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

Phase 1

Not yet recruiting

• Conditions: Solid Tumor; Pancreatic Ductal Adenocarcinoma (PDAC); Non-small Cell Lung Cancer (NSCLC); Colorectal Cancer (CRC)
• Interventions: Drug: JYP0015

• Registration Number: NCT06895031
• Lead Sponsor: Guangzhou JOYO Pharma Co., Ltd

Brief Summary

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.

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-19
• Study First Submitted QC: 2025-03-19
• Last Update Submitted: 2025-03-19
• Study First Posted: 2025-03-26
• Last Update Posted: 2025-03-26
• Study Start: 2025-03-27
• Primary Completion: 2026-03-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

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

Exclusion Criteria

1. Presence of central nervous system (CNS) metastases; however, subjects with previously treated brain metastases may be enrolled if clinically stable.
2. 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)
3. Congestive heart failure with New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) <50%.
4. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
JYP0015 in RAS-Mutant Solid Tumors	JYP0015	This arm includes participants with histologically or pathologically confirmed advanced solid tumors harboring RAS mutations, identified via molecular testing. RAS mutations are defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, 61, 117, or 146 (e.g., G12, G13, Q61, K117, or A146). Participants will receive JYP0015 as an oral tablet.

Primary Outcome Measures

Name	Time	Method
Number of Participants with Dose-Limiting Toxicity (DLT)	21 days	The number of participants experiencing dose-limiting toxicities (DLT) during the dose-escalation period of the study.
Incidence and Severity of Treatment-Emergent Adverse Events (AEs) and Serious AEs	Up to 3 years	The incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including abnormalities in laboratory values and vital signs.
Overall Response Rate (ORR)	Up to 3 years	Overall response rate assessed per RECIST v1.1 criteria.

Secondary Outcome Measures

Name	Time	Method
Time to Reach Maximum Blood Concentration (Tmax) of JYP0015	Up to 16 weeks	Time to reach maximum plasma concentration (Tmax) of JYP0015 following administration.
Duration of Response (DOR)	Up to 3 years	Duration of response as assessed by RECIST v1.1.
Time to Response (TTR)	Up to 3 years	Time to response as assessed by RECIST v1.1.
Maximum Observed Blood Concentration (Cmax) of JYP0015	Up to 16 weeks	Maximum plasma concentration (Cmax) of JYP0015 following administration.