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

Conditions

• Pancreatic Cancer
• RAS Mutations or Amplifications

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• HRS-2329 Tablet — DRUG
  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.
• 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.
• HS-20093 — DRUG
  HS-20093 is a B7-H3 antibody-drug conjugate (ADC).
• 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.

Study Details

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.

Key Dates

First listed

Jul 30, 2026

Start date

Aug 15, 2026

Status verified

Jul 2026

Primary completion

Aug 30, 2028

Completion

Dec 30, 2029

Study Design

Enrollment

80 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A
  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 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.
• Experimental: Arm B
  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 plus HS-20093, 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.
• Experimental: Arm C
  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 plus HS-20093 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.

Primary Outcome Measure

Objective Response Rate [ Time Frame: From enrollment to upto 2 years ]

Central Contacts

• Tingbo Liang, MD.
  +86 19941463683
  [email protected]
• Yiwen Chen, MD.
  [email protected]

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