Phase II Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Albumin-Bound Paclitaxel and Lenvatinib as Second-Line Therapy for Unresectable or Metastatic Biliary Tract Cancer

Summary

Biliary tract carcinoma (BTC) is a highly aggressive malignancy with rising incidence worldwide. Most patients present at an advanced stage and have a dismal prognosis. First-line gemcitabine-platinum plus PD-1/PD-L1 blockade has become the new standard, yet no established second-line therapy exists after progression on this regimen. Combining dual checkpoint inhibition (PD-1/CTLA-4) with anti-angiogenic therapy and chemotherapy may overcome primary resistance.Although several studies have evaluated immune-checkpoint inhibitors (ICIs) alone or combined with anti-angiogenic agents in advanced BTC, overall survival improvements remain modest, and enrolled patients have typically progressed after chemotherapy only. Thus, the optimal second-line regimen in the immunotherapy era-especially the efficacy and safety of combining ICIs with chemotherapy-warrants further investigation.Dual PD-1/PD-L1 plus CTLA-4 blockade can comprehensively reactivate anti-tumor immunity by relieving T-cell suppression and enhancing cytotoxic function. QL1706, developed by Qilu Pharmaceutical using the proprietary MabPair™ platform, is the first bispecific antibody simultaneously targeting PD-1 and CTLA-4, showing synergistic anti-tumor activity and favorable tolerability. Lenvatinib is a multi-target tyrosine-kinase inhibitor with anti-angiogenic and immunomodulatory properties.For patients progressing after first-line therapy, preliminary data indicate that combining ICIs with anti-angiogenic agents (VEGFR2 antibodies or TKIs) yields modest efficacy; however, prospective evidence-especially for those refractory to chemotherapy plus PD-1/PD-L1 inhibitors-is lacking. Therefore, we designed an exploratory clinical trial evaluating QL1706 combined with albumin-bound paclitaxel and lenvatinib as second-line treatment for unresectable or metastatic BTC, aiming to provide a safe and effective option, particularly for patients previously exposed to PD-1/PD-L1 inhibitors, to prolong survival and improve quality of life.

Timeline

Start

2026-03-23

Primary completion

2027-04-30

Completion

2027-12-30

Drugs

Indications

No indication recorded.