Cryoablation combined with the dual-function PD-1/CTLA-4 antibody Apalulizumab for locally advanced pancreatic adenocarcinoma after first-line AG failure

A Single-Arm, Open-Label Clinical Study of Cryoablation Combined With the Dual-Function Antibody PD-1/CTLA-4 (Apalulizumab) for the Treatment of Locally Advanced Pancreatic Cancer Following Failure of First-Line AG Therapy

This Phase 2 study will test whether combining tumor cryoablation with the dual-function antibody Apalulizumab helps people with locally advanced pancreatic cancer whose disease progressed after first-line AG chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: chemotherapy, Apalulizumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07306286 on ClinicalTrials.gov

What this trial studies

This single-center Phase 2 interventional trial combines local tumor cryoablation with systemic therapy using a dual-function PD-1/CTLA-4 antibody (Apalulizumab) in patients with locally advanced pancreatic ductal adenocarcinoma who failed first-line AG therapy. Participants must have progressed on or been intolerant to prior AG chemotherapy and meet baseline organ function and ECOG 0–2 criteria before enrollment. The main goals are to collect safety data and preliminary signals of antitumor activity to inform second-line treatment options. Treatments and follow-up visits are conducted at Ruijin Hospital with imaging and laboratory monitoring to track responses and adverse events.

Who should consider this trial

Good fit: Adults (≥18 years) with pathologically confirmed locally advanced pancreatic ductal adenocarcinoma who progressed on or were intolerant to prior standard AG chemotherapy, have ECOG performance status 0–2, and meet specified laboratory and organ function requirements are eligible.

Not a fit: Patients with widely metastatic disease, ECOG performance status >2, or significant organ dysfunction that fails to meet the trial's laboratory limits are unlikely to benefit from this localized-plus-immunotherapy approach.

Why it matters

Potential benefit: If successful, the combination could improve local tumor control and stimulate systemic anti-tumor immunity, offering a new second-line option for patients with locally advanced pancreatic cancer after AG failure.

How similar studies have performed: Early-phase work combining local ablation with immune checkpoint inhibitors has shown promising signals in small cohorts, but robust evidence is limited and the use of a bifunctional PD-1/CTLA-4 antibody like Apalulizumab is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Aged 18 years and above, with no gender restrictions;
* Pathologically confirmed pancreatic cancer (originating from the pancreatic ductal epithelium), with clinical records indicating locally advanced pancreatic cancer;
* Clinical records indicating previous failure of standard AG treatment (having received at least one cycle of standardized chemotherapy, with disease progression or intolerance during treatment, or disease progression after the end of treatment);
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2;
* Adequate organ function, meeting the following criteria:

  a. Hematological tests:
  1. Neutrophils ≥ 1.5 × 10⁹ /L;
  2. White blood cells ≥ 3.0 × 10⁹ /L;
  3. Platelets ≥ 85 × 10⁹ /L;
  4. Hemoglobin ≥ 70 g/L; b. Biochemical tests:

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  1. Total bilirubin ≤ 2× upper limit of normal (ULN) (for subjects with biliary obstruction, after biliary drainage ≤ 2.5 × ULN);
  2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in metastatic subjects ≤ 5 × ULN;
  3. Albumin level ≥ 28 g/L;
  4. Creatinine clearance rate ≥ 60 ml/min; c. Cardiac function tests:

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  1. Normal electrocardiogram (ECG) or ECG abnormalities deemed clinically insignificant by the investigator;
  2. Left ventricular ejection fraction (LVEF) ≥ lower limit of normal;
* At least 3 weeks post-surgery, radiotherapy, chemotherapy, or other anti-tumor treatments, with general physical condition or related adverse reactions having recovered (toxicity ≤ grade 1) or stabilized;
* Willing to participate and sign the informed consent form;
* Good compliance and agreement to cooperate with survival follow-up.

Exclusion Criteria:

* Metastatic pancreatic cancer or has previously undergone interventional treatment for pancreatic cancer;
* Subjects with ascites requiring clinical intervention (including moderate to large amounts of ascites; subjects with ascites need to be stable for more than 4 weeks after drainage);
* Clinically severe gastrointestinal diseases (including bleeding, infectious inflammation, perforation, obstruction, or diarrhea greater than grade 1);
* NRS pain score ≥ 4 after standardized treatment with analgesics;
* Second primary malignancy within 5 years (except cured carcinoma in situ, basal cell, or squamous cell skin cancer; subjects with other previous tumors can be enrolled if there has been no recurrence within 5 years);
* Uncontrolled cardiovascular or cerebrovascular diseases with clinical symptoms, including but not limited to: ① NYHA class III or higher heart failure; ② unstable angina; ③ myocardial infarction or stroke within 6 months; ④ supraventricular or ventricular arrhythmias requiring treatment or intervention; ⑤ uncontrolled hypertension (systolic blood pressure \&gt; 150 mmHg and/or diastolic blood pressure \&gt; 90 mmHg despite optimal treatment);
* Known active hepatitis B subjects (HBsAg positive and HBV DNA ≥ 10³ copies or ≥ 1000 U/ml);
* Active infection or unexplained fever \&gt; 38.5°C during the screening period or on the day of administration (subjects with fever caused by tumors can be enrolled as judged by the investigator), which, in the investigator\&#39;s judgment, would affect the subject\&#39;s participation in this trial or interfere with the evaluation of efficacy;
* Known allergy to any components of irinotecan hydrochloride liposome, other liposomes, oxaliplatin, 5-FU, LV, or S-1;
* Pregnant or breastfeeding women;
* Women of childbearing potential with a positive blood (urine) pregnancy test during the screening period (both male and female subjects should use reliable contraception during the trial and for 3 months after the last dose to prevent pregnancy);
* Subjects with other medical or social issues that, in the investigator\&#39;s judgment, might affect their ability to sign informed consent, participation in the trial, or interpretation of the trial results;
* Patients with an estimated survival time of ≤ 3 months are not included in this study.

Where this trial is running

Shanghai, Shanghai Municipality

• Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Zhongmin Wang, Doctor

Conditions Pancreatic Adenocarcinoma Locally Advanced