HER2-positive Status, Metastatic PDAC
Conditions
Brief summary
Pancreatic cancer is an extremely high-mortality malignancy. The chemotherapy regimen of gemcitabine combined with nab-paclitaxel (GEM-NABP) serves as one of the first-line standard therapies for metastatic pancreatic cancer. Given that traditional dual HER2 blockade (pertuzumab + trastuzumab) has demonstrated preliminary efficacy in HER2-expressing solid tumors, the novel clinical strategy of dual HER2 blockade (HLX22 + trastuzumab) combined with GEM-NAP offers the potential to improve outcomes for patients with HER2-positive pancreatic cancer.
Interventions
DRUGHLX22 (Recombinant Humanized Anti-HER2 Monoclonal Antibody Injection) in Combination with Trastuzumab and Chemotherapy
Drugs: HLX22 (15 mg/kg IV) + trastuzumab (8 mg/kg loading dose → 6 mg/kg maintenance) + nab-paclitaxel (125 mg/m² IV) + gemcitabine (1000 mg/m² IV). Administration: Administered every 3 weeks until disease progression, unacceptable toxicity, or withdrawal.
Sponsors
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Shanghai Zhongshan Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Voluntary Participation Willingly participate in the clinical study; fully comprehend the study details and sign the Informed Consent Form (ICF); commit to and demonstrate capacity to complete all trial procedures. * Age and Gender Any gender; age ≥18 and ≤75 years at the time of ICF signing. * Diagnosis Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma (PDAC). * Prior Therapy \*No prior systemic antitumor therapy for metastatic PDAC. \*Exception: Patients who received one cycle of chemotherapy (nab-paclitaxel + gemcitabine) as initial treatment for newly diagnosed PDAC may enroll. \*Prior neoadjuvant/adjuvant therapy is permitted if completed \>6 months before enrollment, and treatment-related adverse events (AEs) have recovered to NCI-CTCAE ≤ Grade 1 (alopecia excluded). * Measurable Disease At least one measurable lesion per RECIST v1.1, assessed by the investigator. Target lesions must not be exclusively bone metastases. * HER2 Status \*HER2-positive defined by ASCO/CAP gastric cancer HER2 testing guidelines: IHC 3+ (primary or metastatic lesion), or IHC 2+ with ISH/FISH-positive confirmation. \*Note: ≤15 patients with IHC 2+/FISH-positive status may enroll. * Performance Status ECOG performance status 0 or 1 within 7 days prior to first dose. * Life Expectancy Expected survival ≥3 months. * Hepatitis B \*HBsAg-negative and HBcAb-negative. \*If HBsAg-positive or HBcAb-positive, HBV-DNA must be \<2500 copies/mL or 500 IU/mL (or within institutional normal range). * Hepatitis C \*HCV antibody-negative. * If HCV antibody-positive, HCV-RNA must be negative. * Exclusion: Co-infection of HBV and HCV (HBsAg/HBcAb-positive and HCV antibody-positive). * HIV Status HIV antibody-negative. * Organ Function Adequate organ function within 14 days before first dose (without transfusion, albumin, thrombopoietin, or CSF support): \*Hematology: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L Platelets ≥100 × 10⁹/L Hemoglobin ≥90 g/L \*Liver: Total bilirubin ≤1.5 × ULN AST/ALT ≤2.5 × ULN (≤5 × ULN if liver metastases present) Alkaline phosphatase ≤5.0 × ULN Albumin ≥25 g/L \*Renal: Creatinine clearance ≥50 mL/min (Cockcroft-Gault formula) \*Coagulation: INR ≤1.5 × ULN APTT ≤1.5 × ULN PT ≤1.5 × ULN * Contraception * Females of childbearing potential: Negative serum pregnancy test within 7 days before first dose. * All participants: Use of ≥1 medically approved contraceptive method (e.g., IUD, oral contraceptives, barrier devices) during treatment and for ≥7 months after last dose.
Exclusion criteria
* Other Malignancies History of other malignancies within 2 years prior to first dose, except: Curatively treated localized tumors (e.g., basal cell carcinoma, squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situ of prostate/cervix/breast/thyroid). * Prior Anthracycline Exposure Cumulative doxorubicin dose \> 360 mg/m² (or equivalent): Equivalent agents: Epirubicin \>720 mg/m², mitoxantrone \>120 mg/m², idarubicin \>90 mg/m², or liposomal doxorubicin \>360 mg/m² doxorubicin-equivalent. If multiple anthracyclines were used, the total cumulative dose must not exceed 360 mg/m² doxorubicin-equivalent. * Prior HER2-Targeted Therapy Any previous HER2-targeted treatment (e.g., trastuzumab, pertuzumab). * Active Gastrointestinal Bleeding ≥ Grade 2 toxicity per NCI-CTCAE v5.0. * CNS Involvement Central nervous system (CNS) metastases and/or leptomeningeal metastases. * Cardiovascular Events History within 6 months prior to first dose: Cerebrovascular accident, myocardial infarction, unstable angina, or poorly controlled arrhythmias. QTc interval ≥450 ms (males) or ≥470 ms (females) (Fridericia formula). * Cardiac Dysfunction NYHA Class III-IV heart failure or left ventricular ejection fraction (LVEF) \< 55% by echocardiography. * Pulmonary/Infectious Conditions Interstitial lung disease (current or history). Active infection requiring systemic therapy or active tuberculosis. * Recent Live Vaccines Administration of live attenuated vaccines within 28 days prior to first dose (exception: inactivated influenza or COVID-19 vaccines). * Major Surgery Within 28 days prior to first dose. * Radiotherapy Curative radiotherapy within 28 days prior to first dose. * Concurrent Clinical Trials Current participation in other interventional studies or use of investigational drugs/devices within 28 days prior to first dose. * Hypersensitivity Known severe allergy to monoclonal antibodies or excipients of the study drugs. * Substance Abuse History of illicit drug use or psychiatric medication abuse. * Pregnancy/Lactation Pregnant or breastfeeding women. * Other Exclusionary Factors Any condition deemed by the investigator to: Compromise patient safety or data integrity. Require concomitant treatment for severe comorbidities (including psychiatric disorders). Exhibit critically abnormal laboratory values. Pose significant social/familial impediments to study completion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) assessed by investigators per RECIST v1.1. | up to 36 months |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS) | up to 12 months |
| Overall Survival (OS) | up to 36 months |
| Disease Control Rate (DCR) | up to 36months |
| Duration of Response (DOR) | up to 36 months |
| Incidence of Adverse Events (AEs) | up to 36 months |
Countries
China
Outcome results
None listed