ACTIVE_NOT_RECRUITING

A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK121-NX in Patients With Advanced Solid Tumors

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open-label phase 1 study with expansion. The study will start with a dose escalation of single-agent ABSK121-NX administered in repeated 28-day cycles in patients with advanced solid tumors to evaluate safety and tolerability. The expansion part will investigate oral ABSK121-NX at the recommended dose for expansion (RDE) to further evaluate safety and tolerability among selected tumor types. Preliminary antitumor activity will also be assessed.

Official Title

A Phase 1, Open-Label Study of ABSK121-NX to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Solid Tumors

Quick Facts

Study Start:2023-06-26

Study Completion:2026-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05627063

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patients should understand, sign, and date the written informed consent form prior to screening 2. Male or female age 18 years or older 3. Patients with histologically confirmed locally-advanced or metastatic solid tumors who have progressed on, or are intolerant of standard therapy, or for whom no standard therapy exists, or reject standard therapy 1. Patients must have the following FGFR genetic alterations based on central laboratory tests or existing test reports of tumor tissue and/or blood: 1. Urothelial carcinoma (UC): pre-specified FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR2/3 fusions (partner gene is previously described or in frame), or 2. Intrahepatic Cholangiocarcinoma (iCCA): FGFR2 fusions or rearrangements which containing an intact kinase domain as follows: 2. Patients must have at least one measurable target lesion according to RECIST 1.1 1. Urothelial carcinoma: pre-specified FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR2/3 fusions (partner gene is previously described or in frame) 2. Cholangiocarcinoma: FGFR2 fusions or rearrangements which containing an intact kinase domain as follows: * FGFR2 fusions: FGFR2 rearrangements with a literature-derived known partner gene regardless of strand or frame, or FGFR2 rearrangements in the same 5' to 3' orientation and in frame with a novel partner gene * FGFR2 rearrangements: FGFR2 rearrangements with one breakpoint in the hotspot region (intron 17-exon 18) and the other breakpoint in an intergenic region or within another gene, or intragenic duplication of the kinase domain (exon 9-17) 3. Other tumor types: solid tumors harboring FGFR1-4 alterations including activating mutations, fusions or rearrangements and amplifications, e.g., advanced/metastatic gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma harboring the FGFR2 amplifications, or iCCA patients or UC patients with other FGFR alterations not mentioned above, are also allowed 1. Absolute neutrophil count (ANC) ≥1.5×109/L (without the use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF) within 7 days before testing) 2. Platelet count (PLT) ≥100×109/L (without transfusion within 14 days before testing) 3. Hemoglobin (Hb) ≥90 g/L (without transfusion within 7 days before testing) 4. Total bilirubin (TBIL) ≤1×ULN 5. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5×ULN 6. Creatinine clearance (Crcl) ≥60 mL/min based on Cockcroft-Gault formula 7. Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits, sodium ≥130 mmol/L, potassium within institutional normal limits 7. For patients participating exploration of food effect: 1. be able to eat a standardized high-fat, high caloric meal within 30 minutes 2. be able to fast for 10 hours	1. Known allergy or hypersensitivity to any component of the investigational product 2. RDE-confirmation in Escalation part: Prior treatment with any FGFR inhibitors 3. Expansion part: 1. Previously FGFR-inhibitors naive cohorts in UC or iCCA patients: Prior treatment with any FGFR inhibitors 2. Other solid tumors cohort: Prior treatment with any FGFR inhibitors 1. New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure, 2. Baseline prolongation of the rate-corrected QT interval based on repeated demonstration of QTcF \>470 ms (average of screening triplicates) or history of long QT interval corrected (QTc) syndrome (Note: QTc interval corrected by Fridericia's formula), 3. Left ventricular ejection fraction (LVEF) \<50% or below the institutional lower limit of normal (whichever is higher) 1. Active hepatitis B infection: positive tests for hepatitis B surface antigen (HBsAg), or antibody to hepatitis B core antigen (anti-HBc). A patient with positive tests for HBsAg or anti-HBc but with HBV-DNA measurements lower than detectable (or per local practice) can be enrolled, 2. Active hepatitis C infection: positive Hepatitis C virus antibody. If positive antibody to hepatitis C Virus (anti-HCV) is detected, Hepatitis C virus RNA by polymerase chain reaction (PCR) is necessary. A patient with positive anti-HCV but with a negative test for HCV RNA can be enrolled 1. Current evidence or previous history of retinal pigment epithelial detachment (RPED) /Central serous retinopathy (CSR) 2. Previous laser treatment or intra-ocular injection for treatment of macular degeneration 3. Current evidence or previous history of dry or wet age-related macular degeneration 4. Current evidence or previous history of retinal vein occlusion (RVO) 5. Current evidence or previous history of retinal degenerative diseases (e.g., hereditary) 6. Diabetic retinopathy with macular edema 7. Current evidence or previous history of any other clinically relevant chorioretinal defect 8. Uncontrolled glaucoma or intraocular pressure \> 21 mmHg \[after intervention per local standard of care (SOC)\] 9. History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids 10. Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks prior to first dose) or actively progressing 11. Current evidence or previous history of corneal pathology such as keratopathy, corneal abrasion or ulceration, or current evidence of conjunctivitis

Inclusion Criteria

Exclusion Criteria

1. Patients should understand, sign, and date the written informed consent form prior to screening
2. Male or female age 18 years or older
3. Patients with histologically confirmed locally-advanced or metastatic solid tumors who have progressed on, or are intolerant of standard therapy, or for whom no standard therapy exists, or reject standard therapy
1. Patients must have the following FGFR genetic alterations based on central laboratory tests or existing test reports of tumor tissue and/or blood:
1. Urothelial carcinoma (UC): pre-specified FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR2/3 fusions (partner gene is previously described or in frame), or
2. Intrahepatic Cholangiocarcinoma (iCCA): FGFR2 fusions or rearrangements which containing an intact kinase domain as follows:
2. Patients must have at least one measurable target lesion according to RECIST 1.1
1. Urothelial carcinoma: pre-specified FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR2/3 fusions (partner gene is previously described or in frame)
2. Cholangiocarcinoma: FGFR2 fusions or rearrangements which containing an intact kinase domain as follows:
* FGFR2 fusions: FGFR2 rearrangements with a literature-derived known partner gene regardless of strand or frame, or FGFR2 rearrangements in the same 5' to 3' orientation and in frame with a novel partner gene
* FGFR2 rearrangements: FGFR2 rearrangements with one breakpoint in the hotspot region (intron 17-exon 18) and the other breakpoint in an intergenic region or within another gene, or intragenic duplication of the kinase domain (exon 9-17)
3. Other tumor types: solid tumors harboring FGFR1-4 alterations including activating mutations, fusions or rearrangements and amplifications, e.g., advanced/metastatic gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma harboring the FGFR2 amplifications, or iCCA patients or UC patients with other FGFR alterations not mentioned above, are also allowed
1. Absolute neutrophil count (ANC) ≥1.5×109/L (without the use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF) within 7 days before testing)
2. Platelet count (PLT) ≥100×109/L (without transfusion within 14 days before testing)
3. Hemoglobin (Hb) ≥90 g/L (without transfusion within 7 days before testing)
4. Total bilirubin (TBIL) ≤1×ULN
5. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5×ULN
6. Creatinine clearance (Crcl) ≥60 mL/min based on Cockcroft-Gault formula
7. Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits, sodium ≥130 mmol/L, potassium within institutional normal limits 7. For patients participating exploration of food effect:
1. be able to eat a standardized high-fat, high caloric meal within 30 minutes
2. be able to fast for 10 hours

1. Known allergy or hypersensitivity to any component of the investigational product
2. RDE-confirmation in Escalation part: Prior treatment with any FGFR inhibitors
3. Expansion part:
1. Previously FGFR-inhibitors naive cohorts in UC or iCCA patients: Prior treatment with any FGFR inhibitors
2. Other solid tumors cohort: Prior treatment with any FGFR inhibitors
1. New York Heart Association class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension or congestive heart failure,
2. Baseline prolongation of the rate-corrected QT interval based on repeated demonstration of QTcF \>470 ms (average of screening triplicates) or history of long QT interval corrected (QTc) syndrome (Note: QTc interval corrected by Fridericia's formula),
3. Left ventricular ejection fraction (LVEF) \<50% or below the institutional lower limit of normal (whichever is higher)
1. Active hepatitis B infection: positive tests for hepatitis B surface antigen (HBsAg), or antibody to hepatitis B core antigen (anti-HBc). A patient with positive tests for HBsAg or anti-HBc but with HBV-DNA measurements lower than detectable (or per local practice) can be enrolled,
2. Active hepatitis C infection: positive Hepatitis C virus antibody. If positive antibody to hepatitis C Virus (anti-HCV) is detected, Hepatitis C virus RNA by polymerase chain reaction (PCR) is necessary. A patient with positive anti-HCV but with a negative test for HCV RNA can be enrolled
1. Current evidence or previous history of retinal pigment epithelial detachment (RPED) /Central serous retinopathy (CSR)
2. Previous laser treatment or intra-ocular injection for treatment of macular degeneration
3. Current evidence or previous history of dry or wet age-related macular degeneration
4. Current evidence or previous history of retinal vein occlusion (RVO)
5. Current evidence or previous history of retinal degenerative diseases (e.g., hereditary)
6. Diabetic retinopathy with macular edema
7. Current evidence or previous history of any other clinically relevant chorioretinal defect
8. Uncontrolled glaucoma or intraocular pressure \> 21 mmHg \[after intervention per local standard of care (SOC)\]
9. History of systemic disease or ophthalmologic disorders requiring chronic use of ophthalmic steroids
10. Evidence of any ongoing ophthalmologic abnormalities or symptoms that are acute (within 4 weeks prior to first dose) or actively progressing
11. Current evidence or previous history of corneal pathology such as keratopathy, corneal abrasion or ulceration, or current evidence of conjunctivitis

Contacts and Locations

Principal Investigator

Yuan Lu

STUDY_DIRECTOR

Wuxi Abbisko Biomedical Technology Co., Ltd.

Study Locations (Sites)

UC San Diego Moores Cancer Center

La Jolla, California, 92093

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89119

United States

Gabrail Cancer Center Research

Canton, Ohio, 44718

United States

Collaborators and Investigators

Sponsor: Abbisko Therapeutics Co, Ltd

Yuan Lu, STUDY_DIRECTOR, Wuxi Abbisko Biomedical Technology Co., Ltd.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-26

Study Completion Date2026-06-30

Study Record Updates

Study Start Date2023-06-26

Study Completion Date2026-06-30

Terms related to this study

Additional Relevant MeSH Terms

Solid Tumor