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Evaluate the safety and antitumor activity of JYP0015 in adults with specific RAS mutant advanced solid tumors.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| JYP0015 in RAS-Mutant Solid Tumors | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JYP0015 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants with Dose-Limiting Toxicity (DLT) | The number of participants experiencing dose-limiting toxicities (DLT) during the dose-escalation period of the study. | 21 days |
| Incidence and Severity of Treatment-Emergent Adverse Events (AEs) and Serious AEs | The incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including abnormalities in laboratory values and vital signs. | Up to 3 years |
| Overall Response Rate (ORR) | Overall response rate assessed per RECIST v1.1 criteria. | Up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Blood Concentration (Cmax) of JYP0015 | Maximum plasma concentration (Cmax) of JYP0015 following administration. | Up to 16 weeks |
| Time to Reach Maximum Blood Concentration (Tmax) of JYP0015 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ling Shen, M.D. | Contact | 01088121122 | +86 | linshenpku@163.com |
| Xiao | Contact |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Recruiting | Beijing | Beijing Municipality | 100142 | China |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
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None (Open Label)
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Time to reach maximum plasma concentration (Tmax) of JYP0015 following administration.
| Up to 16 weeks |
| Duration of Response (DOR) | Duration of response as assessed by RECIST v1.1. | Up to 3 years |
| Time to Response (TTR) | Time to response as assessed by RECIST v1.1. | Up to 3 years |
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |