Study of JYP0015 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

Official title

A Multi-center, Open-label, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of JYP0015 in Advanced Solid Tumors With RAS Mutation

Overview

Evaluate the safety and antitumor activity of JYP0015 in adults with specific RAS mutant advanced solid tumors.

Detailed description

This is a Phase 1/2, multicenter, open-label study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of JYP0015 in adult patients with advanced solid tumors harboring specific RAS mutations.

The study consists of two parts:

* Phase 1 (dose escalation) - Evaluates the safety, tolerability, and pharmacokinetic profile of JYP0015 monotherapy, preliminarily assesses efficacy, and determines the recommended dose (RD) for further evaluation. * Phase 2 (indication expansion) - Explores the therapeutic potential of JYP0015 monotherapy at the RD across four predefined cohorts:

1. Pancreatic ductal adenocarcinoma (PDAC) 2. Non-small cell lung cancer (NSCLC) 3. Colorectal cancer (CRC) 4. Other advanced solid tumors Phase 2 will assess both efficacy and safety within these cohorts.

JYP0015 is a potent, orally bioavailable pan-RAS inhibitor that selectively targets the active (ON) form of wild-type and mutant RAS across all three isoforms-HRAS, NRAS, and KRAS.

Interventions

• Drug JYP0015
  JYP0015 is an orally bioavailable pan-RAS inhibitor designed to target the active (ON) form of wild-type and mutant RAS across KRAS, NRAS, and HRAS isoforms. The drug will be administered orally, with dosing determined by the study protocol in the dose-escalation and indication-expansion phases.

Primary outcome measures

• Number of Participants with Dose-Limiting Toxicity (DLT) [Time frame: 21 days]
• Incidence and Severity of Treatment-Emergent Adverse Events (AEs) and Serious AEs [Time frame: Up to 3 years]
• Overall Response Rate (ORR) [Time frame: Up to 3 years]

Secondary outcome measures (4)

• Maximum Observed Blood Concentration (Cmax) of JYP0015 [Time frame: Up to 16 weeks]
• Time to Reach Maximum Blood Concentration (Tmax) of JYP0015 [Time frame: Up to 16 weeks]
• Duration of Response (DOR) [Time frame: Up to 3 years]
• Time to Response (TTR) [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

• Histologically or pathologically confirmed solid tumors with RAS mutation via molecular tests.
• Patients with RAS mutation who have disease progression or intolerance after adequate standard treatment
• Eastern Cooperative Oncology Group (ECOG) performance status in 0 or 1
• Adequate organ function

Exclusion criteria

• Presence of central nervous system (CNS) metastases; however, subjects with previously treated brain metastases may be enrolled if clinically stable.
• Gastrointestinal (GI) disorders that may interfere with drug administration/absorption, including but not limited to: Dysphagia or inability to swallow tablets， Malabsorption syndrome，Refractory nausea, vomiting, or diarrhea，Chronic GI diseases (e.g., Crohn's disease, ulcerative colitis)
• Congestive heart failure with New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) <50%.
• Any other condition deemed by the investigator to potentially compromise study outcomes or lead to premature termination, including but not limited to: Alcohol or substance abuse，Concurrent severe medical conditions (e.g., psychiatric disorders requiring active treatment)， Familial or social circumstances that may affect patient safety, compliance, or study data collection.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Questions to ask your doctor

• Is this trial appropriate for my diagnosis and stage?
• What is known about the study treatment and its risks?
• Would participation interfere with my current treatment?
• Which tests are needed to check the eligibility criteria?
• Are there similar trials closer to home?

What information a coordinator may need

• the exact diagnosis and stage (briefly, as in the medical report);
• previous and current treatment with dates;
• recent tests and reports (CT/MRI/PET, pathology) — when the coordinator asks, not in the first request;
• age, country of residence and ability to travel;
• the NCT number of this trial (filled in automatically when you apply from this page).

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT06895031 · JYP0015M101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗