A Phase II Clinical Study of HLX22 in Combination With Trastuzumab and Chemotherapy

Fudan University

Status and phase

Active, not recruiting

Phase 2

Conditions

Metastatic PDAC

HER2-positive Status

Treatments

Drug: HLX22 (Recombinant Humanized Anti-HER2 Monoclonal Antibody Injection) in Combination with Trastuzumab and Chemotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT07176702

HLX22-IIT-PDAC201

Details and patient eligibility

About

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.

Enrollment

45 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.