Advanced Solid Tumors
Conditions
Brief summary
This is a Phase Ia/Ib, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, and preliminary efficacy of HW221043 tablets in participants with advanced solid tumors. It includes two parts: the dose escalation study (Phase Ia) and the dose expansion study (Phase Ib).
Interventions
DRUGHW221043 Tablets
HW221043 Tablets for oral administration at specified doses on scheduled days.
Sponsors
Hubei Bio-Pharmaceutical Industrial Technological Institute Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women ≥18 years old. * Histologically and/or cytologically confirmed recurrent or metastatic advanced solid tumors. * Absence of available standard therapy, failure of standard therapy, or ineligibility for standard therapy. * Survival expectation is ≥12 weeks. * Adequate major organ function at screening; no blood transfusion or hematopoietic growth factor administration within 14 days prior to screening; and no significant abnormalities in hematology, coagulation profiles, or blood chemistry. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. * Presence of at least one measurable target lesion as defined by RECIST 1.1 * Participants are willing to provide tumor tissue samples. * Participants of childbearing potential must be non-pregnant at screening. Male and female of childbearing potential must agree to use effective methods of contraception throughout the study. * Participants must have demonstrated a full understanding of the study, voluntarily signed the informed consent form (ICF), and be willing and able to comply with all study procedures and required follow-up visits.
Exclusion criteria
* Allergic to HW221043 Tablet or its components. * Has a treatment history of KIF18A inhibitor. * Known presence of a recognizable hypermutated phenotype. * Prior receipt of any unapproved investigational drug or therapy within 28 days before first dose. * Inadequate washout from prior antitumor therapy. * Use of any medication that may interfere with the safety conduct of the study within 14 days prior to the first dose (or within at least 5 half-lives of the agent, whichever is longer), or planned use of such medications during the study period. * Continuous use of systemic corticosteroids within 4 weeks prior to the first dose. * Live vaccination within 28 days prior to first dose or anticipated during the study. * Major surgery within 28 days prior to the first dose of the investigational product. * Major surgical procedure within 28 days prior to first dose. * History of another active malignancy within 3 years prior to initiation of the investigational product. * ≥ Grade 2 prior antitumor therapy-related toxicity per CTCAE v6.0 (except abnormalities deemed clinically insignificant). * Tumor invasion into adjacent vital organs, major vessels, or central nervous system (CNS), or evidence of progressive brain metastases. * Presence of severe underlying pulmonary disease, severe cardiac/cerebrovascular disease, or clinically significant QTc prolongation. * Presence of an active infectious disease. * Diagnosis of an autoimmune disease or presence of an immunodeficient state. * Inability to swallow oral medications, or uncontrolled nausea, vomiting, diarrhea, or other gastrointestinal dysfunction likely to affect drug absorption. * History of alcohol abuse or substance abuse. * Women who are pregnant, breastfeeding, or planning to become pregnant/ breastfeeding during the study. * Any condition that, in the judgment of the Investigator, would make the participant unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AE) or Serious Adverse Events (SAE) | 2 years | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) according to NCI CTCAE 6.0. |
| Dose Limited Toxicity (DLT) | 2 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | 2 years | Highest Plasma Concentration of HW221043 |
| Area Under the Concentration-Time Curve (AUC) | 2 years | — |
| Tmax | 2 years | Time to Achieve Cmax |
| Objective Response Rate (ORR) | 2 years to 3 years | — |
| Progression-Free Survival (PFS) | 2 years to 3 years | — |
Countries
China
Contacts
CONTACTLifei Liu
Outcome results
None listed