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Biliary Tract Cancer (BTC)Phase 2NCT07129018

Trastuzumab Rezetecan Combined With Pertuzumab and Iparomlimab and Tuvonralimab for Biliary Tract Cancer

A Phase 2 study testing Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Overexpression BTC and Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Moderate/Low BTC in people with Biliary Tract Cancer (BTC) and First-line Therapy, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

Based on unmet clinical needs, relevant research backgrounds, and scientific evidence, it is planned to conduct a prospective, dual-cohort exploratory study. The aim of this study is to explore the efficacy and safety of ricartuzumab combined with pertuzumab and epalrestat-vorolizumab in the first-line treatment of… Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Overexpression BTC and Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Moderate/Low BTC
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
63 participants
Where
No sites listed yet
Study dates
Nov 2025to Dec 2028
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must voluntarily participate in the trial, provide fully informed consent with signed written documentation, and demonstrate good compliance.
  • Age between 18 and 75 years (inclusive), calculated as of the day of signing the informed consent form; both male and female patients are eligible.
  • Patients must have histologically or cytologically confirmed locally advanced or metastatic biliary tract cancer, including: Cholangiocarcinoma (intrahepatic or extrahepatic) and Gallbladder carcinoma
  • HER2 Expression Criteria: HER2 Overexpression: IHC 3+ OR IHC 2+ with FISH-positive (gene amplification); HER2 Moderate/Low Expression: Moderate: IHC 2+ with FISH-negative (no gene amplification) Low: IHC 1+ (any level of HER2 staining)
  • Patients must not have received prior systemic anti-tumor therapy for advanced disease. Prior neoadjuvant/adjuvant chemotherapy and/or radiotherapy is permitted, provided ≥6 months have elapsed between the last dose and disease recurrence.
  • Patients must have at least one measurable lesion meeting RECIST v1.1 criteria, and the lesion must be suitable for repeated accurate measurements.
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  • ECOG performance status of 0 or 1;
  • estimated life expectancy ≥12 weeks;
  • Adequate organ and bone marrow function meeting all criteria below (within 14 days prior to treatment initiation): 1. Hematological Tests *(No transfusion, G-CSF use, or corrective medication within 14 days before screening)* Hemoglobin (Hb) ≥90 g/L Absolute Neutrophil Count (ANC) ≥1.5 × 10<sup>9</sup>/L Platelets (PLT) ≥75 × 10<sup>9</sup>/L 2. Biochemical Tests (No albumin infusion within 14 days before screening) Total Bilirubin (TBIL) ≤2 × ULN Gilbert's syndrome: ≤3 × ULN ALT/AST ≤3.0 × ULN Liver metastasis: ≤5 × ULN Serum Creatinine (Cr) ≤1.5 × ULN OR Creatinine Clearance (CrCl) ≥50 mL/min (Cockcroft-Gault formula);
  • Patients with detectable HBV DNA levels (≥10 IU/mL or above the lower limit of quantification per local laboratory assays) who are HBV-infected (HBsAg-positive and/or anti-HBc-positive) must receive antiviral therapy prior to treatment initiation according to institutional practice to achieve sufficient viral suppression. Antiviral therapy must be maintained throughout the study and for 6 months after the last dose of study treatment. Patients with positive anti-HBc but undetectable HBV DNA (<10 IU/mL or below the lower limit of quantification per local laboratory assays) do not require antiviral prophylaxis unless HBV DNA exceeds 10 IU/mL or reaches detectable levels during treatment monitoring.
  • Childbearing potential females: Negative pregnancy test (urine/serum) within 7 days pre-dose (serum result definitive if urine inconclusive). Sexually active with non-sterilized males: Use acceptable contraception from screening until 120 days post-last dose.
  • Non-sterilized males sexually active with childbearing-potential partners: Use effective contraception from screening until 120 days post-last dose. Discontinuation post-120 days requires investigator discussion.
  • Subjects must comply with visits, treatment, lab tests, and study requirements.

Who cannot join

  • Histologically or cytologically confirmed ampullary carcinoma, small cell carcinoma, neuroendocrine tumors, sarcoma, mucinous cystic neoplasms, or other rare biliary tract malignancies.
  • Active other malignancies within 5 years or concurrently.
  • History of leptomeningeal disease, brain metastases, or current brain metastases.
  • Participation in other investigational drug trials within the past 3 months, or concurrent enrollment in another interventional clinical trial (observational/non-interventional studies or follow-up phases allowed).
  • Any condition deemed by the investigator to compromise safety or compliance, including: Uncontrolled systemic diseases (e.g., severe hypertension, moderate/severe symptomatic ascites) Uncontrolled/moderate-or-greater pleural/pericardial effusion Acute/chronic uncontrolled pancreatitis Active bleeding disorders, infections, or ILD/interstitial lung disease Severe chronic GI disorders with diarrhea Psychiatric illness/social circumstances affecting compliance History of allogeneic organ or bone marrow transplantation.
  • Within 12 months prior: NYHA Class ≥II congestive heart failure Unstable angina, myocardial infarction Poorly controlled arrhythmia or cerebrovascular accident LVEF <50% by echocardiogram QTc >480 ms (Fridericia method; average of 3 measurements if abnormal) Uncontrolled hypertension (SBP≥150 mmHg and/or DBP≥100 mmHg, average of ≥2 readings) History of hypertensive crisis or encephalopathy.
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  • Active autoimmune disease within 2 years or history of recurrent autoimmune disease (e.g., autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyper/hypothyroidism). (Except hypothyroidism controlled by hormone replacement)
  • Previous treatment with HER2-targeted agents, HER2-ADCs, or immunotherapy (e.g., checkpoint inhibitors/agonists, cell therapy). Therapeutic cancer vaccines excluded.
  • Prior anti-tumor therapy toxicities not recovered to CTCAE v5.0 Grade ≤1 (alopecia/lab abnormalities meeting inclusion criteria allowed per investigator).
  • Unexplained intra-abdominal gas unrelated to recent surgery/paracentesis.
  • Abdominal complications within 6 months: Abdominal fistula, gastrointestinal perforation, or abscess；Tumor invasion of adjacent organs (e.g., aorta, trachea) with high bleeding/fistula risk.
  • Immunodeficiency (e.g., HIV infection) or history of organ transplantation.
  • Active tuberculosis (TB): Active TB within 1 year prior to enrollment；Untreated active TB history >1 year prior.
  • Bleeding/thrombotic risks: Gastrointestinal bleeding within 6 months or high bleeding tendency；Known hereditary/acquired bleeding disorders or thrombophilia.
  • Surgical history: Major surgery within 4 weeks prior (excluding biopsies) or unhealed surgical wounds ；Planned major surgery during the study；Minor traumatic surgery within 7 days prior；
  • Severe/unhealed wounds, active ulcers, or untreated fractures.
  • CNS metastases (past or present).
  • Live attenuated vaccines: Administered within 28 days before the first study dose; Planned use during the study or within 60 days after the last dose.
  • Other exclusionary factors per investigator judgment (e.g., substance abuse, severe comorbidities, abnormal lab values, psychosocial circumstances).

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Chen Shi contact

027-85726192

shichen@hust.edu.cn

About this study

Official title: A Prospective, Open-Label, Multicenter Phase II Clinical Study of Trastuzumab Rezetecan Combined With Pertuzumab and Iparomlimab and Tuvonralimab as First-Line Therapy for HER2-Expressing Locally Advanced or Metastatic Biliary Tract Cancer

Based on unmet clinical needs, relevant research backgrounds, and scientific evidence, it is planned to conduct a prospective, dual-cohort exploratory study. The aim of this study is to explore the efficacy and safety of ricartuzumab combined with pertuzumab and epalrestat-vorolizumab in the first-line treatment of HER2-expressing locally advanced or metastatic biliary tract cancer. It is expected to provide more treatment options for biliary tract cancer patients, optimize treatment strategies, and improve patients' long-term survival rates.

Read the detailed description

The aim of this study is to explore the efficacy and safety of ricartuzumab combined with pertuzumab and epalrestat-vorolizumab in the first-line treatment of HER2-expressing locally advanced or metastatic biliary tract cancer. It is expected to provide more treatment options for biliary tract cancer patients, optimize treatment strategies, and improve patients' long-term survival rates.

Being tested
Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Overexpression BTC, Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Moderate/Low BTC
Keywords
Iparomlimab and Tuvonralimab, Pertuzumab, Trastuzumab-rezetecan, HER2-expressing, biliarytract cancer (BTC)
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.

  • Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Overexpression BTCDrug

    Also called Three-drug combination regimen

    Subjects received treatment with Iparomlimab and Tuvonralimab (5.0 mg/kg, iv, d1, q3w) and Trastuzumab-rezetecan (4.8 mg/kg, iv, d1, q3w) in combination with Pertuzumab (initial dose 840 mg, iv, followed by 420 mg, iv, d1, q3w). Study treatment continued until the occurrence of a protocol-specified treatment discontinuation event. Following the end of treatment, subjects will continue to undergo safety follow-up and survival follow-up. For subjects who discontinued treatment for reasons other than disease progression, periodic tumor imaging assessment follow-up will also continue after treatment cessation.

  • Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Moderate/Low BTCDrug

    Also called Three-drug combination regimen

    Subjects received treatment with Iparomlimab and Tuvonralimab (5.0 mg/kg, iv, d1, q3w) and Trastuzumab-rezetecan (4.8 mg/kg, iv, d1, q3w) in combination with Pertuzumab (initial dose 840 mg, iv, followed by 420 mg, iv, d1, q3w). Study treatment continued until the occurrence of a protocol-specified treatment discontinuation event. Following the end of treatment, subjects will continue to undergo safety follow-up and survival follow-up. For subjects who discontinued treatment for reasons other than disease progression, periodic tumor imaging assessment follow-up will also continue after treatment cessation.

Study groups in NCT07129018
Study groupRoleWhat they receive
HER2 Overexpression CohortExperimentalHER2 Overexpression ：IHC 3+ or IHC 2+/FISH +；
Receives: Drug: Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Overexpression BTC
HER2 Moderate/Low Expression CohortExperimentalHER2 Moderate/Low Expression：IHC 2+/FISH -（Moderate Expression）IHC 1+（Low Expression）；
Receives: Drug: Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Moderate/Low BTC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) by RECIST1.1

    Objective Response Rate (ORR) assessed by investigators based on the Response EvaluationCriteria in Solid Tumors version 1.1 (RECIST v1.1).

    Measured: Up to approximately 4 years

Secondary outcomes (7)

  1. Objective Response Rate (ORR) by mRECIST

    Objective Response Rate (ORR) assessed by investigators based on the modified Response Evaluation Criteria in Solid Tumors mRECIST.

    Measured: Up to approximately 4 years

  2. DCR

    The percentage of subjects who achieved complete response, partial response, or stable disease (SD) lasting for 6 weeks or longer, as determined by the investigator in accordance with RECIST v1.1 or mRECIST.

    Measured: Up to approximately 4 years

  3. OS

    The time from the date of the first drug administration to the death of the subject due to various reasons.

    Measured: Up to approximately 4 years

  4. TTP

    The time from the date of the first treatment to the occurrence of radiological disease progression, as determined by the investigator in accordance with RECIST v1.1 or mRECIST.

    Measured: Up to approximately 4 years

  5. DoR

    The time from the first documentation of objective response (CR or PR) to the first occurrence of radiological disease progression or death (whichever comes first), as determined by the investigator in accordance with RECIST v1.1 or mRECIST.

    Measured: Up to approximately 4 years

  6. PFS

    The time from the first treatment to the first occurrence of radiological disease progression or death (whichever comes first), as determined by the investigator in accordance with RECIST v1.1 or mRECIST.

    Measured: Up to approximately 4 years

  7. Incidence of Adverse Events (AEs)

    The percentage of patients in the safety analysis set who experienced specific adverse events during the study period.

    Measured: Up to approximately 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Aug 2025
  2. Study startNov 2025 (estimated)
  3. Primary completionNov 2027 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
63 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07129018
Sponsor's protocol ID
HER2-TRIP
Status last verified
Aug 2025
First submitted
11 Aug 2025
Last updated
19 Aug 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Overexpression BTC and Trastuzumab-rezetecan + Pertuzumab + Iparomlimab and Tuvonralimab for HER2 Moderate/Low BTC in people with Biliary Tract Cancer (BTC) and First-line Therapy, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology.

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 13 inclusion and 19 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: opening soon, as of the sponsor's last update on 19 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

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 Chen Shi (027-85726192, shichen@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) by RECIST1.1 (time frame: Up to approximately 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07129018.

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 19 Aug 2025.

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