Second-Line Therapy for Unresectable or Metastatic Biliary Tract CancerPhase 2NCT07530445
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
A Phase 2 study testing Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QD in people with Second-Line Therapy for Unresectable or Metastatic Biliary Tract Cancer, run by Sun Yat-sen University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Second-Line Therapy for Unresectable or Metastatic Biliary Tract Cancer
- What is being tested?
- Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QD
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 23 Mar 2026to 30 Dec 2027
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects voluntarily agree to participate in the study, sign the informed-consent form, demonstrate good compliance, and are willing to attend follow-up visits.
- Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary-tract cancer (gallbladder carcinoma, cholangiocarcinoma, or ampullary carcinoma of pancreaticobiliary type).
- Age 18-70 years (inclusive) at the time of informed consent, either male or female.
- ECOG performance status 0-1 and life expectancy ≥ 12 weeks.
- Received one prior line of systemic therapy containing a platinum agent, gemcitabine, or fluoropyrimidine (non-taxane), with or without PD-1/PD-L1 antibody.
- Patients who develop distant metastasis after curative-intent surgery are eligible if they received adjuvant chemotherapy without a taxane and relapse < 6 months after completion of adjuvant therapy.
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- At least one measurable lesion according to RECIST v1.1:
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- .Lesion diameter ≥ 10 mm on contrast-enhanced MRI or CT.
- .Lesions treated with prior local therapy may be considered measurable if they have progressed and meet RECIST v1.1 criteria.
- .Lesions previously treated with radioactive seed implantation cannot be used as target lesions.
- 8.No clinically significant cardiovascular, pulmonary, cerebral, or other major organ dysfunction.
- 9.Adequate Major Organ and Bone-Marrow Function Criteria
- Hematology • White blood cell (WBC) count ≥ 4.0 × 10⁹/L
- Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L
- Platelet count ≥ 75 × 10⁹/L
- Hemoglobin ≥ 80 g/L
- Coagulation
- International Normalized Ratio (INR) ≤ 1.5 × upper limit of normal (ULN)
- Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN
- Liver Function
- Total serum bilirubin ≤ 1.5 × ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN - Patients with concurrent liver metastases may be enrolled if ALT/AST ≤ 5 × ULN
- For obstructive jaundice: serum total bilirubin must be ≤ 1.5 × ULN after adequate internal or external biliary drainage
- Serum albumin ≥ 30 g/L
- Renal Function
- Serum creatinine ≤ 2 × ULN
- Calculated creatinine clearance (CCr) ≥ 40 mL/min (Cockcroft-Gault or equivalent)
- Urinalysis
- Urine protein < 2+ on dipstick
- If urine protein ≥ 2+, a 24-hour urine collection is required and must show total protein < 1.0 g to permit enrollment
- Thyroid Function
- Thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) all within ±10 % of the institutional normal range
- Patients with non-autoimmune hypothyroidism whose FT3/FT4 levels are maintained within the normal range on stable replacement therapy are eligible
- If TSH falls outside the above range, FT3, FT4, and clinical status must be assessed; subjects may be enrolled if findings indicate a non-acute, stable condition
- Cardiac Function
- Left ventricular ejection fraction (LVEF) ≥ 60 % as determined by two-dimensional echocardiography.
- 10.Contraception requirements
- Women of child-bearing potential must use a medically acceptable contraceptive method (e.g., IUD, oral contraceptive, condom) from screening through 6 months after the last dose of study drug; must have a negative serum or urine β-hCG test within 7 days before enrollment and must not be breastfeeding.
- Men with partners of child-bearing potential must use effective contraception during the study and for 6 months after the last dose.
Who cannot join
- Known hypersensitivity to any component of the study drugs (QL1706, albumin-bound paclitaxel, or lenvatinib).
- Prior anti-cancer therapy within specified wash-out periods before the first dose of study treatment:
- Fluoropyrimidines (e.g., S-1, capecitabine): ≤ 2 weeks
- Other cytotoxic chemotherapy: ≤ 3 weeks
- Small-molecule targeted therapy: ≤ 2 weeks
- Biologic therapy, large-molecule targeted therapy, or immunotherapy: ≤ 4 weeks
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- Histologic diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or undifferentiated carcinoma of the biliary tract.
- Obstructive jaundice that has not been adequately relieved (bilirubin not reduced to protocol-specified limits).
- Other malignancies within the past 5 years, except adequately treated basal-cell or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix.
- Any history or current evidence of brain metastases.
- Hepatic tumor burden ≥ 70 % of total liver volume, as determined by the investigator.
- Major surgery or invasive procedure within 4 weeks prior to enrollment, unless wound healing is complete (exceptions: venous catheterization, percutaneous drainage, or biliary drainage for obstructive jaundice).
- Loco-regional anti-tumor therapy within 4 weeks, including trans-arterial chemoembolization (TACE), cryoablation, or radiofrequency ablation of liver metastases.
- Clinically significant electrolyte disturbances, as judged by the investigator.
- Uncontrolled hypertension (systolic ≥ 140 mmHg and/or diastolic ≥ 90 mmHg) despite optimal medical management.
- High risk of fatal vascular invasion/bleeding in the opinion of the investigator (e.g., tumor likely to erode a major vessel during the study).
- Bleeding diathesis or significant bleeding history within 3 months, including:
- > 30 mL bleeding, hematemesis, melena, or hematochezia
- Hemoptysis (> 5 mL fresh blood within 4 weeks)
- Congenital or acquired coagulopathy
- Clinically relevant hemorrhagic events (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcer).
- Clinically significant cardiovascular disease, including:
- Acute myocardial infarction, severe/unstable angina, or coronary artery bypass graft surgery within 6 months
- New York Heart Association (NYHA) class > II congestive heart failure
- Symptomatic ventricular arrhythmias requiring medication
- QTc interval ≥ 480 ms on ECG.
- Active or uncontrolled severe infection ≥ CTCAE grade 2.
- Persistent toxicity > CTCAE grade 2 from prior anti-cancer therapy (except alopecia, lymphopenia, or ≤ grade 2 oxaliplatin-related neuropathy). Patients with prior immune-related adverse events that have resolved to baseline or are stable on replacement therapy may be enrolled after specialist consultation.
- Pregnancy (positive pregnancy test) or lactation.
- Any condition that, in the investigator's opinion, would compromise patient safety or data integrity, including:
- Seizure disorder requiring treatment
- Clinically significant metabolic, physical, or laboratory abnormalities
- Any disease state that could interfere with study participation or result in undue risk.
- Known HIV infection or clinically significant chronic liver disease, including:
- Active hepatitis B virus (HBV) infection (HBV DNA > 1 × 10⁴ copies/mL or > 2000 IU/mL)
- Hepatitis C virus (HCV) infection with detectable HCV RNA (> 1 × 10³ copies/mL)
- Other hepatitis, cirrhosis.
- Active or suspected autoimmune disease (e.g., myasthenia gravis, myositis, autoimmune hepatitis, SLE, RA, inflammatory bowel disease, MS, vasculitis, glomerulonephritis, uveitis, hypophysitis). Exceptions may apply for vitiligo, psoriasis, or thyroiditis that is controlled with replacement therapy.
- Any social or medical condition (e.g., alcohol or drug abuse, severe psychiatric illness) that, in the investigator's judgment, could interfere with adherence to study procedures, compromise safety, or lead to premature study discontinuation.
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
Zhiqiang Wang, guangzhou, Other (Non U.S.) 510000 Recruiting
Guangzhou
Zhiqiang Wang, +8613825122020, wangzhq@sysucc.org.cn
About this study
Official title: A Single-Center, Single-Arm, Open-Label 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
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.
- Being tested
- Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QD
- Medical subject headings
- Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QDDrug
Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QD
| Study group | Role | What they receive |
|---|---|---|
| iparomlimab and tuvonralimab (QL1706) in Combination with Albumin-Bound Paclitaxel and Lenvatinib | Experimental | Not described Receives: Drug: Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QD |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month progression-free survival (PFS) rate
the percentage of patients who are still alive and have not experienced radiologic disease progression or death at 6 months from the start of treatment.
Measured: 2 years
Secondary outcomes (6)
Objective response rate (ORR)
The ratio of patients who are evaluated as CR or PR
Measured: 2 years
Disease control rate (DCR)
Defined as the proportion of patients whose tumors shrink or remain stable for a certain period of time, including CR, PR and SD
Measured: 2 years
Duration of response (DOR)
defined as the time between the first assessment of a tumor as PR or CR and the first assessment as PD or any cause of death
Measured: 2 years
Median progression-free survival (mPFS)
The time from treatment initiation until half of the patients have either experienced objectively documented disease progression or died from any cause, whichever occurs first.It is estimated from Kaplan-Meier curves and serves as a key indicator of how long a therapy keeps the cancer under control in at least 50 % of treated individuals.
Measured: 2 years
Median Overall Survival (mOS)
The point in time (often expressed in months or years) after treatment initiation at which exactly 50 % of the patients in a study group are still alive. It is derived from a Kaplan-Meier survival curve and serves as a key summary measure of how long a therapy prolongs life in a given population .
Measured: 2 years
Time to disease progression (TTP)
Time from first dose to first documented disease progression
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2026
- Study start23 Mar 2026 (estimated)
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Second-Line Therapy for Unresectable or Metastatic Biliary Tract CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe 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
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhiqing Wang, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07530445
- Sponsor's protocol ID
- HPBTC-02
- Status last verified
- Mar 2026
- First submitted
- 18 Dec 2025
- Last updated
- 15 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Center, Single-Arm, Open-Label 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
- ClinicalTrials.gov ID
- NCT07530445
- Acronym / sponsor ID
- HPBTC-02
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 23 Mar 2026 (estimated)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 15 Apr 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| iparomlimab and tuvonralimab (QL1706) in Combination with Albumin-Bound Paclitaxel and Lenvatinib | Experimental | Drug: Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QD |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Subjects voluntarily agree to participate in the study, sign the informed-consent form, demonstrate good compliance, and are willing to attend follow-up visits.
- Histologically or cytologically confirmed unresectable locally advanced or metastatic biliary-tract cancer (gallbladder carcinoma, cholangiocarcinoma, or ampullary carcinoma of pancreaticobiliary type).
- Age 18-70 years (inclusive) at the time of informed consent, either male or female.
- ECOG performance status 0-1 and life expectancy ≥ 12 weeks.
- Received one prior line of systemic therapy containing a platinum agent, gemcitabine, or fluoropyrimidine (non-taxane), with or without PD-1/PD-L1 antibody.
Key exclusion criteria (39 listed)
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 |
|---|---|---|
| Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QDDrug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QD | Drug | iparomlimab and tuvonralimab (QL1706) in Combination with Albumin-Bound Paclitaxel and Lenvatinib |
Primary outcome
6-month progression-free survival (PFS) rate
Time frame: 2 years
the percentage of patients who are still alive and have not experienced radiologic disease progression or death at 6 months from the start of treatment.
6 secondary outcomes
Objective response rate (ORR)
Time frame: 2 years
Disease control rate (DCR)
Time frame: 2 years
Duration of response (DOR)
Time frame: 2 years
Median progression-free survival (mPFS)
Time frame: 2 years
Median Overall Survival (mOS)
Time frame: 2 years
Time to disease progression (TTP)
Time frame: 2 years
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 15 Apr 2026.
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 Drug: QL1706 5mg/kg, iv drip,d1,Q3W; Albumin-Bound Paclitaxel 125mg/m2, iv drip, d1、d8, Q3W; Lenvatinib 8mg, po, QD in people with Second-Line Therapy for Unresectable or Metastatic Biliary Tract Cancer, run by Sun Yat-sen University 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 40 inclusion and 39 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: looking for participants now, as of the sponsor's last update on 15 Apr 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 Zhiqiang Wang (+8613825122020, wangzhq@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-month progression-free survival (PFS) rate (time frame: 2 years). 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 15 Apr 2026.