Pancreatic Cancer
Conditions
Brief summary
The study is being conducted to evaluate the safety, tolerability and efficacy of HRS-4642 combined with adebelimab in subjects with locally advanced or metastatic pancreatic ductal adenocarcinoma.
Detailed description
This study is an open, single center, exploratory clinical trial aimed at evaluating the efficacy and safety of HRS-4642 combined with adebelimab in the treatment of patients with unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma. This study experiment is divided into two stages: dose exploration stage and efficacy exploration stage. During the dose exploration phase, RP2D was determined based on the safety, tolerability, and preliminary efficacy data of HRS-4642 combined with adelbizumab treatment, and then entered the efficacy exploration phase.
Interventions
DRUGHRS-4642
HRS-4642 will be administrated per dose level in which the patients are assigned.
DRUGAdebrelimab
Adebrelimab will be administrated per dose level in which the patients are assigned
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients volunteered to participate in this study and signed informed consent; 2. Age: ≥18 and ≤75 years old, male or female; 3. Advanced (metastatic or unresectable) Pancreatic ductal adenocarcinoma; and subjects must have at least one measurable lesion as defined by RECIST v1.1; 4. With failure or absence of standard treatment, and progress within 6 months of adjuvant therapy can also be included in the study; 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; 6. Life expectancy ≥ 12 weeks; 7. Adequate marrow and organ function; 8. AE caused by previous anti-tumor therapy must be restored to ≤ level 1 (CTCAE v5.0) or a stable state evaluated by the researcher, except for hair loss (any level) and peripheral neuropathy of level 2; 9. Female participants of childbearing age must undergo a pregnancy test within one week before the start of the study medication, and the result is negative. They are willing to use a medically recognized and efficient contraceptive method during the study period and within three months after the last administration of the study medication; For male participants whose partners are women of childbearing age, they should agree to use effective methods of contraception during the study period and within 3 months after the last study administration;
Exclusion criteria
1. Known to be allergic to the investigational drug or any of its components; 2. Have other active malignancies within 5 years; 3. Systemic antitumor therapy was received 4 weeks before the start of the study, and palliative radiotherapy was completed within 14 days before the first dose; 4. Previously received allogeneic hematopoietic stem cell transplantation or organ transplantation; 5. Accompanied by untreated or active central nervous system (CNS) metastases; 6. Within 6 months prior to entering the study, patients with severe cardiovascular and cerebrovascular thromboembolism; 7. Hypertension with poor drug control (continuous increase in systolic blood pressure ≥ 150mm Hg or diastolic blood pressure ≥ 100mmHg); 8. Late stage patients with symptoms that have spread to the internal organs and are at risk of life-threatening complications in the short term; 9. With interstitial lung disease, non-infectious pneumonia, severe and uncontrolled internal medicine diseases, acute infections, recent history of major surgery (within 28 days or not yet recovered from side effects); 10. Participated in clinical trials of any drug or medical device within 4 weeks prior to the first administration; 11. With congenital or acquired immune deficiency, such as people infected with HIV, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C antibody positive, and HCV-RNA higher than the detection limit of the analytical method) or combined with hepatitis B and hepatitis C infection; 12. With any active autoimmune diseases or a history of autoimmune diseases; 13. Received systemic treatment with corticosteroids or other immunosuppressants within 2 weeks prior to the first medication; 14. High risk of pancreatitis, serum amylase and/or lipase concentrations ≥ 3 times ULN; who have a simple increase in lipase, will be considered for inclusion by the researchers; 15. Other situations that researchers believe should not be included.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limited Toxicity (DLT) | Day 1 to Day 21 after the first combination therapy was administrated | A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness |
| Recommended phase II dose (RP2D) | Approximately 12 months | RP2D will be determined on the basis of evaluation on safety and efficacy data in dose escalation stages. |
| Objective Response Rate (ORR) | Up to approximately 12 months | Evaluated by RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to approximately 12 months | Time from the date of enrollment to data of death from any cause, or date of lost follow-up, whichever comes first, and otherwise censored at time last known alive. |
| Disease Control Rate (DCR) | Up to approximately 12 months | Evaluated by RECIST v1.1. |
| Adverse events (AEs) | From the first drug administration to within 90 days for the last adebrelimab dose | AEs are assessed by NCI-CTCAE v5.0 |
| Duration of Response (DOR) | Up to approximately 12 months | Evaluated by RECIST v1.1. |
| Progression Free Survival (PFS) | Up to approximately 12 months | Time from the date of enrollment to of disease progression, or death of any cause, or date of lost follow-up, whichever comes first, otherwise subject data were censored at time last known disease free. |
Countries
China
Contacts
Primary ContactSi Shi
Outcome results
None listed