Pancreatic Cancer, RAS Mutations or Amplifications
Conditions
Brief summary
This study aims to evaluate the safety, tolerability, and efficacy of HRS-2329 in combination with other anti-tumor therapies in participants with advanced pancreatic cancer harboring RAS mutations or amplifications.
Interventions
DRUGHRS-2329 Tablet
HRS-2329 is a novel, potent, oral pan-RAS inhibitor. HRS-2329 is given orally (to be swallowed whole, not chewed). It should be taken orally within 30 minutes after breakfast each morning.
DRUGNimotuzumab
Nimotuzumab is a marketed drug, a recombinant humanized monoclonal antibody targeting the epidermal growth factor receptor (EGFR). Nimotuzumab is administered at 400 mg by intravenous infusion over at least 60 minutes on Days 1 and 8 of each 3-week cycle.
DRUGHS-20093
HS-20093 is a B7-H3 antibody-drug conjugate (ADC).
DRUGAdebrelimab
Adebrelimab is a recombinant humanized anti-PD-L1 monoclonal antibody injection. It specifically blocks the binding of PD-1 to PD-L1, thereby terminating the immunosuppressive signals transmitted through PD-1 to T cells. This enables T cells to re-recognize tumor cells and exert cytotoxic effects, ultimately inhibiting tumor growth. Adebrelimab injection is administered at 1200 mg by intravenous infusion on Day 1 of each 3-week cycle.
Sponsors
Zhejiang University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * Histopathologically confirmed locally advanced or metastatic pancreatic adenocarcinoma (originating from pancreatic ductal epithelium) that is not amenable to curative therapy. * RAS mutation or amplification detected in tumor tissue or blood (by RAS testing). * Prior anti-tumor therapy: 1. For cohort HRS-2329-A: at least one line of standard systemic therapy in the advanced setting; 2. For cohorts HRS-2329-B and HRS-2329-C: at most one line of standard systemic therapy in the advanced setting. * At least one measurable lesion according to RECIST version 1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1. * Life expectancy ≥ 3 months. * Adequate function of vital organs. * Use of appropriate contraceptive methods during the study period, and so forth. * Voluntary participation in this study with signed informed consent, good compliance, and willingness to cooperate with follow-up assessments.
Exclusion criteria
* Prior treatment with drugs similar to the investigational product. * Known presence of central nervous system (CNS) metastases. * Acute or chronic pancreatitis requiring clinical intervention. * Gastrointestinal disorders that may affect drug administration/absorption, including but not limited to dysphagia, malabsorption syndrome, refractory nausea, vomiting, or diarrhea, Crohn's disease, and ulcerative colitis. * Gastrointestinal obstruction, or signs/symptoms of gastrointestinal obstruction; however, patients who have undergone surgical intervention with complete resolution of the obstruction may be considered for screening. * Concurrent biliary obstruction with risk of biliary tract infection (patients with treatable biliary obstruction may be enrolled if adequate biliary drainage is achieved and the risk of biliary infection is resolved after treatment). * Third-space fluid collections (e.g., massive pleural effusion, ascites) that cannot be stabilised (i.e., no intervention required after drainage removal) within 2 weeks prior to enrolment; patients with only a small amount of fluid detected by imaging and without clinical symptoms may be enrolled. * Severe infection within 4 weeks prior to enrolment, such as severe pneumonia, bacteraemia, or infectious complications requiring hospitalisation; unexplained fever \>38.5°C within 2 weeks prior to enrolment ; signs/symptoms of infection requiring intravenous antibiotic therapy within 2 weeks prior to enrolment. * Severe cardiovascular or cerebrovascular diseases. * Known or suspected interstitial lung disease (isolated imaging findings of interstitial changes are not excluded). * History of definite neurological or psychiatric disorders, including epilepsy and dementia. * Non-healing wounds (severe, non-healing, or dehiscent), or unhealed fractures. * Adverse events from prior therapy not recovered to NCI-CTCAE Grade ≤1 at enrolment . * History of malignancies other than the primary tumour within 5 years prior to enrolment, with the exception of malignancies with low risk of metastasis and death, such as adequately treated carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin. * Active hepatitis B infection. * For Cohort C, conditions that are unsuitable for immunotherapy. * Known allergy to any component of any of the study drugs to be administered. * Any other condition that, in the investigator's judgement, may affect the study results or result in premature termination of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From enrollment to upto 2 years | The proportion of patients whose tumor size shrinks as complete response or partial response, as assessed by RECIST1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | From enrollment to upto 2 years | defined as the proportion of patients with advanced or metastatic cancer who have achieved a complete response (CR), partial response (PR), or stable disease (SD) as the best overall response, relative to the total number of evaluable patients. |
| Duration of Response | From enrollment to upto 2 years | defined as the time from the first documented objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the first documented disease progression (per RECIST 1.1 criteria) or death due to any cause, whichever occurs first. |
| Progression-Free Survival | From enrollment to upto 2 years | defined as the time from initiation of treatment until the first documented disease progression per RECIST 1.1 criteria, or death due to any cause, whichever occurs first. |
| Overall Survival | From enrollment to upto 2 years | defined as the time from initiation of treatment until death from any cause. |
| Adverse event | From enrollment to upto 2 years | Safety evaluation was done continuously during treatment by using CTCAE 5.0 |
Countries
China
Contacts
CONTACTTingbo Liang, MD.
CONTACTYiwen Chen, MD.
Outcome results
None listed