A Pan-RAS Inhibitor in Combination With Anti-Tumor Therapy in Participants With Advanced Pancreatic Cancer

NCT07736612 | Not Yet Recruiting Phase 1

• 1 other identifier: CAPT08
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Pancreatic Cancer; RAS Mutations or Amplifications

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The proportion of patients whose tumor size shrinks as complete response or partial response, as assessed by RECIST1.1.

  From enrollment to upto 2 years

Secondary Outcomes (5)

• Disease Control Rate (DCR)

  From enrollment to upto 2 years

• Duration of Response

  From enrollment to upto 2 years

• Progression-Free Survival

  From enrollment to upto 2 years

• Overall Survival

  From enrollment to upto 2 years

• Adverse event

  From enrollment to upto 2 years

Study Arms (3)

Arm A

EXPERIMENTAL

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.

Drug: HRS-2329 Tablet; Drug: Nimotuzumab

Arm B

EXPERIMENTAL

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.

Drug: HRS-2329 Tablet; Drug: Nimotuzumab; Drug: HS-20093

Arm C

EXPERIMENTAL

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.

Drug: HRS-2329 Tablet; Drug: HS-20093; Drug: Adebrelimab

Interventions

HRS-2329 Tablet DRUG

HRS-2329 is a novel, potent, oral pan-RAS inhibitor that demonstrates strong inhibitory activity against a broad range of RAS-related targets, including KRAS G12V, KRAS G12C, KRAS G12D, KRAS wild-type, NRAS, and HRAS. HRS-2329 forms a ternary complex with Cyclophilin A (CypA) and the target, thereby blocking the binding of RAS-GTP to downstream proteins and disrupting downstream signaling pathways. This ultimately inhibits tumor cell proliferation and exerts anti-tumor effects. HRS-2329 240 mg is given orally (to be swallowed whole, not chewed) once daily on a 3-week cycle. It should be taken orally within 30 minutes after breakfast each morning.

Arm A; Arm B; Arm C

Nimotuzumab DRUG

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.

Arm A; Arm B

HS-20093 DRUG

HS-20093 is a B7-H3 antibody-drug conjugate (ADC) composed of the HS-20093 naked antibody (HS-20093 Ab) and a small-molecule toxin (HS-9265, also known as SHR169265) conjugated via a cleavable tetrapeptide linker. The anti-B7-H3 antibody is a humanized immunoglobulin G1 (IgG1) monoclonal antibody (mAb), and the small-molecule toxin, an exatecan derivative, is a topoisomerase I inhibitor. HS-20093 injection is administered at 8.0 mg/kg by intravenous infusion on Day 1 of each 3-week cycle.

Arm B; Arm C

Adebrelimab DRUG

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.

Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• For cohort HRS-2329-A: at least one line of standard systemic therapy in the advanced setting;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhejiang University: lead

Study Sites (1)

the First Affiliated Hospital, School of Medicine

Hangzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

nimotuzumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Central Study Contacts

Tingbo Liang, MD.

CONTACT

+86 19941463683; liangtingbo@zju.edu.cn

Yiwen Chen, MD.

CONTACT

yiwenchen0705@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: The chairman of the First Affiliated Hospital of Zhejiang University School of Medicine

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: July 30, 2026
• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): August 30, 2028
• Study Completion (Estimated): December 30, 2029
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)