Study of XNW28012 in Subjects with Advanced Solid Tumors Who Failed Standard Treatments

Phase 1

Recruiting

• Conditions: Advanced Solid Tumors; Pancreatic Carcinoma; Ovarian Cancer; Cervical Cancers
• Interventions: Drug: XNW28012

• Registration Number: NCT06799637
• Lead Sponsor: Evopoint Biosciences Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-01
• Status Verified: 2024-12
• Study First Submitted: 2024-12-25
• Study First Submitted QC: 2025-01-23
• Study First Posted: 2025-01-29
• Last Update Submitted: 2025-03-11
• Last Update Posted: 2025-03-13
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

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.

10. Clinically significant cardiovascular/cerebrovascular conditions. 12. Active ocular surface disease at screening, or subjects with any prior episode of cicatricial conjunctivitis.

11. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bayesian Optimal Interval (BOIN) method will be used for the dose escalation part.	XNW28012	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.

Primary Outcome Measures

Name	Time	Method
Ph 1: Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability].	through study completion, an average of 1 year	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.
Ph 2: To evaluate the antitumor efficacy of XNW28012 at the recommended Part 2 dose.	through study completion, an average of 1 year	ORR per RECIST1.1 assessed by Investigators.

Secondary Outcome Measures

Name	Time	Method
Ph 1:Maximum tolerated dose (MTD) and/or the recommended Part 2 dose.	The first 21-day cycle of therapy	To determine the maximum tolerated dose (MTD) and the recommended Part 2 dose with XNW28012;
Ph 1/II: Maximum (peak) observed concentration (Cmax) of total antibody of XNW28012..	through study completion, an average of 1 year	Blood samples were collected at specified intervals for the determination of Cmax.
Ph 1/II: Maximum (peak) observed concentration (Cmax) of YL0010014	through study completion, an average of 1 year	Blood samples were collected at specified intervals for the determination of Cmax.
Ph 1/II: Maximum (peak) observed concentration (Cmax) of XNW28012.	through study completion, an average of 1 year	Blood samples were collected at specified intervals for the determination of Cmax.
Ph 1/II: Anti-drug antibody (ADA)	through study completion, an average of 1 year	To assess the incidence of anti-drug antibody (ADA) against XNW28012
Ph I/II：Progression free survival (PFS)	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).	Progression free survival (PFS) per RECIST1.1 assessed by Investigator
Ph I/II: Duration of response (DOR)	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).	Duration of response (DOR) per RECIST1.1 assessed by Investigator.
Ph I/II：Objective response rate (ORR)	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).	ORR is defined as the proportion of subjects who have a confirmed CR or a PR per RECIST 1.1 assessed by Investigator.
Ph I/II: Disease control rate (DCR)	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).	Rate of complete response \[CR\], partial response \[PR\], and stable disease per RECIST1.1 assessed by Investigator.

Trial Locations

Locations (24)

Second Affiliated Hospital of Anhui Medical University; 🇨🇳 Hefei, Anhui, China

The First Affiliated Hospital of University of Science and Technology of China; 🇨🇳 Hefei, Anhui, China

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China

Chongqing University Cancer Hospital; 🇨🇳 Chongqing, Chongqing, China

Fujian Provincial Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Affiliated Hospital of Guizhou Medical University; 🇨🇳 Guiyang, Guizhou, China

Affiliated Hospital of Hebei University; 🇨🇳 Baoding, Hebei, China

Affiliated Cancer Hospital of Harbin Medical University; 🇨🇳 Harbin, Heilongjiang, China

First Affiliated Hospital of Henan University of Science and Technology; 🇨🇳 Luoyang, Henan, China

Hubei Cancer Hospital; 🇨🇳 Wuhan, Hubei, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

The Second Xiangya Hospital Of Central South University; 🇨🇳 Changsha, Hunan, China

First Affiliated Hospital of Gannan Medical College; 🇨🇳 Ganzhou, Jiangxi, China

First Affiliated Hospital of Kunming Medical University; 🇨🇳 Yunnan, Kunming, China

Affiliated Hospital of Binzhou Medical College; 🇨🇳 Binzhou, Shandong, China

Jinan Central Hospital; 🇨🇳 Jinan, Shandong, China

Linyi Cancer Hospital; 🇨🇳 Linyi, Shandong, China

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China

Sichuan Provincial People's Hospital; 🇨🇳 Chengdu, Sichuan, China

West China Hospital of Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Yunnan Cancer Hospital; 🇨🇳 Kunming, Yunnan, China

The First Affiliated Hospital of Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China