A Study of HLX18 vs. OPDIVO® in Multiple Resected Solid Tumors

Official title

A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase I Clinical Study to Evaluate the Pharmacokinetic Profile, Efficacy, Safety and Immunogenicity of HLX18 vs. OPDIVO® (US-sourced OPDIVO®) in Multiple Resected Solid Tumors

Overview

This is a multicenter, randomized, double-blind, parallel-controlled phase I clinical study to evaluate the similarity in PK profile, efficacy, safety and immunogenicity of HLX18 and OPDIVO® in patients with resected esophageal or gastroesophageal junction cancer (EC/GEJC), melanoma (MEL), or urothelial carcinoma (UC).

Interventions

• Drug HLX18
  Participants will receive HLX18 (480 mg) on Day 1 of each 4-week cycle
• Drug OPDIVO®
  Participants will receive OPDIVO® (480 mg) on Day 1 of each 4-week cycle

Primary outcome measures

• AUC0-28d [Time frame: From time 0 to 28 days after the 1st dose(4 weeks)]
• AUCss [Time frame: From time 0 to 28 days after the 4th dose(16 weeks)]

Secondary outcome measures (8)

• maximum serum drug concentration (Cmax) [Time frame: up to 16 weeks]
• trough serum drug concentration (Ctrough) [Time frame: up to 16 weeks]
• maximum serum drug concentration at steady state (Cmax,ss) [Time frame: up to 16 weeks]
• trough serum drug concentration at steady state (Ctrough,ss) [Time frame: up to 16 weeks]
• Disease-free survival (DFS) [Time frame: up to 12 months]
• Adverse events (AEs); Serious adverse events (SAEs); Adverse events of special interest (AESIs) (including immune-related adverse events and infusion-related reactions) [Time frame: From enrollment to the end of 90-day safety follow-up (up to 15 months)]
• Number of participants with abnormal vital signs, abnormal physical examination findings, abnormal Laboratory tests results (hematology, serum chemistry, thyroid function, coagulation function, and myocardial markers) or abnormal 12-lead ECG readings. [Time frame: From enrollment to the end of 30-day safety follow-up (up to 13 months)]
• Incidence of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) [Time frame: up to 24 weeks]

Eligibility criteria

Inclusion criteria

• Participants must have signed and dated an IRB/IEC approved written informed consent form.
• Aged 18 to 70 years at the time of signing the ICF.
• 18 kg/m² ≤ BMI ≤ 30 kg/m² and 50 kg ≤ body weight ≤ 85 kg.
• Histologically confirmed solid tumors (EC/GEJC, Melanoma, or UC) status post R0 resection.
• For EC/GEJC: residual pathologic disease (non-pCR) following neoadjuvant chemoradiotherapy and R0 resection.
• For Melanoma: Stage IIB-IV after complete surgical resection with documented negative margins.
• For UC: High-risk muscle-invasive urothelial carcinoma (MIUC) following radical resection (R0).
• Documented disease-free status (no recurrence) by imaging and physical exam within 4 weeks prior to randomization.
• Adequate recovery from prior surgery or systemic therapy.
• ECOG Performance Status of 0.
• Adequate organ function.
• Agreement to use effective contraception (negative pregnancy test for WOCBP).

Exclusion criteria

• History of illicit drug use or alcohol abuse within 12 months prior to randomization.
• Tumor-specific exclusions: cervical esophageal cancer, Stage IV EC/GEJC, or ocular melanoma.
• UC-specific surgical exclusions: status post partial cystectomy or partial nephrectomy.
• EC/GEJC treatment violations: failure to receive mandatory preoperative concurrent CRT (mono-therapy is ineligible).
• Prior treatment with nivolumab or any other immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4).
• Other primary active malignancies within 5 years or history of organ/bone marrow transplantation.
• Significant cardiovascular disease (MI, cerebrovascular disease) or unstable arrhythmia (QTc > 450ms/470ms) within 6 months.
• Chronic heart failure (NYHA Class III-IV) or LVEF < 50% at screening.
• Presence of interstitial pneumonia, pneumonitis, or severe lung function abnormalities.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Known HIV infection, active Hepatitis B/C, or active pulmonary tuberculosis.
• Peripheral neuropathy ≥ Grade 2 or history of carcinomatosis meningitis.
• Use of systemic corticosteroids (>10 mg/day prednisone equivalent), immunosuppressants, or live vaccines within 28 days.
• Recent or planned participation in other investigational drug, device, or surgical studies.
• Severe allergic reactions to monoclonal antibodies or any condition deemed unsuitable by the investigator.
• The investigator has a clear reason to believe that participation in this study would be detrimental to the participant.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 7 centers

• Fujian Medical University Union Hospital — Fuzhou
• The First Affiliated Hospital Zhejiang University School Of Medicine — Hangzhou
• The First Affiliated Hospital of Henan University of Science & Technology — Luoyang
• The Second Hospital of Tianjin Medical University — Tianjin
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou
• Union Hospital, Tongji Medical College,Huazhong University of Science and Technology — Wuhan
• The Second Affiliated Hospital of Xi'an Jiaotong University — Xi'an

Identifiers

NCT: NCT07518043 · HLX18-MRST001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗