Intrahepatic Cholangiocarcinoma (Icc)Phase 2H-FROGNCT07847710
Perioperative Retlirafusp Alfa(Anti-PD-L1/TGF-β Bifunctional Fusion Protein) Plus Famitinib and GEMOX-Based Hepatic Arterial Infusion Chemotherapy for Locally Advanced Intrahepatic Cholangiocarcinoma: A Multicenter, Single-Arm, Exploratory Phase II Trial
A Phase 2 study testing Retlirafusp alfa, Famitinib malate and Gemcitabine & oxaliplatin in people with Intrahepatic Cholangiocarcinoma (Icc) and Neoadjuvant Therapy, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This is a multicenter, single-arm, exploratory clinical study for adults with locally advanced intrahepatic cholangiocarcinoma (ICC) that may be technically resectable but is difficult to remove directly by surgery. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Intrahepatic Cholangiocarcinoma (Icc), Neoadjuvant Therapy
- What is being tested?
- Retlirafusp alfa, Famitinib malate and Gemcitabine & oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteChina
- Study dates
- 30 Sep 2026to 1 Mar 2029
- Phase
- Phase 2
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
- Participants must meet all of the following criteria:
- Voluntarily agree to participate in the study and sign the informed consent form.
- Age 18 to 75 years at the time of signing informed consent, male or female.
- Histologically and/or cytologically confirmed intrahepatic cholangiocarcinoma.
- ECOG performance status of 0 to 1.
- No prior systemic therapy or tumor-related surgery, except biliary drainage.
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- No extrahepatic metastasis.
- Considered technically resectable by an experienced hepatobiliary surgeon.
- At least one measurable lesion according to RECIST 1.1.
- Adequate organ and bone marrow function, as defined by the protocol.
- Women of childbearing potential must have a negative serum pregnancy test within 7 days before treatment and agree to use effective contraception during the study and for 1 year after the last study treatment. Male participants with partners of childbearing potential must also agree to use effective contraception during the study and for 1 year after the last study treatment.
- Life expectancy of at least 12 weeks.
Who cannot join
- Participants meeting any of the following criteria will be excluded:
- Pathological diagnosis of hepatocellular carcinoma, mixed liver cancer, or other non-cholangiocarcinoma malignant tumor components.
- Prior systemic therapy or other tumor-related treatment, except biliary drainage.
- Diagnosis of any other malignancy within 5 years before the first study treatment, except cured localized tumors such as cervical carcinoma in situ, basal cell carcinoma of the skin, or low-grade prostate cancer.
- Known uncontrolled pulmonary fibrosis, interstitial lung disease, or acute lung disease.
- Participation in another clinical trial of an investigational drug or device within 4 weeks before the first study treatment.
- Active hepatitis B or hepatitis C infection.
- Active autoimmune disease requiring systemic treatment within 2 years before the first
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, 1 recruiting
- Recruiting
The First Affiliated Hospital with Nanjing Medical University
Nanjing, Jiangsu, 210029
Jianhua Rao Professor Rao, Ph.D., +86 18262637266, raojh@njmu.edu.cn
About this study
Official title: Perioperative Retlirafusp Alfa（Anti-PD-L1/TGF-β Bifunctional Fusion Protein） Plus Famitinib and GEMOX-Based Hepatic Arterial Infusion Chemotherapy for Locally Advanced Intrahepatic Cholangiocarcinoma: A Multicenter, Single-Arm, Exploratory Phase II Trial: H-FROG Feasibility Study
This is a multicenter, single-arm, exploratory clinical study for adults with locally advanced intrahepatic cholangiocarcinoma (ICC) that may be technically resectable but is difficult to remove directly by surgery. The study will evaluate whether perioperative treatment with Retlirafusp alfa, famitinib malate, and hepatic arterial infusion chemotherapy using gemcitabine and oxaliplatin (HAIC-GEMOX) can help control the tumor before surgery and support further treatment after surgery.
Participants who meet the study requirements will receive neoadjuvant treatment before surgery. After surgery, participants will receive adjuvant treatment with Retlirafusp alfa combined with capecitabine or S-1. The study treatment and follow-up will continue until disease progression, unacceptable side effects, death, withdrawal of consent, or other protocol-defined stopping criteria.
The main purpose of the study is to evaluate event-free survival. The study will also monitor tumor response, surgery-related outcomes, survival, and safety. Participants will have regular safety visits, blood tests, imaging examinations, and follow-up visits during and after treatment.
- Being tested
- Retlirafusp alfa, Famitinib malate, Gemcitabine & oxaliplatin, Capecitabine, S-1
- Keywords
- Intrahepatic cholangiocarcinom, neoadjuvant therapy
- Medical subject headings
- Cholangiocarcinoma, Cirrhosis, Familial, with Pulmonary Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Retlirafusp alfaDrug
Also called shr-1701
30 mg/kg, i.v., q3w, Day 3 of each 3-week cycle.
Famitinib malateDrug
Also called Famitinib
10 mg, orally, once daily.
Gemcitabine & oxaliplatinDrug
Also called GEMOX
hepatic arterial infusion, Day 1 of each 3-week cycle.
CapecitabineDrug
1250 mg/m², orally twice daily, Days 1-14 of each 3-week cycle, as postoperative adjuvant therapy.
S-1Drug
40 mg/m², orally twice daily, Days 1-28 of each 6-week cycle, as postoperative adjuvant therapy.
hepatic arterial infusion chemotherapy (HAIC)Procedure or surgery
Hepatic arterial infusion chemotherapy with gemcitabine and oxaliplatin administered on Day 1 of each 3-week cycle.
| Study group | Role | What they receive |
|---|---|---|
| Combined treatment group | Experimental | Participants in this single arm will receive perioperative treatment with rilvegostomig alpha, famitinib malate, and HAIC-GEMOX before surgery, followed by postoperative adjuvant therapy with rilvegostomig alpha plus capecitabine or S-1 when applicable. Receives: Drug: Retlirafusp alfa; Drug: Famitinib malate; Drug: Gemcitabine & oxaliplatin; Drug: Capecitabine; Drug: S-1; Procedure: hepatic arterial infusion chemotherapy (HAIC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
EFS is defined as the time from the start of treatment to the first occurrence of any event, including disease progression that precludes surgery, local or distant recurrence, or death from any cause.
Measured: From the start of treatment until the first EFS event, assessed up to 36 months.
Secondary outcomes (6)
Pathological complete response rate
Percentage of participants who achieve pathological complete response after neoadjuvant treatment and surgery.
Measured: At the time of surgical pathological assessment, assessed up to 36 months.
Major pathological response rate
Percentage of participants who achieve major pathological response. Major pathological response is defined as residual viable tumor cells accounting for 50% or less of the tumor bed.
Measured: At the time of surgical pathological assessment, assessed up to 36 months.
R0 resection rate
Percentage of participants who undergo R0 resection, defined as no gross residual tumor and no tumor cells within 1 mm of the microscopic surgical margin.
Measured: At the time of surgery, assessed up to 36 months.
Disease-free survival
DFS is defined as the time from the date of surgery to disease recurrence or death from any cause.
Measured: From the date of surgery until recurrence or death, assessed up to 36 months.
Overall survival
OS is defined as the time from the start of neoadjuvant treatment to death from any cause or the date of last follow-up.
Measured: From the start of neoadjuvant treatment until death or last follow-up, assessed up to 36 months.
Incidence and severity of adverse events
Safety will be assessed by the incidence and severity of adverse events and serious adverse events according to NCI-CTCAE v5.0, as well as changes in vital signs, laboratory test results, and quality-of-life scores.
Measured: From the start of treatment through the safety follow-up period, assessed up to 36 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2026
- Study start30 Sep 2026
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intrahepatic Cholangiocarcinoma (Icc)Studies of the same condition, open and under way.
- 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
- 81 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Feng Cheng, MD, Study director, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07847710
- Sponsor's protocol ID
- H-FROG
- Acronym
- H-FROG
- Status last verified
- Sep 2026
- First submitted
- 23 Sep 2026
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided