Colorectal Cancer (CRC), Non-small Cell Lung Cancer (NSCLC), Pancreatic Ductal Adenocarcinoma (PDAC), Solid Tumor
Conditions
Keywords
PDAC, NSCLC, CRC
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.
Interventions
DRUGJYP0015
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.
Sponsors
Guangzhou JOYO Pharma Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
None (Open Label)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Blood Concentration (Cmax) of JYP0015 | Up to 16 weeks | Maximum plasma concentration (Cmax) of JYP0015 following administration. |
| 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. |
Countries
China
Contacts
CONTACTLing Shen, M.D.
CONTACTXiao
Outcome results
None listed