Assessing the safety and tolerability of ABSK061 in patients with advanced solid tumors

A Phase 1, Open-Label Study of ABSK061 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Solid Tumors

This study is testing a new drug called ABSK061 to see if it's safe and how well it works for people with advanced solid tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 85 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Abbisko Therapeutics Co, Ltd (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 22 sites (Dallas, Texas and 21 other locations)
• Trial ID: NCT05244551 on ClinicalTrials.gov

What this trial studies

This open-label phase 1 study evaluates the safety, tolerability, and pharmacokinetics of ABSK061 in patients with advanced solid tumors. The study consists of a dose escalation phase, where patients receive escalating doses of ABSK061 to determine the maximum tolerated dose, followed by an expansion phase that focuses on specific tumor types. Patients will be monitored for safety and preliminary antitumor activity throughout the study. The design incorporates a Bayesian optimal interval approach to guide dosing decisions based on safety data.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed solid tumors that have progressed on or are intolerant to standard therapies.

Not a fit: Patients with solid tumors for which effective standard therapies exist or those without the required FGFR2/3 genetic alterations may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors who have limited or no effective therapies available.

How similar studies have performed: While this approach is novel in its specific application, similar studies targeting advanced solid tumors have shown promise in evaluating new therapies.

Eligibility criteria

Inclusion Criteria:

1. Patient should understand, sign, and date the written informed consent form prior to screening.
2. Male or female age 18 years or older.
3. For escalation part: patients with histologically confirmed solid tumors who have progressed on or are intolerant of standard therapy or for whom no standard therapy exists.

For expansion Part:

1. Patients with histologically confirmed urothelial carcinoma or cholangiocarcinoma who have progressed on or are intolerant of standard therapy or for whom no standard therapy exists.
2. Patients must have tumors with following FGFR2/3 genetic alterations based on central laboratory test or existing test reports: Urothelial carcinoma: FGFR2/3 fusions and FGFR3 activating mutations Cholangiocarcinoma: FGFR2 fusions and/or arrangements
3. Patients must have at least one measurable target lesion according to RECIST 1.1.
4. Patients are willing to undergo biopsy if archival tumor tissue is not available or the archival specimen deemed inadequate or confirmed FGFR2/3 alterations from existing reports is not available.

4\. ECOG performance status 0 or 1 5. Life expectancy ≥3 months 6. Adequate organ function and bone marrow function as indicated by the following screening assessments performed within 14 days prior to the first dose of study drug:

1. Absolute neutrophil count (ANC) ≥1.5×109/L
2. Platelet count (PLT) ≥ 100×109/L without transfusion requirement within 14 days before 1st dose
3. Hemoglobin (Hb)≥90 g/L
4. Total bilirubin (TBIL) ≤1×ULN
5. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5×ULN.
6. Serum creatinine (Cr) of ≤1.5×ULN for the reference laboratory or creatinine clearance (Crcl) ≥ 50 mL/min based on Cockcroft-Gault formula

Exclusion Criteria:

1. Known allergy or hypersensitivity to any component of the investigational product
2. For expansion part only: Previous treatment with FGFR pathway inhibitors or multi-kinase inhibitors which target FGFR inhibition (recommend to consult with sponsor)
3. Has a known additional malignancy that is progressing or has required active treatment.
4. Inability to take oral medication or significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption of oral medication
5. Previous anti-cancer therapy, including chemotherapy (chemotherapy with nitrosourea or mitomycin should be at least 6 weeks prior to initiation of study treatment), radiotherapy, molecular targeted therapy or other investigational drugs received ≤4 weeks; endocrine therapy ≤2 weeks or ≤5-half life (whichever is shorter) prior to initiation of study treatment.
6. 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.
7. 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 and vitiligo.
8. Concomitant use of the drugs/remedies that may cause pharmacokinetic drug-drug interactions; consumption of grapefruit juice, grapefruit hybrids, pomegranates, starfruit, pomelos, Seville oranges or juice products within 7 days prior to the first dose of study medication.
9. 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.
10. Impaired cardiac function or clinically significant cardiac disease, including any one of the following:

    * 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
    * Baseline prolongation of the rate-corrected QT interval based on repeated demonstration of QTcF \>470 ms or history of long QT interval corrected (QTc) syndrome (Note: QTc interval corrected by Fridericia's formula).
    * Left ventricular ejection fraction (LVEF) \<50% or below the institutional lower limit of normal (whichever is higher)
11. Known human immunodeficiency virus (HIV) or active hepatitis B, or active hepatitis C infection; positive tests for hepatitis B virus surface antigen (HBsAg), or antibody to hepatitis B core Ag (HBcAb), or hepatitis C RNA in serum (subjects with history of hepatitis C infection but negative hepatitis C virus polymerase chain reaction (PCR) test are allowed; positive tests for HBV HBsAg or HBcAb with HBV-DNA measurements lower than 1000IU/ml can be included)
12. Any of the following ophthalmological criteria:

    * Current evidence or previous history of retinal pigmented epithelial detachment (RPED)
    * Previous laser treatment or intra-ocular injection for treatment of macular degeneration
    * Current evidence or previous history of dry or wet age-related macular degeneration
    * Current evidence or previous history of retinal vein occlusion (RVO)
    * Current evidence or previous history of retinal degenerative diseases (eg, hereditary)
    * Current evidence or previous history of any other clinically relevant chorioretinal defect
    * Current evidence or previous history of corneal pathology such as conjunctivitis, keratopathy, corneal abrasion or ulceration
13. Patients with refractory/uncontrolled ascites or pleural effusion.
14. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test within 7 days prior to the start of study drug.
15. Non-surgically sterilized male or female patients of childbearing potential must agree to use highly effective methods of birth control during the study and for up to 6 months after the last dose of study drug.
16. Sexually active males, unless they use a condom during intercourse while taking drug and for 5 consecutive compound half-lives plus 60 days after stopping study drug, should not father a child. A condom is required to be used also by vasectomized men to prevent delivery of the drug via seminal fluid.
17. Vaccination with a live, attenuated vaccine within 4 weeks of the first dose of study treatment and while on trial is prohibited except for administration of inactivate vaccines (e.g., COVID-19 vaccines, inactivated influenza vaccines).
18. Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.

Where this trial is running

Dallas, Texas and 21 other locations

• Mary Crowley Cancer Research — Dallas, Texas, United States (Recruiting)
• Yuan LU — Shanghai, Abbisko Therapeutics Co., Ltd. 12B Floor, Building 1, Lane 515, China (Recruiting)
• The First Affiliated Hospital of Bengbu Medical College — Bengbu, Anhui, China (Recruiting)
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Chongqing Daping Hospital — Chongqing, Chongqing Municipality, China (Not_yet_recruiting)
• Fujian Cancer Hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• Zhejiang Cancer Hospital — Hangzhou, Gongshu District, China (Recruiting)
• Sun Yat-sen Memorial Hospital/ the Second Affiliated Hospital of Sun Yat-sen University — Guanzhou, Guangdong, China (Recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Not_yet_recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (Recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• The Affiliated Hospital of Inner Mongolia Medical University — Hohhot, Inner Mongolia, China (Not_yet_recruiting)
• Xuzhou Center Hospital — Xuzhou, Jiangsu, China (Recruiting)
• First Hospital of Jilin University — Changchun, Jilin, China (Recruiting)
• JILIN Cancer Hospital — Changchun, Jilin, China (Not_yet_recruiting)
• Yunnan Cancer Hospital — Yunnan, Kunming, China (Not_yet_recruiting)
• Liaoning Province Cancer Hospital — Shenyang, Liaoning, China (Recruiting)
• The First Hospital of China Medical University — Shenyang, Liaoning, China (Not_yet_recruiting)
• Shanghai Chest Hospital — Shanghai, Shanghai Municipality, China (Not_yet_recruiting)
• Chongqing University Cancer Hospital — Chongqing, Sichuan, China (Recruiting)
• The Second Affiliated Hospital Zhejiang University School of Medicine — Hanzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Yuan LU

Conditions Solid Tumor