HWS116 Monotherapy in Patients With Advanced Solid Tumors

Official title

A Phase I, Single-Arm, Open-Label, Dose-Escalation and Expansion Study of HWS116 Injection in Advanced Solid Tumors

Overview

This is a Phase I open-label study that will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of HWS116 monotherapy in patients with advanced solid tumors.

Detailed description

This trial is an open-label, dose-escalation/expansion first-in-human study of HWS116, divided into two parts:

Part 1 (Dose Escalation): This part plans to enroll patients with advanced solid tumors who have no standard treatment, have failed standard treatment, or are ineligible for standard treatment. Patients will receive monotherapy with HWS116 at pre-specified escalating doses. The objectives are to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of HWS116 in patients.

Part 2 (Dose Expansion): This part intends to enroll patients with advanced solid tumors who have no standard treatment, have failed standard treatment, or are ineligible for standard treatment. Patients will receive continuous administration of HWS116 to provide additional clinical data for evaluating preliminary efficacy and determining the Phase 2 recommended dose (P2RD) and potential indications.

Interventions

• Drug HWS116 Injection
  Administered intravenous infusion at pre-specified doses every two weeks.

Primary outcome measures

• Incidence of Treatment-Emergent Adverse Events (Part 1 Only) [Time frame: Up to 2 years]
• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Part 2 Only) [Time frame: Up to 2 years]

Secondary outcome measures (12)

• Pharmacokinetic Parameter: Maximum Plasma Concentration (Cmax) [Time frame: Up to 2 years]
• Pharmacokinetic Parameter: Area under the Concentration-Time Curve (AUC0-t) [Time frame: Up to 2 years]
• Pharmacokinetic Parameter: Area under the Concentration-Time Curve (AUC0-∞) [Time frame: Up to 2 years]
• Pharmacokinetic Parameter: Steady-State Peak Concentration (Cmax,ss) [Time frame: Up to 2 years]
• Pharmacokinetic Parameter: Steady-State trough Concentration (Cmin,ss) [Time frame: Up to 2 years]
• Pharmacokinetic Parameter: Steady-State Area under the Curve (AUCss) [Time frame: Up to 2 years]
• Number of Patients with Dose-limiting Toxicities (DLTs) during the DLT Assessment Period (Part 1 Only) [Time frame: Up to 2 years]
• Maximum Tolerated Dose (MTD) Based on Number of DLTs (Part 1 Only) [Time frame: Up to 2 years]
• Phase II Recommended Dose [Time frame: Up to 2 years]
• Preliminary Efficacy: Objective Response Rate (ORR) (Part 1 Only) [Time frame: Up to 2 years]
• Preliminary Efficacy: Progression-Free Survival (PFS) [Time frame: Up to 2 years]
• Preliminary Efficacy: Overall Survival (OS) [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

• Aged ≥18 years at the time of signing the Informed Consent Form (ICF);
• Patients with recurrent or metastatic solid tumors confirmed by histology or cytology, who have progressed or developed intolerance after System Organ Class (SOC), or have no SOC available, or are not suitable for SOC, including but not limited to colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer, and cholangiocarcinoma;
• According to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, there is at least one evaluable lesion or one measurable target lesion；
• Life expectancy ≥ 12 weeks;
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score is 0 or 1；
• Participant must have adequate main organ function.
• Participants who are capable of having children must agree to use two medically approved effective contraceptive methods during the study and for 6 months after the last dose. Women of childbearing age must have a negative serum pregnancy test within 7 days before dosing；
• Have a full understanding of this study, voluntarily sign the informed consent form, and be able to follow the study's operating procedures and requirements for follow - up examinations.

Exclusion criteria

• Known allergy to the investigational product, drugs of the same class, or any excipients;
• Have previously received any Fibroblast Growth Factor- Fibroblast Growth Factor Receptor (FGF-FGFR) pathway inhibitor;
• For previous anti-tumor therapies (including investigational products/treatments): those who have received chemotherapy, small molecule targeted therapy, endocrine therapy, herbal medicine therapy/physiotherapy within 14 days prior to the first dose or within at least 5 half-lives of the corresponding drug, whichever is longer; or those who have undergone surgery (excluding diagnostic procedures such as needle biopsy), radiotherapy (palliative radiation for non-target lesions is within 14 days prior to the first dose), biotherapy, immunotherapy, or other anti-tumor therapies within 28 days prior to the first dose or within at least 5 half-lives of the corresponding drug, whichever is longer;
• Have undergone major surgery within 28 days prior to the first dose;
• Have Grade ≥ 2 toxicity caused by previous anti-tumor treatment prior to the first dose, except for those deemed by investigators to pose no safety risk, such as alopecia, pigmentation, or specific laboratory abnormalities;
• Have corneal defects, or other known corneal abnormalities that may increase the risk of corneal ulcer . undergone corneal surgery within 6 months prior to the first dose;
• Have severe cardiovascular or cerebrovascular diseases；
• Have a history of clinically significant corrected QT Interval (QTc) prolongation, or QTc interval > 480 msec at screening;
• Metastases to central nervous system with clinical symptoms or active progression;
• Have tested positive for hepatitis B surface antigen (HBsAg) (except for patients with hepatocellular carcinoma) with hepatitis B virus deoxyribonucleic acid (HBV DNA) > 1000 IU/mL, or positive for hepatitis C virus (HCV) antibody with HCV ribonucleic acid (RNA) positive, or positive for human immunodeficiency virus (HIV) antibody, or have active syphilis;
• Have autoimmune diseases, immunodeficiencies, a history of organ transplantation, or are planning to undergo organ transplantation;
• Presence of any severe, uncontrolled clinical issues (e.g., uncontrolled malignant pleural effusion, ascites, pericardial effusion, or unstable psychiatric conditions) deemed unsuitable for study participation by the investigator；
• Have acute inflammation or clinically significant active infections;
• Have a history of alcohol abuse or drug abuse;
• Pregnant or lactating women or women who are preparing for pregnancy or lactation during the study period;
• Any other condition that, at the discretion of investigators, renders the participant unsuitable for enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University — Guangzhou

Identifiers

NCT: NCT07413328 · RFFG-2025-07

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗