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

NCT05627063 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ABSK121-NX-101
• Study Type: interventional
• Target: 169
• Locations: 2 countries
• Sites: 24

Brief Summary

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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Incidence of DLT

  dose-limiting toxicities (DLTs)

  At the end of Cycle 1 (each cycle is 28 days)

• Incidence and severity of adverse events (AEs)

  adverse events (AEs), adverse events of special interest (AESIs) and serious adverse events (SAEs)

  Through study completion, an average of half year

Secondary Outcomes (15)

• Cmax

  Through the study completion, an average of half year

• Tmax

  Through the study completion, an average of half year

• AUC

  Through the study completion, an average of half year

• t1/2

  Through the study completion, an average of half year

• Vz/F

  Through the study completion, an average of half year

Study Arms (1)

ABSK121-NX

EXPERIMENTAL

Dose escalation of oral ABSK121-NX will be guided by the Bayesian optimal interval (BOIN) design based on safety data collected until a maximum tolerated dose (MTD) or maximum administered dose (MAD) has been identified. Patients will receive a single dose of ABSK121-NX on Day -7 followed by a 7-day washout, as a run-in period to access the safety and PK of ABSK121-NX. Then, patients will continuously receive ABSK121-NX once daily (QD). The dose escalation will start at 3 mg QD followed by dose escalation of a total of 8 potential dose levels. Once RDE is determined, an RDE-confirmation group of up to 24 more patients may be enrolled at the selected dose levels to further evaluate safety and efficacy (up to 12 per dose level/regimen), if approved by the sponsor. In addition, a preliminary food-effect (FE) may be evaluated in at least 6 patients from the RDE- confirmation part. After the RDE is confirmed in the dose Escalation part, the dose Expansion phase will be conducted.

Drug: ABSK121-NX

Interventions

ABSK121-NX DRUG

In the escalation part, patients will receive a single dose of oral ABSK121-NX on Day -7 followed by a 7-day washout (Day -7 dosing day as 1st day of wash out) as a run-in period to access the safety and PK of ABSK121-NX. Then, patients will continuously receive ABSK121-NX once daily (QD) starting at C1D1 and continuing in subsequent cycles (28-day cycles). The starting dose is 3mg QD. In the expansion part, patients will each receive oral ABSK121-NX at the RDE in repeated 28-day cycles.

ABSK121-NX

Eligibility Criteria

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

You may qualify if:

• Patients should understand, sign, and date the written informed consent form prior to screening
• Male or female age 18 years or older
• 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
• For RDE-confirmation in the escalation part: patients with selected advanced solid tumors, i.e.,
• Patients must have the following FGFR genetic alterations based on central laboratory tests or existing test reports of tumor tissue and/or blood:
• Urothelial carcinoma (UC): pre-specified FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR2/3 fusions (partner gene is previously described or in frame), or
• Intrahepatic Cholangiocarcinoma (iCCA): 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)
• Patients must have at least one measurable target lesion according to RECIST 1.1
• For the expansion Part:
• \) Patients must have the following FGFR genetic alterations based on central laboratory tests or existing test reports of tumor tissue and/or blood:
• Urothelial carcinoma: pre-specified FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR2/3 fusions (partner gene is previously described or in frame)
• 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

You may not qualify if:

• Known allergy or hypersensitivity to any component of the investigational product
• RDE-confirmation in Escalation part: Prior treatment with any FGFR inhibitors
• Expansion part:
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• Previously FGFR-inhibitors naive cohorts in UC or iCCA patients: Prior treatment with any FGFR inhibitors
• Other solid tumors cohort: Prior treatment with any FGFR inhibitors
• \. Has a known additional malignancy that is progressing or has required active treatment.
• \. Has persistent phosphate level \>ULN during screening (within 14 days prior to the first dose of study treatment) and despite medical management
• \. Unable to swallow capsules or tablets or malabsorption syndrome, disease significantly affecting GI function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction. If any of these conditions exist, the site should discuss with the sponsor to determine patient eligibility
• \. Previous anti-cancer therapy, including chemotherapy (chemotherapy with nitrosourea or mitomycin received ≤ 6 weeks prior to initiation of study treatment), radiotherapy, molecular targeted therapy, antibody therapy or other investigational drugs received ≤4 weeks; endocrine therapy ≤2 weeks or ≤5 half-lives (whichever is shorter) prior to initiation of study treatment
• \. Major surgery within 4 weeks of the first dose of study drug. Note that all surgical wounds must be healed and free of infection or dehiscence
• \. Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies, including immunotherapy that have not regressed to Grade ≤1 severity (CTCAE v5.0) with the exception of alopecia, vitiligo and grade 2 peripheral neurotoxicity
• \. Potent inhibitors or inducers of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort). Refer to https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers for a list of drugs
• \. Active central nervous system (CNS) metastases including presence of cerebral edema, requirement for systemic steroid treatment, disease progression due to intracranial lesions, leptomeningeal metastasis, and other clinical symptoms related to CNS metastases
• \. Impaired cardiac function or clinically significant cardiac disease, including any one of the following:

Sponsors & Collaborators

• Abbisko Therapeutics Co, Ltd: lead

Study Sites (24)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89119, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Location

The First Affiliated Hospital of Henan University of Science & Technology

Luoyang, Henan, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Location

Hubei Cancer Hospital

Wuhan, Hubei, China

Location

Hunan Central Hospital

Changsha, Hunan, China

Location

The Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Location

Jilin Cancer Hospital

Changchun, Jilin, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, China

Location

Shanghai East Hospital Tongji University

Shanghai, Shanghai Municipality, China

Location

Shanxi Provincial Cancer Hospital

Taiyuan, Shanxi, China

Location

West China School of Medicine/West China Hospital of Sichuan University

Chengdu, Sichuan, China

Location

Mianyang Central Hospital

Mianyang, Sichuan, China

Location

Zhejiang University Cancer Hospital

Hangzhou, Zhejiang, China

Location

Fujian Cancer Hospital (Department of Hepatobiliary and Pancreatic Oncology /Phase I Ward)

Fuzhou, China

Location

Harbin Medical University Cancer Hospital (Gastroenterology Department 2nd Ward)

Haerbin, China

Location

Zhongshan Hospital of Fudan University (Hepatological Surgery Department)

Shanghai, China

Location

Zhongshan Hospital of Fudan University (Medical Oncology Department)

Shanghai, China

Location

Liaoning Cancer Hospital (Phase I Ward)

Shenyang, China

Location

Yantai Yuhuangding Hospital (Department of Medical Oncology, 1)

Yantai, China

Location

Study Officials

• Yuan Lu

  Wuxi Abbisko Biomedical Technology Co., Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: November 25, 2022
• Study Start: June 26, 2023
• Primary Completion: March 15, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: October 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CN (20)