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This is a Phase 1/2a, open-label, multi-center study of JAB-3068 in Patients with advanced solid tumors.This study has two phases: dose escalation phase and dose expansion phase.
Dose escalation study phase is designed to determine the maximum tolerated dose (MTD) according to a 3+3 design and recommended phase II dose (RP2D) and to characterize the safety, tolerability, and pharmacokinetics (PK) profile of JAB-3068. Other dose regimens may be explored based on the analysis of emerging PK and safety data. at this study phase, JAB-3068 dministered orally once daily (QD) or twice daily (BID) or once every other day (QOD) in 28-day treatment cycles to adult patients with advanced solid tumors,
Dose expansion study phase is designed to evaluate the antitumor activity(ORR and DOR) of JAB-3068 in patients with NSCLC, ESCC and HNSCC.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| JAB-3068 (SHP2 inhibitor) | Experimental | JAB-3068 will be administered orally in the morning following a fast of approximately 6 hours before on PK collection. Patients will continue to fast for approximately 2 hours after the administration of JAB-3068. On non-PK days patients will fast approximately 2 hours before JAB-3068 and continue to fast for approximately 2 hours afterwards. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| JAB-3068 | Drug | 25 mg,100 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with dose limiting toxicities | Number of participants with dose limiting toxicities (DLTs) in the dose escalation phase. A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle with JAB-3068. | At the end of Cycle 1 (each cycle is 28 days) |
| Objective response rate | ORR is defined as the proportion of participants with complete response or partial. the ORR of JAB-3068 in patients with ESCC, NSCLC and HNSCC will be evaluated separately in dose expansion | Approximately 2 years |
| Duration of response | DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first. The DOR of JAB-3068 in patients with ESCC, NSCLC and HNSCC will be evaluated separately in dose expansion | Approximately 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events | All patients participating in this study will be assessed for incidence and severity of adverse events (AEs) and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imaging and ophthalmological assessments | Approximately 2 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yuankai Shi, MD | Cancer Institute and Hospital, Chinese Academy of Medical Sciences | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cancer Hospital, Chinese Academy of Medical Sciences | Beijing | Beijing Municipality | 100021 | China | ||
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| Area under the curve |
Area under the plasma concentration time curve of JAB-3068 |
| Approximately 2 years |
| Cmax | Highest observed plasma concentration of JAB-3068 | Approximately 2 years |
| Tmax | Time of highest observed plasma concentration of JAB-3068 | Approximately 2 years |
| T1/2 | Half life of JAB-3068 | Approximately 2 years |
| Objective response rate | ORR is defined as the proportion of participants with complete response or partial response (CR+PR) in dose escalation. | Approximately 2 years |
| Duration of response | DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first in dose escalation. | Approximately 2 years |
| Peking Union Medical College Hospital |
| Beijing |
| Beijing Municipality |
| 100032 |
| China |
| Beijing Cancer Hospital | Beijing | Beijing Municipality | 100142 | China |
| Chinese PLA Central Hospital | Beijing | Beijing Municipality | 100853 | China |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D006258 | Head and Neck Neoplasms |
| D004938 | Esophageal Neoplasms |
| D009634 | Noonan Syndrome |
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D019465 | Craniofacial Abnormalities |
| D009139 | Musculoskeletal Abnormalities |
| D009140 | Musculoskeletal Diseases |
| D006330 | Heart Defects, Congenital |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D007414 | Intestinal Neoplasms |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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