HRS-2329 for advanced solid tumors with RAS mutations or amplifications

A Phase I Study of HRS-2329 Evaluating Safety, Tolerability, and Pharmacokinetics in Subjects With Advanced Solid Tumors Harboring RAS Mutations or Amplifications

This trial will test the oral drug HRS-2329 in adults with advanced solid tumors that have RAS mutations or amplifications who have not responded to standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Jiangsu HengRui Medicine Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07189949 on ClinicalTrials.gov

What this trial studies

This is an open-label, multicenter Phase 1 study testing oral HRS-2329 in adults with advanced solid tumors that harbor RAS mutations or amplifications. The study's primary focus is safety, tolerability, and characterization of pharmacokinetics, with participants enrolled who have measurable disease and adequate organ function. Eligible patients are adults (18–75) with ECOG 0–1 and prior standard therapies exhausted; key exclusions include active CNS metastases, gastrointestinal disorders affecting drug absorption, unresolved prior treatment toxicities, or recent major surgery. Dose escalation and pharmacokinetic sampling will guide early safety and dose selection decisions before any expansion cohorts.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically or cytologically confirmed advanced solid tumors harboring RAS mutations or amplifications, ECOG 0–1, measurable disease by RECIST v1.1, life expectancy over three months, adequate organ function, and who have failed standard treatments are ideal candidates.

Not a fit: Patients with active central nervous system metastases, gastrointestinal conditions that impair oral drug absorption, unresolved Grade ≥2 toxicities from prior therapy, recent major surgery, or tumors without RAS mutation/amplification are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, HRS-2329 could offer a new targeted oral treatment option for patients with RAS-mutant or RAS-amplified advanced solid tumors.

How similar studies have performed: While some selective RAS-targeting agents (for example, KRAS G12C inhibitors) have shown benefit in specific tumor types, many RAS alterations remain difficult to target and this particular agent represents a relatively novel approach.

Eligibility criteria

Inclusion Criteria:

1. Have fully understood this study and are willing to sign the ICF, with good compliance and cooperation in follow-up;
2. Aged between 18-75 years old;
3. Participants with histologically/cytologically confirmed advanced solid tumors who have been previously tested or are confirmed by the central laboratory to harbor RAS mutations or amplifications and have failed standard treatment;
4. ECOG performance status (PS) score of 0 or 1;
5. Life expectancy \> 3 months;
6. At least one measurable lesion per RECIST v1.1;
7. Adequate organ function.

Exclusion Criteria:

1. Toxicity (e.g., gastrointestinal reaction and skin toxicity) from prior anti-tumor treatment has not recovered to Grade ≤ 1 or a level specified in the inclusion/exclusion criteria;
2. Presence of central nervous system (CNS) metastases;
3. Participants with gastrointestinal diseases that affect drug administration/absorption;
4. Participants who have undergone major surgery other than diagnosis or biopsy within 28 days before the first dose, or are expected to undergo major surgery during the study period;
5. Presence of serious pulmonary diseases;
6. Active tuberculosis or a history of active tuberculosis infection within 48 weeks prior to screening, regardless of whether they have been treated;
7. Active or persistent gastrointestinal bleeding within 6 months prior to screening;
8. History of allogeneic bone marrow or solid organ transplantation;
9. History of deep vein thrombosis or pulmonary embolism within 6 months prior to screening;
10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring clinical intervention;
11. Positive human immunodeficiency virus (HIV) (HIV1/2 antibodies), active chronic hepatitis B, or active hepatitis C (positive HCV antibody and positive HCV RNA);
12. Known history of hypersensitivity to any component of the drug product to be used in the study.

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Rongfu Mao

Conditions Advanced Solid Tumors Harboring RAS Mutations or Amplifications