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.
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:
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:
liangtingbo@zju.edu.cn+86 19941463683
This arm evaluates HRS-2329 in combination with nimotuzumab in participants with advanced pancreatic cancer harboring RAS mutations or amplifications who have received at least one prior line of therapy. Approximately 6 to 10 participants are planned to be enrolled initially to assess safety and preliminary efficacy, at the prespecified dose of HRS-2329 240 mg QD plus nimotuzumab 400 mg (D1,D8,Q3W). If the safety at this dose level is acceptable, enrollment may be expanded to 15-20 participants. During this period, the Safety Monitoring Committee (SMC) may review the cumulative safety and efficacy data and, after discussion, decide whether to adjust the dose, add other dose groups or dosing frequency arms for further exploration, or discontinue this combination regimen.
This arm evaluates HRS-2329 and HS-20093 with or without nimotuzumab in participants with advanced pancreatic cancer harboring RAS mutations or amplifications who are treatment-naïve or have received up to one prior line of standard systemic therapy. Approximately 30 participants are planned to be enrolled. The prespecified doses are HRS-2329 240 mg QD plus HS-20093 8.0 mg/kg Q3W, with or without nimotuzumab 400 mg on Day 1 and Day 8 of each 3-week cycle. The Safety Monitoring Committee (SMC) may review the cumulative safety and efficacy data and, after discussion, decide whether to adjust the dose, add other dose groups or dosing frequency arms for further exploration, or discontinue this combination regimen.
Alternative arm: This arm evaluates HRS-2329 and HS-20093 in combination with adebrelimab in participants with advanced pancreatic cancer harboring RAS mutations or amplifications who are treatment-naïve or have received up to one prior line of standard systemic therapy. Approximately 30 participants are planned to be enrolled. The prespecified doses are HRS-2329 240 mg QD plus HS-20093 8.0 mg/kg Q3W plus adebrelimab 1200 mg Q3W. The Safety Monitoring Committee (SMC) may review the cumulative safety and efficacy data and, after discussion, decide whether to adjust the dose, add other dose groups or dosing frequency arms for further exploration, or discontinue this combination regimen.
yiwenchen0705@126.com
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