HRS-4642 Combined With Antitumor Agents for the Treatment of Perioperative Pancreatic Cancer

Prior treatment

• Prior systemic therapy for pancreatic cancer, including neoadjuvant chemotherapy or radiotherapy.
• Has not recovered from the toxicity and/or complications of prior interventions to NCI-CTCAE Grade ≤ 1 or the level specified in the inclusion/exclusion criteria.
• Received systemic immunosuppressive therapy within 14 days prior to randomization.
• Known or suspected interstitial lung disease; or presence within 6 months prior to randomization of moderate-to-severe pulmonary diseases that may interfere with the detection or management of drug-related pulmonary toxicity or significantly impair respiratory function.
• Gastrointestinal obstruction within 6 months prior to initiation of study treatment, or current signs and symptoms of gastrointestinal obstruction.
• Clinically significant bleeding episodes or a clear bleeding tendency within 6 months prior to randomization.
• Uncontrolled or severe cardiovascular/cerebrovascular disease, or arterial/venous thromboembolic events within 6 months prior to randomization; or arrhythmia, deep vein thrombosis, etc. requiring clinical intervention.
• Diagnosis of any other malignancy within 5 years prior to randomization.
• Serious infection within 28 days prior to the first dose; or active infection requiring therapeutic intravenous antibiotics within 2 weeks prior to initiation of study treatment.
• Active pulmonary tuberculosis infection within 1 year prior to enrollment.
• Active autoimmune disease requiring systemic treatment within 2 years prior to randomization.
• Administration of a live attenuated vaccine within 28 days prior to randomization, or anticipated need for live attenuated vaccination during study treatment.
• Participation in any other clinical drug trial within 4 weeks or 5 half-lives (whichever is longer) of the last study drug administration prior to randomization.
• Major surgery (other than diagnostic procedure or biopsy) within 28 days prior to randomization; invasive minor surgery within 7 days prior to the first dose; or presence of a non-healing wound.

Other illness

• Currently has active autoimmune disease or a history of autoimmune disease with potential recurrence.
• Active hepatitis B or active hepatitis C.
• History of immunodeficiency or organ transplantation.
• Known hypersensitivity to any component of HRS-4642; or known severe hypersensitivity to any of the combination antitumor agents (including SHR-1316, gemcitabine, and nab-paclitaxel).
• Uncontrolled psychiatric illness, or known alcoholism, drug abuse, substance dependence, criminal detention, or other conditions that may interfere with completion of study procedures.

Other

• Distant metastatic lesions confirmed by imaging.
• Symptomatic moderate or severe ascites; uncontrolled or moderate-to-large pleural effusion or pericardial effusion.
• Carotid ultrasound demonstrating ≥ 50% stenosis, or carotid plaques with ≥ 2 high-risk features.
• Clinically significant acute or chronic pancreatitis.

• Able to provide informed consent, with a signed and dated IRB/EC-approved informed consent form (ICF), and willing and able to comply with the scheduled visits, treatment plan, examinations, and other protocol-required procedures.
• Aged between 18 and 75 years (inclusive) at the time of ICF signing; of either gender.
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
• Expected survival of at least 6 months.
• Histologically or cytologically confirmed pancreatic cancer originating from the pancreatic ductal epithelium.
• High-risk resectable pancreatic cancer (HR-RPC) or borderline resectable pancreatic cancer (BRPC).
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
• Adequate major organ function meeting the protocol-specified criteria.-