibAll enrolled subjects receive SHR-1701 plus apatinib for the treatment of second-line advanced hepatocellular carcinoma, and observe efficacy and safety indicators. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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;
Key exclusion criteria (13 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Retlirafusp alfa Injection, apatinibAll 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. | Drug | treatment group |
Primary outcome
Objective Response Rate (ORR)
Time frame: From first dose until disease progression, death, or 24 months, whichever occurs first. Tumor response assessed every 6-9 weeks per RECIST v1.1.
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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Retlirafusp alfa Injection, apatinib in people with Advanced Unresectable Hepatocellular Carcinoma, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yongkun Sun, PhD (+86 10 87788800, hsunyk@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: From first dose until disease progression, death, or 24 months, whichever occurs first. Tumor response assessed every 6-9 weeks per RECIST v1.1.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2026.