Clinical trial NCT06799637: Study of XNW28012 in Subjects with Advanced Solid Tumors Who Failed Standard Treatments
Official title: A Phase 1, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Efficacy of XNW28012 in Subjects with Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Pancreatic Carcinoma
Ovarian Cancer
Cervical Cancers
Keywords: XNW28012
Lead sponsor: Evopoint Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2025-01-29
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. For the dose escalation part: subjects with histologically or cytologically confirmed advanced and/or metastatic solid tumors who have failed the established standard anti-cancer therapies for a given tumor type or have been intolerant to such therapies.
2. For the dose expansion part: subjects must have a histological or cytological diagnosis of progressive, locally advanced, and/or metastatic ovarian cancer, cervical cancer, pancreatic cancer, or colorectal cancer (CRC) who have failed the following anti-cancer therapies: Ovarian cancer, Cervical cancer, Pancreatic cancer, Colorectal cancer.
3. Age ≥ 18 years old at the time of consent.
4. Subjects must have at least 1 measurable lesion as defined per RECIST version 1.1 (for dose expansion part only).
5. Subjects must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. ECOG status of 2 can be allowed if it is a result of disease progression and warrants discussion with the medical monitor.
6. Subjects must have adequate organ function within 7 days prior to the first study drug administration, as indicated by the flaboratory values:
7. Life expectancy of at least 12 weeks.
8. Females of childbearing potential must have a negative pregnancy test within 7 days prior to the first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
9. Non-sterile subjects must be willing to use a highly effective contraception (e.g., IUD, pill, or condom) for the duration of the study and for 6 months after the last dose of study drug unless their partner is sterilized.
10. Subjects are able to provide written informed consent, understand and are willing to comply with the requirements of the study.

Exclusion Criteria:

1. A history of severe infusion reactions to other monoclonal antibodies/antibody drug conjugates (ADCs) or allergic reactions to any components of XNW28012.
2. Any anti-tumor therapy within 28 days prior to the first dose, including but not limited to: small molecules, immunotherapy, chemotherapy, monoclonal antibodies, or any other experimental drugs.
3. Any active malignancy, with the exception of the specific types of cancers under investigation in this study and any locally recurring cancer that has been treated curatively .
4. Have received a live vaccine within 4 weeks prior to the first dose of study drug. Note: Seasonal vaccines for influenza are generally inactivated vaccines and are allowed; however, intranasal influenza vaccines will not be allowed if they are attenuated live vaccines.
5. Have received granulocyte colony stimulating factor (G-CSF) or granulocyte / macrophage colony stimulating factor support within 1 week before screening, or pegylated G-CSF within 2 weeks before screening.
6. Subjects with toxicities (as a result of prior anti-cancer therapy) which have not improved to CTCAE grade ≤1 or stabilized, except those AEs not considered as a likely safety risk (e.g., alopecia).
7. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or stroke (transient ischemic attack) ≤ 3 months prior to screening is allowed if stable.
8. Any of the hematological risk factors:
9. Subjects who are unwilling or unable to provide tumor tissue samples that meet the requirements for tissue factor (TF) expression testing.

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.

Primary outcomes:
measure: Ph 1: Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability].
timeFrame: through study completion, an average of 1 year
measure: Ph 2: To evaluate the antitumor efficacy of XNW28012 at the recommended Part 2 dose.
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Ph 1:Maximum tolerated dose (MTD) and/or the recommended Part 2 dose.
timeFrame: The first 21-day cycle of therapy
measure: Ph 1/II: Maximum (peak) observed concentration (Cmax) of XNW28012.
timeFrame: through study completion, an average of 1 year
measure: Ph 1/II: Maximum (peak) observed concentration (Cmax) of total antibody of XNW28012..
timeFrame: through study completion, an average of 1 year
measure: Ph 1/II: Maximum (peak) observed concentration (Cmax) of YL0010014
timeFrame: through study completion, an average of 1 year
measure: Ph 1/II: Anti-drug antibody (ADA)
timeFrame: through study completion, an average of 1 year
measure: Ph I/II：Objective response rate (ORR)
timeFrame: 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).
measure: Ph I/II: Disease control rate (DCR)
timeFrame: 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).
measure: Ph I/II：Progression free survival (PFS)
timeFrame: 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).
measure: Ph I/II: Duration of response (DOR)
timeFrame: 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).
Other outcomes:
measure: Ph 1/2: Tissue factor expression
timeFrame: At screening
Locations:
city: Hefei
country: China
facility: Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of University of Science and Technology of China
state: Anhui
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Guiyang
country: China
facility: Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Luoyang
country: China
facility: First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital Of Central South University
state: Hunan
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical College
state: Jiangxi
city: Yunnan
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Kunming
city: Binzhou
country: China
facility: Affiliated Hospital of Binzhou Medical College
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: