A Phase I Clinical Study of HLX3902 in Patients With mCRPC and Other Advanced Tumours

Official title

A Phase Ia Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of HLX3902 (a STEAP1xCD3xCD28 Trispecific Antibody) in Patients With Metastatic Castration-Resistant Prostate Cancer and Other Advanced Solid Tumours

Overview

This study is an open-label first-in-human phase I clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of HLX3902 in patients with mCRPC and other advanced solid tumours.

Interventions

• Drug HLX3902
  HLX3902 will be administered as an intravenous (IV) infusion.

Primary outcome measures

• Dose-Limiting Toxicity (DLT) [Time frame: At the end of Cycle 1 (each cycle is 4 weeks)]
• maximum tolerated dose (MTD) [Time frame: Up to approximately 2 years]

Secondary outcome measures (11)

• Number of participants with adverse events (AEs) [Time frame: Up to approximately 2 years]
• Number of participants with serious adverse events (SAEs) [Time frame: Up to approximately 2 years]
• Objective response rate (ORR) [Time frame: Up to approximately 2 years]
• disease control rate (DCR) [Time frame: Up to approximately 2 years]
• Duration of response (DOR) [Time frame: Up to approximately 2 years]
• Progression-free survival (PFS) [Time frame: Up to approximately 2 years]
• Overall survival (OS) [Time frame: Up to approximately 2 years]
• Prostate-specific antigen (PSA) response [Time frame: Up to approximately 2 years]
• PK parameters of HLX3902 [Time frame: Up to approximately 2 years]
• Incidence of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) against HLX3902 [Time frame: Up to approximately 2 years]
• PD biomarkers, including peripheral blood cytokines (e.g., IL-2, IL-6, TNF-α, and IFN-γ) and peripheral T-cell activation and proliferation. [Time frame: Up to approximately 2 years]

Eligibility criteria

Inclusion criteria

• Voluntarily signed written informed consent and willing to comply with study procedures.
• Age: ≥ 18 years, regardless of gender.
• Histologically confirmed advanced or metastatic solid tumours (e.g., metastatic castration-resistant prostate cancer (mCRPC), non-small cell lung cancer, or gastric cancer) following failure of standard therapy.
• mCRPC specifics: 1）Progression or refractory status after ≥ 1 novel anti-androgen agent and failure of 1-2 taxane-based regimens.

2）Ongoing surgical or medical castration (gonadotropin-releasing hormone agonist or antagonist) with serum testosterone ≤ 50 ng/dL.

3）Documented disease progression (prostate-specific antigen, nodal, visceral, or bone) .

5\. Presence of at least one measurable lesion per RECIST criteria version 1.1. 6. ECOG Performance Status of 0-1. 7. Expected survival exceeding 3 months. 8. Agreement to provide archived or fresh tumour tissue. 9. Adequate organ function. 10. Agreement to use effective contraception for both genders and negative pregnancy test for females of childbearing potential.

Exclusion criteria

• Presence of histological types other than adenocarcinoma in mCRPC; or neuroendocrine or small cell differentiation in other solid tumours.
• Active or symptomatic central nervous system metastases, carcinomatous meningitis, or spinal cord compression (stable treated brain metastases meeting protocol criteria are allowed).
• Active malignancies within two years prior to the first dose, except cured carcinoma in situ or basal cell carcinoma of the skin.
• Prior STEAP1-targeted therapy, or Radium-223/PSMA radionuclide therapy within 6 months.
• Major surgery, radiotherapy, chemotherapy, biological therapy, immunotherapy, or endocrine therapy (excluding LHRH/GnRH analogues) within 28 days; small molecule drugs within 14 days.
• Vaccination with live vaccines within 28 days.
• Systemic corticosteroids (> 10 mg/day Prednisone equivalent) or other immunosuppressants within 14 days.
• Currently participating in another interventional study or within 4 weeks of the end of treatment in such a study.
• Adverse events from prior therapy not resolved to Grade ≤ 1, except for alopecia, ear toxicity, or stable Grade ≤ 2 taxane-related neurotoxicity.
• History of Grade ≥ 2 immune-related pneumonitis or myocarditis, or severe/life-threatening immune-mediated adverse events during prior immunotherapy.
• Poorly controlled cardiovascular disease within 6 months, unstable angina, stroke, thromboembolic events, or uncontrolled hypertension or arrhythmia.
• Evidence of interstitial lung disease, or active non-infectious pneumonitis.
• Active or suspected autoimmune disease, hypophysitis, or unstable pituitary dysfunction requiring systemic therapy.
• Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks, active tuberculosis, or positive for HIV, active HBV (HBV DNA ≥ 500 IU/mL), or HCV.
• History of organ transplantation, central nervous system diseases within 12 months (e.g., seizures, dementia), or any condition that makes the participant unsuitable per Investigator.

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

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07533708 · HLX3902-FIH101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗