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

NCT07847710 | Recruiting Phase 2

• 1 other identifier: H-FROG
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Intrahepatic Cholangiocarcinoma (Icc); Neoadjuvant Therapy

Keywords

Intrahepatic cholangiocarcinom; neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  From the start of treatment until the first EFS event, assessed up to 36 months.

Secondary Outcomes (6)

• Pathological complete response rate

  At the time of surgical pathological assessment, assessed up to 36 months.

• Major pathological response rate

  At the time of surgical pathological assessment, assessed up to 36 months.

• R0 resection rate

  At the time of surgery, assessed up to 36 months.

• Disease-free survival

  From the date of surgery until recurrence or death, assessed up to 36 months.

• Overall survival

  From the start of neoadjuvant treatment until death or last follow-up, assessed up to 36 months.

Study Arms (1)

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.

Drug: Rilvegostomig Alpha; Drug: Famitinib malate; Drug: Gemcitabine & oxaliplatin; Drug: Capecitabine; Drug: S-1; Procedure: hepatic arterial infusion chemotherapy (HAIC)

Interventions

Rilvegostomig Alpha DRUG

30 mg/kg, i.v., q3w, Day 1 of each 3-week cycle.

Also known as: shr-1701

Combined treatment group

Famitinib malate DRUG

10 mg, orally, once daily.

Also known as: Famitinib

Combined treatment group

Gemcitabine & oxaliplatin DRUG

hepatic arterial infusion, Day 1 of each 3-week cycle.

Also known as: GEMOX

Combined treatment group

Capecitabine DRUG

1250 mg/m², orally twice daily, Days 1-14 of each 3-week cycle, as postoperative adjuvant therapy.

Combined treatment group

S-1 DRUG

40 mg/m², orally twice daily, Days 1-28 of each 6-week cycle, as postoperative adjuvant therapy.

Combined treatment group

hepatic arterial infusion chemotherapy (HAIC) PROCEDURE

Hepatic arterial infusion chemotherapy with gemcitabine and oxaliplatin administered on Day 1 of each 3-week cycle.

Combined 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:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension

Interventions

SHR-1701; famitinib; gemcitabine-oxaliplatin regimen; Capecitabine; S 1 (combination)

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Feng Cheng, MD

  The First Affiliated Hospital with Nanjing Medical University

  STUDY DIRECTOR

Central Study Contacts

Professor Chen, MD

CONTACT

+86 13305170695; docchengfeng@njmu.edu.cn

Jianhua Rao Professor Rao, Ph.D.

CONTACT

+86 18262637266; raojh@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2026
• First Posted: September 29, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: September 29, 2026

Record last verified: 2026-09

Locations

CN (1)