Chiauranib Plus PD-1 Inhibitor, Albumin-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

NCT07445295 | Not Yet Recruiting Phase 3

• 1 other identifier: CAR304
• Study Type: interventional
• Target: 558
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase III, multi-center study to evaluate the efficacy and safety of chiauranib plus plus toripalimab, albumin-paclitaxel and gemcitabine as first-line therapy in patients with metastatic pancreatic ductal adenocarcinoma. The study includes two period: Run-in period and Randomized controlled period. The Run-in period is a single-arm, open-label study enrolling approximately 20 participants, who received the combination therapy of chiauranib plus toripalimab, albumin-paclitaxel and gemcitabine. The Randomized controlled period is a randomized, double-blind, parallel-controlled study enrolling approximately 538 participants, who are 1:1 randomly assigned to the experimental arm(chiauranib plus Toripalimab, albumin-paclitaxel and gemcitabine) or the control arm (Chiauranib placebo plus toripalimab placebo, albumin-paclitaxel and gemcitabine).

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events

  Defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAEV5.0)

  Run-in period.From the enrollment until 28 days after the last dose

• OS

  Overall survival

  Randomized controlled period. From the first dose to death or end of study, an average of 2 year

Secondary Outcomes (11)

• ORR

  Run-in period and Randomized controlled period. From the first dose to disease progression or end of study, an average of 2 year

• DoR

  Run-in period and Randomized controlled period. From the first dose to disease progression or end of study, an average of 2 year

• DCR

  Run-in period and Randomized controlled period. From the first dose to disease progression or end of study, an average of 2 year

• PFS

  Run-in period and Randomized controlled period. From the first dose to disease progression or end of study, an average of 2 year

• OS

  Run-in period. From the first dose to death or end of study, an average of 2 year

Study Arms (2)

Chiauranib plus toripalimab, albumin-paclitaxel and gemcitabine

EXPERIMENTAL

Drug: Chiauranib; Drug: Toripalimab Injection; Drug: Albumin-paclitaxel Injection; Drug: Gemcitabine Injection

Chiauranib placebo plus toripalimab placebo, albumin-paclitaxel and gemcitabine

PLACEBO COMPARATOR

Drug: Albumin-paclitaxel Injection; Drug: Gemcitabine Injection; Drug: Chiauranib placebo; Drug: Toripalimab Injection placebo

Interventions

Chiauranib DRUG

50 mg, oral administration once daily

Chiauranib plus toripalimab, albumin-paclitaxel and gemcitabine

Toripalimab Injection DRUG

3mg/kg, maximum dose 240mg, administered intravenously on Days 1 and 15 of each 28-day cycle

Chiauranib plus toripalimab, albumin-paclitaxel and gemcitabine

Albumin-paclitaxel Injection DRUG

125 mg/m\^2, administered intravenously on Days 1, 8 and 15 of each 28-day cycle

Chiauranib placebo plus toripalimab placebo, albumin-paclitaxel and gemcitabine; Chiauranib plus toripalimab, albumin-paclitaxel and gemcitabine

Gemcitabine Injection DRUG

1000 mg/m\^2, administered intravenously on Days 1, 8 and 15 of each 28-day cycle

Chiauranib placebo plus toripalimab placebo, albumin-paclitaxel and gemcitabine; Chiauranib plus toripalimab, albumin-paclitaxel and gemcitabine

Chiauranib placebo DRUG

50 mg, oral administration once daily

Chiauranib placebo plus toripalimab placebo, albumin-paclitaxel and gemcitabine

Toripalimab Injection placebo DRUG

3mg/kg, maximum dose 240mg, administered intravenously on Days 1 and 15 of each 28-day cycle

Chiauranib placebo plus toripalimab placebo, albumin-paclitaxel and gemcitabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and voluntarily sign the written informed consent form.
• Age 18-75 years on the day of signing the informed consent form, male or female.
• Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma.
• No prior systemic therapy for metastatic pancreatic ductal adenocarcinoma. Participants who have received prior induction chemotherapy, concurrent radiotherapy, or adjuvant/neoadjuvant chemotherapy with curative intent, the interval of recurrence or metastasis must be at least 6 months after the last treatment.
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Previously received local therapy lesion can be considered as measurable lesion unless imaging-confirmed progression.
• ECOG Performance Status 0 or 1.
• Life expectancy≥3 months.
• Major organ functions meet the following criteria(no blood transfusions, hematopoietic growth factors, albumin and other medications considered by the investigator to be corrective therapy within 14 days prior to examination, except for iron supplements): Hematology: hemoglobin≥90g/L, absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelets≥100×10\^9/L. Biochemistry: serum creatinine≤1.5×ULN, total bilirubin≤1.5×ULN, AST/ALT≤2.5×ULN (≤5×ULN for patients with hepatic metastasis). Coagulation profile: INR \< 1.5×ULN(for participants undergoing prophylactic anticoagulation therapy, investigators should determine whether the INR is within a safe and effective therapeutic range).

You may not qualify if:

• Histological or cytological confirmed other pathological types, such as acinar cell carcinoma, neuroendocrine carcinoma, pancreablastoma, etc.
• During screening, tumor invades major vessels (e.g., pulmonary artery, superior vena cava, or inferior vena cava) and significant risk of hemorrhage judged by the investigator; or known history of aneurysm.
• Presence of active or untreated brain metastases, meningeal metastases, spinal cord compression, or leptomeningeal disease during the screening period. However, enrolment is permitted for subjects who meet the following requirements and have measurable lesion outside the CNS: asymptomatic after treatment and stable on imaging for at least 28 days prior to the first dose (e.g., no new or enlarging brain metastases) and have been off systemic glucocorticosteroids and anticonvulsant medications for at least 14 days prior to the first dose.
• Presence of clinically symptomatic pleural effusion, pericardial effusion or ascites requiring frequent drainage (≥1 time/month) during the screening period.
• Previous received Aurora kinase inhibitors, or systemic treatment of VEGF/VEGFR inhibitors such as bevacizumab, sorafenib, sunitinib, amlotinib, apatinib, and endostar, or immunotherapy drugs of PD-1, PD-L1, CTLA-4 inhibitors, etc.
• Previous radiation therapy, chemotherapy, immunotherapy, targeted therapy within 28 days prior to the first dose. Chinese patent medicine witn anti-malignancy effect approved by National Medical Products Administration within 14 days prior to the first dose.
• Presence of peripheral neuropathy of CTCAE v5.0 criteria, Grade 2 or higher.
• Major surgery (craniotomy, thoracotomy, or laparotomy) or serious unhealed wounds, ulcers, or fractures within 28 days prior to the first dose. Needle biopsy or other minor surgery (except for intravenous infusion) within 7 days prior to the first dose.
• Significant arterial/venous thrombotic events within 6 months prior to first dose, such as deep vein thrombosis and pulmonary embolism. Superficial vein thrombosis without safety risk judged by the investigator is permitted.
• Cardiac dysfunction or clinically meaningful cardiovascular disease, including: (1)New York Heart Association (NYHA) grade III\~IV congestive cardiac failure, unstable angina pectoris, and/or myocardial infarction within the 6 months prior to the first dose of the investigational drug, clinically significant arrhythmia unable to be controlled with medical treatment or left ventricular ejection fraction (LVEF) \<50% at screening. (2)Primary cardiomyopathies (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy). (3)Clinically significant history of prolonged QTc interval, or QTcF interval \>470ms for females or \>450 ms for males during the screening period. (4)Coronary heart disease with symptoms requiring medication. (5)Documentation of hypertension treatment with≥3 antihypertensive medications simultaneously within 14 days before the first dose of medication or systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg during the screening period (resting state, measured approximately every 5 minutes, averaged after three consecutive measurements, rounded to the nearest integer). (6)History of hypertensive crisis or hypertensive encephalopathy. (7)Other cardiovascular disease judged by the investigator to be unsuitable for enrolment.
• Active bleeding within 2 months prior to the first dose, or taking anticoagulants, such as warfarin, phenprocoumon (prophylactic low-dose aspirin and low-molecular heparin are permitted) during the screening period, or at high risk of bleeding judged by the investigator during screening period (e.g., esophageal varix associated with bleeding risk, locally active ulcer lesions, positive fecal occult blood that can not exclude gastrointestinal bleeding, intermittent haemoptysis) .
• Presence of significant gastrointestinal abnormalities during the screening period that may interfere with drug intake, transit or absorption (e.g. inability to swallow, chronic diarrhoea, post-small bowel resection or total gastrectomy), according to the investigator's judgment.
• History of gastrointestinal perforation and/or fistula, peptic ulcer disease, intestinal obstruction (including incomplete intestinal obstruction that requires parenteral nutrition), or biliary obstruction within 6 months prior to the first dose.
• History of other malignant tumors within 3 years prior to the first dose, except for those treated with expected curative outcomes, such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, ductal carcinoma in situ of the breast, localized prostate cancer, and papillary thyroid microcarcinoma.
• For urine protein≥2+ by urinalysis during the screening period, a 24-hour urine protein quantification test should be performed. The subject cannot be enrolled if the quantified urine protein is≥1g/24h. If the quantified urine protein is \<1g/24h, the subject can still be enrolled.

Sponsors & Collaborators

• Chipscreen Biosciences, Ltd.: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Interventions

chiauranib; toripalimab; Gemcitabine

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Xuelian Zhou

CONTACT

028-64907337; zhouxuelian@chipscreen.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2026
• First Posted: March 3, 2026
• Study Start: March 31, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)