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This is an open-label, dose escalation, multicenter, phase 1, first-in-human study of XNW28012 in subjects with advanced solid tumors who have failed current standard anti-tumor therapies or are intolerant to such therapies. The study consists of two parts: a dose escalation part and a dose expansion part.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bayesian Optimal Interval (BOIN) method will be used for the dose escalation part. | Other | Based on the toxicology data from preclinical studies, the Bayesian Optimal Interval (BOIN) method will be used for the dose escalation part with preset doses at 0.6 mg/kg, 1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg, 4.8 mg/kg, 6.0 mg/kg, and 7.5 mg/kg. Eligible subjects will receive XNW28012 every 3 weeks (Q3W) until intolerant toxicity, progression of disease with no clinical benefit, or withdrawal of informed consent. The first treatment cycle will be the dose limiting toxicity (DLT) assessment period. The safety, tolerability, and occurrence of DLTs will be assessed during the DLT period. The proposed dose escalation plan is shown below. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XNW28012 | Drug | Eligible subjects will receive XNW28012 every 3 weeks (Q3W) until intolerant toxicity, progression of disease with no clinical benefit, or withdrawal of informed consent. |
| Measure | Description | Time Frame |
|---|---|---|
| Ph 1: Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability]. | Incidence and severity of adverse events that are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. | through study completion, an average of 1 year |
| Ph 2: To evaluate the antitumor efficacy of XNW28012 at the recommended Part 2 dose. | ORR per RECIST1.1 assessed by Investigators. | through study completion, an average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Ph 1:Maximum tolerated dose (MTD) and/or the recommended Part 2 dose. | To determine the maximum tolerated dose (MTD) and the recommended Part 2 dose with XNW28012; | The first 21-day cycle of therapy |
| Ph 1/II: Maximum (peak) observed concentration (Cmax) of XNW28012. |
| Measure | Description | Time Frame |
|---|---|---|
| Ph 1/2: Tissue factor expression | Correlation between tissue factor expression and the antitumor efficacy of XNW28012. | At screening |
Inclusion Criteria:
Exclusion Criteria:
11. Clinically significant cardiovascular/cerebrovascular conditions. 12. Active ocular surface disease at screening, or subjects with any prior episode of cicatricial conjunctivitis.
13. Any history of Toxic Epidermal Necrolysis (TEN) or Steven Johnson Syndrome. 14. Subjects who have undergone major surgery within 28 days prior to the first dose of study drug, except if the procedure is minimally invasive (for example, introduction of peripherally inserted central catheter [PICC] line).
and so on.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yingjie zhao Yingjie Zhao | Contact | +86 15553136593 | yingjie.zhao@evopointbio.com | |
| Ziwen Ke | Contact | +86 15172466243 | ziwen.ke@evopointbio.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Second Affiliated Hospital of Anhui Medical University | Recruiting | Hefei | Anhui | China | ||
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Blood samples were collected at specified intervals for the determination of Cmax. |
| through study completion, an average of 1 year |
| Ph 1/II: Maximum (peak) observed concentration (Cmax) of total antibody of XNW28012.. | Blood samples were collected at specified intervals for the determination of Cmax. | through study completion, an average of 1 year |
| Ph 1/II: Maximum (peak) observed concentration (Cmax) of YL0010014 | Blood samples were collected at specified intervals for the determination of Cmax. | through study completion, an average of 1 year |
| Ph 1/II: Anti-drug antibody (ADA) | To assess the incidence of anti-drug antibody (ADA) against XNW28012 | through study completion, an average of 1 year |
| Ph I/II:Objective response rate (ORR) | ORR is defined as the proportion of subjects who have a confirmed CR or a PR per RECIST 1.1 assessed by Investigator. | Efficacy assessments will be performed at screening (≤ 28 days prior to the first dose), every 6 weeks for 24 weeks after the first dose, and every 12 weeks after the 24 weeks response assessments until disease progression (up to 1 year). |
| Ph I/II: Disease control rate (DCR) | Rate of complete response [CR], partial response [PR], and stable disease per RECIST1.1 assessed by Investigator. | Efficacy assessments will be performed at screening (≤ 28 days prior to the first dose), every 6 weeks for 24 weeks after the first dose, and every 12 weeks after the 24 weeks response assessments until disease progression (up to 1 year). |
| Ph I/II:Progression free survival (PFS) | Progression free survival (PFS) per RECIST1.1 assessed by Investigator | Efficacy assessments will be performed at screening (≤ 28 days prior to the first dose), every 6 weeks for 24 weeks after the first dose, and every 12 weeks after the 24 weeks response assessments until disease progression (up to 1 year). |
| Ph I/II: Duration of response (DOR) | Duration of response (DOR) per RECIST1.1 assessed by Investigator. | Efficacy assessments will be performed at screening (≤ 28 days prior to the first dose), every 6 weeks for 24 weeks after the first dose, and every 12 weeks after the 24 weeks response assessments until disease progression (up to 1 year). |
| The First Affiliated Hospital of University of Science and Technology of China |
| Recruiting |
| Hefei |
| Anhui |
| China |
| Beijing Friendship Hospital, Capital Medical University | Recruiting | Beijing | Beijing Municipality | China |
| Peking Union Medical College Hospital | Recruiting | Beijing | Beijing Municipality | China |
| Chongqing University Cancer Hospital | Recruiting | Chongqing | Chongqing Municipality | China |
| Fujian Provincial Cancer Hospital | Recruiting | Fuzhou | Fujian | China |
| Sun Yat-sen Memorial Hospital, Sun Yat-sen University | Recruiting | Guangzhou | Guangdong | China |
| Affiliated Hospital of Guizhou Medical University | Recruiting | Guiyang | Guizhou | China |
| Affiliated Hospital of Hebei University | Recruiting | Baoding | Hebei | China |
| Affiliated Cancer Hospital of Harbin Medical University | Recruiting | Harbin | Heilongjiang | China |
| First Affiliated Hospital of Henan University of Science and Technology | Recruiting | Luoyang | Henan | China |
| Hubei Cancer Hospital | Recruiting | Wuhan | Hubei | China |
| Hunan Cancer Hospital | Recruiting | Changsha | Hunan | China |
| The Second Xiangya Hospital Of Central South University | Recruiting | Changsha | Hunan | China |
| First Affiliated Hospital of Gannan Medical College | Recruiting | Ganzhou | Jiangxi | China |
| First Affiliated Hospital of Kunming Medical University | Recruiting | Yunnan | Kunming | China |
| Affiliated Hospital of Binzhou Medical College | Recruiting | Binzhou | Shandong | China |
| Jinan Central Hospital | Recruiting | Jinan | Shandong | China |
| Linyi Cancer Hospital | Recruiting | Linyi | Shandong | China |
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | Shanghai Municipality | China |
| Sichuan Provincial People's Hospital | Recruiting | Chengdu | Sichuan | China |
| West China Hospital of Sichuan University | Recruiting | Chengdu | Sichuan | China |
| Yunnan Cancer Hospital | Recruiting | Kunming | Yunnan | China |
| The First Affiliated Hospital of Zhejiang University School of Medicine | Recruiting | Hangzhou | Zhejiang | China |
| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| D010051 | Ovarian Neoplasms |
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D004066 | Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D006058 | Gonadal Disorders |
| D014594 | Uterine Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
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