XNW27011 Study of Advanced Solid Tumor Subjects Who Failed Standard Therapies.

NCT06792435 | Recruiting Phase 1 DMC

• 1 other identifier: XNW27011-I/II-01
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

This is a global, multi-center, open-label, Phase I/II first-in-human study of XNW27011 monotherapy as an investigational product (IP) in patients with locally advanced and/or metastatic solid tumors who have failed or are intolerant to standard therapies. XNW27011 is an antibody-drug conjugate (ADC) targeting Claudin 18.2 (CLDN18.2), a transmembrane protein important to tight junctions. The study consists of 2 parts: Part 1 is the dose-escalation phase (Phase I), and Part 2 is the does-expansion phase (Phase II). In phase I part of the study, approximately 42 patients with locally advanced and/or metastatic solid tumors will be enrolled, irrespective of CLDN18.2 expression. However, the most recently available tumor tissue specimen will be collected (if available) for a retrospective CLDN18.2 expression confirmation. In phase II part of the study, only patients with confirmed CLDN18.2 expression by IHC in the central laboratory will be enrolled.The phase II part of the study will consist of the following four groups，Up to three dose cohorts for each patient group are planned currently. Each dose cohort will include approximately 20 patients. Approximately 240 patients evaluable will be enrolled in Phase Ⅱ part of the study.

Conditions

Pancreatic Adenocarcinoma Metastatic; Lung Cancer (NSCLC); Ovarian Cancer; Colorectal Cancer Metastatic; Biliary Tract Cancer; Gastric Carcinoma; Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Phase I (Dose Escalation):To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of XNW27011

  In the dose escalation phase, if there are ≥ 2 cases of DLT among 3-6 subjects at a dose level during the DLT observation period (Cycle 1, 21days), the previous dose or intermediate dose (the midway dose between the previous dose group and the intolerant dose group) may be defined as MTD.

  Baseline up to approximately 2 years

• Phase Ⅱ (Dose Expansion):To evaluate the objective response rate (ORR) of XNW27011 by cohorts at RP2D. The objective response includes the complete response (CR) and the partial response (PR).

  To evaluate the objective response rate (ORR) of XNW27011 by cohorts at RP2D. The objective response includes the complete response (CR) and the partial response (PR).

  Baseline up to approximately 2 years

Secondary Outcomes (14)

• Phase I (Dose Escalation):To assess the dose limiting toxicities (DLTs) of XNW27011 when administered intravenously (IV) as a monotherapy during the first cycle (3 weeks [21 days]) to patients with locally advanced and/or metastatic solid tumors.

  3 weeks

• Phase I (Dose Escalation)：To assess the overall safety of XNW27011 when administered IV as a monotherapy every cycle (3 weeks [Q3W]) to patients with locally advanced and/or metastatic solid tumors.

  3 weeks

• Phase I (Dose Escalation)：To assess the pharmacokinetic (PK) profiles of XNW27011, total antibody (XNW27011-TAb, including conjugated and unconjugated), the topoisomerase I inhibitor YL0010014 (payload/toxin) and the major metabolites.

  Baseline up to approximately 2 years

• Phase I (Dose Escalation)：To evaluate the preliminary efficacy of XNW27011 as a monotherapy.

  Baseline up to approximately 2 years

• Phase I (Dose Escalation)：To assess the incidence of anti-drug antibody (ADA) against XNW27011.

  Baseline up to approximately 2 years

Study Arms (2)

Phase I Dose Escalation

EXPERIMENTAL

Based on the preclinical data of XNW27011, the dose-escalation study will start from the initial dose of 0.6 mg/kg. Dose escalation will be performed by using a modified Fibonacci method with a slightly fine-tuned dose escalation amplitude. The first two dose escalations will be by 100% of the preceding dose and thereafter by 50%, 33%, 25% and 25% of the preceding doses. Therefore, there are 7 dose cohorts for projected dose escalations as follows

Drug: XNW27011

Phase II: Expanded cohorts

EXPERIMENTAL

The SRC will select up to 3 recommended doses for Phase II study based on the safety, PK, ADA and preliminary efficacy data from Phase I study (dose escalation). Phase Ⅱwill include 4 patient groups, and up to 3 dose cohorts for each patient group. Approximately 20 Chinese or U.S. patients will be enrolled to each dose cohort with an approximately total of 240 patients in the Phase II study to further evaluate the antitumor activity, safety, tolerability, PK and incidence of ADA for XNW27011.

Drug: XNW27011

Interventions

XNW27011 DRUG

Eligible patient(s) in each dose cohort will receive the assigned XNW27011 dose administration every 3 weeks (Q3W, cycle) until intolerable toxicity, progression of the disease without clinical benefit, or withdrawal of informed consent. An accelerated titration scheme will be used for the first two dose levels (0.6 mg/kg and 1.2 mg/kg) starting from 0.6 mg/kg dose as follows: The first patient will be enrolled for 0.6 mg/kg dose. If the subject shows no significant toxicity in cycle 1 (DLT observation period), the second patient will be enrolled for 1.2 mg/kg. 3 + 3 dose escalation:3 patients will be enrolled to the dose cohort first，If 1 of 3 patients experiences a DLT, up to 3 more patients will be enrolled in the same dose cohort.. If none of the additional 3 patients experiences a DLT, dose escalation will continue to the next dose.Dose escalation will be stopped when 2 or more patients out of 3 to 6 patients at the same dose level experience a DLT.

Phase I Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase I (Dose Escalation)：
• Patients are willing and able to provide written informed consent or where consent is provided by legally authorized representatives.
• Age ≥18 years old when signing the informed consent form.
• Patients with a histologically or cytologically-confirmed, locally advanced or metastatic solid tumor, which has failed on standard therapy or is intolerable to available standard therapy, or there is no available standard therapy for the tumor. The advanced solid tumors include but are not limited to gastric and gastroesophageal junction adenocarcinoma, pancreatic adenocarcinoma, esophageal adenocarcinoma, ovarian cancer, lung cancer, colorectal cancer, andbiliary tract cancer.
• The enrollment is not restricted to patients with tumor expressing CLDN18.2. However patients are required to provide tumor tissue sections for CLDN18.2 expression confirmation.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Estimated life expectancy \> 12 weeks.
• At least one measurable cancer lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).
• Adequate organ function, evidenced by the following laboratory results:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
• Platelet count ≥ 100 × 109/L.
• Hemoglobin ≥ 9.0 g/dL.
• Total bilirubin ≤ 1.5 × the upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × ULN (if liver metastases are present, ≤ 3 × ULN).
• Creatinine clearance (Ccr) ≥60 mL/minute as calculated using themodified Cockcroft-Gault equation.

You may not qualify if:

• PHASE I (DOSE ESCALATION)：
• Prior severe allergic reaction or intolerance to a monoclonal antibody, including humanized or chimeric antibodies.
• Prior severe allergic reaction or intolerance to the Topoisomerase I Inhibitor or Topoisomerase Inhibitor-Based ADC (e.g: Fam-trastuzumab deruxtecan-nxki, Sacituzumab govitecan-hziy, Irinotecan, Topotecan) or any excipient in the XNW27011 formulation.
• Having any of the following medical conditions in the past or at present:
• Acquired or congenital immunodeficiency diseases or organ transplantation.
• Past myocardial infarction (within 6 months before the first administration), hospitalization for congestive heart failure within 12 months before the first administration, severe or unstable angina, coronary or peripheral artery bypass grafting, New York Heart Association (NYHA) grade Ⅲ or IV heart failure, uncontrollable hypertension (Systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg at rest).
• Concomitant diseases that will seriously endanger the safety of the subject or affect the completion of the tests, such as active gastrointestinal bleeding, active peptic ulcer, intestinal obstruction, intestinal paralysis, interstitial pneumonia, lung fibrosis, kidney failure, and uncontrolled diabetes(HbA1c\>8%).
• History of or currently suffering from uncontrolled primary or metastasized brain tumors, except that the investigator believes that the disease has been stabilized in patients, or whose local treatment has ended.
• History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of the XNW27011.
• Past or current mental illness that is difficult to control.
• Human immunodeficiency virus (HIV) infection, syphilis infection, or active hepatitis B or C infection. Note: Syphilis infection refers to active syphilis or latent syphilis that requires treatment.
• Patients who have active infections that required systemic treatment within 2 weeks prior to the first dose of XNW27011.
• Clinically significant third spacing (large amount of pleural fluid or ascites, judged by treating physician) that is uncontrollable by drainage or other methods.
• Having any adverse event from prior anti-tumor treatments that have not yet recovered to Grade 0 or 1 per NCI-CTCAE v5.0 (except alopecia).
• History of treatment:

Sponsors & Collaborators

• Evopoint Biosciences Inc.: lead

Study Sites (1)

Affiliated Hospital of Shandong First Medical University

Jinan, Shandong, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Biliary Tract Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Digestive System Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases

Central Study Contacts

Yingjie Zhao

CONTACT

+86 15172466243; yingjie.zhao@evopointbio.com

zhenhao Ma

CONTACT

+86 13325139290; zhenhao.ma@evopointbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 25, 2024
• First Posted: January 24, 2025
• Study Start: July 27, 2023
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: February 7, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)