Subjects with locally advanced or metastatic pancreatic cancer with KRAS G12D gene mutations
Conditions
Interventions
Control group:HRS-4642 United AG
Experimental group:HRS-4642 combined with AG and SHR-1316
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Have the ability to give informed consent, have signed and dated the IRB/EC-approved informed consent form, and are willing and able to comply with the examinations and other procedural requirements of planned visits for treatment; 2. The age at the time of signing the informed consent form is 18-75 years old (both ends are inclusive), and there is no gender limit; 3. ECOG score 0 or 1; 4. Expected survival >=12 weeks; 5. Subjects with confirmed KRAS G12D mutation unresectable locally advanced or metastatic pancreatic cancer and histologically confirmed pancreatic ductal adenocarcinoma; 6. Formalin-fixed, paraffin-embedded tumor tissue blocks or unstained tumor specimen sections should be provided, either archived or freshly obtained within 3 years before the first study treatment (freshly obtained is preferred). For subjects who are unable to provide tumor tissue samples that meet the above requirements, they need to discuss with the sponsor to determine whether to enroll (see the laboratory manual for tumor sample collection/collection and disposal methods); 7. At least one measurable lesion according to RECIST v1.1 criteria; 8. The function of important organs meets the following standards (no blood components or cell growth factors have been used for corrective treatment within 14 days before the first treatment), and the examination results must be completed within 7 days before the first study treatment: - White blood cell count (WBC) >= 3.0 × 10^9 /L (3,000/mm^3 ); - Neutrophil count (ANC) >=1.5×10^9 /L(1,500/mm^3 ); - Platelets >=100×10^9 /L(100,000/mm^3 ); - Hemoglobin >=9.0 g/dL (90 g/L); - Albumin >=3.0 g/dL; - Total bilirubin = 50 mL/min (calculated according to the standard Cockcroft-Gault formula); - Urine protein =2+, 24-hour urine protein quantification must be =50%; 9. Female subjects of childbearing potential must agree to use contraception and avoid donating eggs from the time of signing the informed consent form until 8 months after the last dose of the investigational drug. The serum pregnancy test must be negative within 7 days before administration and during the trial, and they must not be lactating. Male subjects whose partners are women of childbearing potential must agree to use contraception and avoid donating sperm from the time of signing the informed consent form until 8 months after the last dose of the investigational drug.
Exclusion criteria
Exclusion criteria: 1. Prior receipt of targeted therapy for KRAS G12D; 2. With untreated or active central nervous system (CNS) tumor metastasis. Subjects with a history of or current meningeal metastasis. Subjects can be enrolled if their CNS tumor metastasis has received adequate local treatment (surgery or radiotherapy) and does not require hormone therapy at least 2 weeks before the first dose, and their neurological recovery has returned to baseline (except for residual signs or symptoms related to CNS treatment); 3. Received any of the following treatments: 1) Plan to receive any other anti-tumor treatment during this trial; 2) Received other unmarketed clinical research drugs or treatments within 4 weeks before the first dose of the study; 3) Palliative radiotherapy or local treatment within 2 weeks before the first use of the study drug; anti-tumor traditional Chinese medicine within 2 weeks before the first use of the study drug; 4) Use of live attenuated vaccines within 4 weeks before the first use of the study drug, or the use of live attenuated vaccines is expected to be required during the study treatment. 4. Failure to recover from the toxicity and/or complications of previous interventions to NCI-CTCAE =3 interstitial pneumonitis previously treated with immune checkpoint inhibitors are not allowed to enroll in this study; 6. According to the common adverse event evaluation criteria NCI-CTCAE v5.0, subjects have grade >=3 serosal effusion or patients whose imaging shows the presence of large amounts of ascites (those who require therapeutic puncture and drainage within 2 weeks before starting study treatment, and those who only show a small amount of ascites on imaging and without clinical symptoms can be enrolled); 7. Gastrointestinal obstruction, gastrointestinal perforation and/or gastrointestinal fistula within 6 months before the start of study treatment; except for patients who have fully recovered after surgical treatment; 8. Have clinically significant bleeding symptoms (including hematemesis, melena, bloody stools, etc.) within 6 months before the start of study treatment. If hemorrhoidal bleeding is confirmed or only fecal occult blood is positive, you can be enrolled) or have a clear bleeding tendency; 9. Poorly controlled or serious cardiovascular and cerebrovascular diseases, arterial/venous thrombotic events within 6 months before entering t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival, PFS; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective relief rate;Incidence and severity of AE/SAE ;Disease control rate;Duration of relief;Overall Survival; | — |
Countries
China
Contacts
Public ContactYupei Zhao
Peking Union Medical College Hospital
Outcome results
None listed