HAIC Plus QL1706 & Bevacizumab in Unresectable HER2-Negative ICC

ConditionIntrahepatic Cholangiocarcinoma

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age18-75

SponsorLianghe Lu

About this trial

Intrahepatic cholangiocarcinoma (ICC) has an increasing global incidence, and over 70% of patients are diagnosed at unresectable stages with limited survival benefits from standard first-line chemotherapy regimens. Hepatic arterial infusion chemotherapy (HAIC) delivers high-concentration local chemotherapy to liver tumors, while the PD-1/CTLA-4 dual antibody iparomlimab and tuvonralimab (QL1706) combined with bevacizumab can reshape the immunosuppressive tumor microenvironment and exert synergistic anti-tumor effects.The purpose of this study is to evaluate the efficacy and safety of HAIC-FOLFOX plus QL1706 and bevacizumab as first-line therapy for patients with unresectable HER2-negative intrahepatic cholangiocarcinoma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

1. Age ≥18 years and ≤75 years. 2. Good general condition with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1.

Disqualifiers

1. Severe impairment of major organs including heart, brain, lung or kidney; severe infection or other serious comorbidities (CTCAE v5.0 adverse events ≥ Grade 2) rendering the subject intolerant to study treatment.

Trial design

Design model

Single group

Treatments tested in this trial

hepatic arterial infusion chemotherapy (HAIC) combine with QL1706 and bevacizumab
Drug
Eligible patients were treated with HAIC plus QL1706 and bevacizumab. On the treatment day, continuous hepatic artery chemotherapy infusion was administered via an indwelling catheter connected to a micro-infusion pump. The infusion regimen included oxaliplatin 130 mg/m² over 3 hours, leucovorin 400 mg/m² over 1.5 hours, 5-FU 400 mg/m² over 2 hours, and 5-FU 2400 mg/m² over 46 hours. The catheter was removed after infusion completion. On the subsequent morning, patients received intravenous QL1706 (7.5 mg/kg) and bevacizumab (15 mg/kg), and were discharged after infusion. Treatment was repeated every 3-4 weeks for up to six cycles. Patients with favorable responses received continuous systemic maintenance therapy. Maintenance treatment was continued until death, intolerable toxicity, or loss of clinical benefit, with therapeutic regimens adjusted according to individual clinical status.

Treatment groups

35 Participants

are divided into 1 treatment group

Group A: Hepatic Arterial Infusion Chemotherapy (HAIC) Combine QL1706 and bevacizumabExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

objective response rate，ORR

ORR was defined as the proportion of patients achieving best overall response of complete response (CR) or partial response (PR) per RECIST 1.1.

Time frame

From first dose of study treatment until the earliest of progression, death, start of subsequent anti-tumor therapy, or data cutoff, assessed up to 24 months.

Secondary outcomes

disease control rate, DCR

DCR was defined as the proportion of patients achieving a best overall response of complete response (CR), partial response (PR), or stable disease.

Time frame

From first dose of study treatment until the earliest of progression, death, start of subsequent anti-tumor therapy, or data cutoff, assessed up to 24 months.

progression-free survival, PFS

PFS was defined as the time from randomization to first documented tumor progression per RECIST 1.1 or death from any cause, including death without prior disease progression. Patients without progression at data cutoff or lost to follow-up were censored at the date of last adequate tumor assessment.

Time frame

From date of randomization until the date of first documented progression or death, assessed up to 24 months.

Overall survival, OS

OS was defined as the time from first dose of study treatment to death from any cause. Patients who were alive at data cutoff or lost to follow-up were censored at the date last known to be alive.

Time frame

From date of first study treatment until death from any cause, assessed up to 36 months.

Safety evaluation

Treatment-related adverse events were assessed according to the CTCAE 5.0 criteria.

Time frame

From the date of first study treatment until 90 days after the last dose of study treatment.

Other outcomes

Exploratory Biomarker Analysis

Exploratory biomarker analyses will assess the correlation between baseline and on-treatment biological molecular characteristics and clinical efficacy outcomes including ORR, PFS and OS. Tumor tissues and serial peripheral blood samples collected during the study will be utilized for exploratory multi-omics sequencing and immunological detection, including single-cell sequencing and other high-throughput sequencing analyses. Dynamic changes of intratumor microenvironment, immune characteristics and molecular profiles before and after treatment will be explored and correlated with clinical prognosis. All biomarker analyses are descriptive without formal hypothesis testing, aiming to screen potential predictive and pharmacodynamic biomarkers, explore possible treatment resistance mechanisms, and provide scientific basis for individualized treatment optimization.

Time frame

From screening up to 24 months after the first dose of study treatment.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Lianghe Lu

Lead sponsor

Sun Yat-sen University

Sponsor institution

Source ClinicalTrials.gov

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