Study of KRAS-Specific Vaccine in Patients With KRAS-Mutated Solid Tumors

A Clinical Study of Safety, Immunogenicity and Preliminary Efficacy of mKRAS Antigen-Loaded eDCs (CAT-101) Monotherapy or Plus Tislelizumab (Anti-PD-1 mAb) in KRAS-G12C/D/R/V-Mutated Advanced Pancreatic Cancer and Other Solid Tumors

The purpose of this study is to evaluate the safety, immunogenicity and preliminary efficacy of engineered dendritic cells（eDCs）loaded with mKRAS antigen (CAT-101) alone or in combination with Tislelizumab (anti-PD-1 monoclonal antibody) among participants with KRAS-G12C/D/R/V mutated advanced pancreatic cancer and other solid tumors.

The primary objective of this study is to systematically evaluate the safety profile, immunogenicity, and preliminary clinical efficacy of mKRAS antigen-loaded engineered dendritic cells (eDCs, designated as CAT-101), administered either as monotherapy or in combination with Tislelizumab (an anti-PD-1 monoclonal antibody), in patients with KRAS-G12C/D/R/V-mutated advanced pancreatic cancer and other refractory solid tumors. Secondary objectives include exploring the correlation between treatment-induced immune responses and clinical outcomes, as well as characterizing the optimal administration regimen for this combination therapy.

Inclusion Criteria:（1）Age 18-75 years，Male or female ； （2）Participants with ECOG score of 0-1 and the life expectancy ≥6 months； （3）Sufficient organ function as defined by the following criteria: creatinine clearance of ≥45 mL/min;Serum AST and serum ALT, ≤3.0 x ULN (≤5 x ULN for patients with liver metastases); Total bilirubin (TBIL) and alkaline phosphatase (AKP or ALP) ≤2.0 × ULN (except for congenital hyperbilirubinemia, such as Gilbert syndrome, the direct bilirubin may be ≤1.5 × ULN); for patients with liver and/or bone metastases, alkaline phosphatase ≤5.0 × ULN; Left ventricular ejection fraction ≥45% (by echocardiography or MUGA) (4) pregnancy test for women must be negative, and or must not be breastfeeding; participants with childbearing potential must agree to use effective contraception from the signing of the informed consent form until 1 year after the use of the study drug; (5) Willing to sign the informed consent form (ICF); （6）HLA-A*1101+ Participants with histologically confirmed advanced solid tumors (such as pancreatic ductal adenocarcinoma, non-small cell lung cancer, etc.) and harboring at least one of the targeted KRAS mutants （G12C/D/R/V）; (7)Participants who have failed standard treatment or who have no standard treatment options or who have minimal residual disease (MRD) after standard treatment , as well as those have unresectable locally advanced or metastatic solid tumors but currently unsuitable for standard treatment.

(8) Participants must have measurable lesions detected by computed tomography (CT) or magnetic resonance imaging (MRI) (according to iRECIST criteria);

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Exclusion Criteria:(1) Patients received other investigational therapy or any chemotherapy, hormonal therapy, targeted therapy, epigenetic therapy, or treatment with invasive investigational medical devices within 4 weeks or 5 half-lives prior to the first vaccination (whichever is shorter):

(2)Patients received proteasome inhibitors and immunomodulators, radiotherapy, or approved Chinese traditional medicine within 2 weeks or 5 half-lives prior to the first vaccination(whichever is shorter), (3) patients with meningeal, brainstem, or spinal cord metastases and/or compression, or active central nervous system (CNS) metastases; Participants with asymptomatic brain metastases within 4 weeks before the first vaccination and who do not require steroid treatment for at least 14 days are eligible for enrolment.

(4) patients with active second primary malignancy; however, patients received curative treatment and without known active disease for ≥2 years or non-melanoma skin cancer patients who received adequately treatment and with no evidence of disease will be eligible for study entry (5) patients with severe uncontrolled infection (bacterial, viral, fungal, etc.) during the screening period; (6) known positive test results for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with peripheral blood hepatitis B virus (HBV) DNA titer above the normal range or positive for hepatitis C virus (HCV) antibody with peripheral blood HCV RNA titer above the normal range or positive for human immunodeficiency virus (HIV) antibody; positive syphilis test within 6 months prior to the vaccinations.

(7)Patients with symptomatic heart failure or other cardiac diseases such as severe arrhythmias:

• New York Heart Association (NYHA) Class III or IV congestive heart failure;
• Myocardial infarction or coronary artery bypass graft (CABG) or coronary stent implantation within ≤6 months prior to signing the ICF;
• Clinically significant ventricular arrhythmia, or history of unexplained syncope (excluding vasovagal or dehydration-related causes);
• History of severe non-ischemic cardiomyopathy; （8）patients with other diseases, including:
• Primary immunodeficiency;
• Stroke or seizure within 6 months prior to screening;
• Significant clinical evidence of dementia or altered mental status;
• Parkinson's disease or Parkinson-like movement disorders or history thereof;
• Uncontrolled hypothyroidism or hyperthyroidism; (9)Surgery within 2 weeks prior to the vaccination or planned surgery within 2 weeks after the vaccination, excluding local anesthesia; （10）Uncontrolled hypertension, hypercalcemia, or diabetes; （11）Vaccination with live attenuated vaccines within 1 month prior to the first infusion; （12） Patients who have undergone long-term systemic corticosteroid therapy; （13）Known severe allergic reactions to eDC products or their formulation components (e.g., albumin, IL-2) （14）eDC-KRAS preparation failed; （15）Researchers believe that other reasons are not suitable for clinical trials