Clinical trial NCT06895031: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Pancreatic Ductal Adenocarcinoma (PDAC)
Non-small Cell Lung Cancer (NSCLC)
Colorectal Cancer (CRC)
Keywords: PDAC
NSCLC
CRC
Lead sponsor: Guangzhou JOYO Pharma Co., Ltd
Sponsor class: INDUSTRY
First posted: 2025-03-26
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: None (Open Label)
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Dose-Limiting Toxicity (DLT)
timeFrame: 21 days
measure: Incidence and Severity of Treatment-Emergent Adverse Events (AEs) and Serious AEs
timeFrame: Up to 3 years
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Maximum Observed Blood Concentration (Cmax) of JYP0015
timeFrame: Up to 16 weeks
measure: Time to Reach Maximum Blood Concentration (Tmax) of JYP0015
timeFrame: Up to 16 weeks
measure: Duration of Response (DOR)
timeFrame: Up to 3 years
measure: Time to Response (TTR)
timeFrame: Up to 3 years
Other outcomes:
Locations:
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