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

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma; Esophageal and/or Cardia Cancer; Urothelial Carcinoma (UC)
• Intervention / Treatment: Drug: HLX18; Drug: OPDIVO®

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chang Chen; Phone Number: +86 138 1686 9003; Email: chenthoracic@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must have signed and dated an IRB/IEC approved written informed consent form.
2. Aged 18 to 70 years at the time of signing the ICF.
3. 18 kg/m² ≤ BMI ≤ 30 kg/m² and 50 kg ≤ body weight ≤ 85 kg.
4. Histologically confirmed solid tumors (EC/GEJC, Melanoma, or UC) status post R0 resection.
5. For EC/GEJC: residual pathologic disease (non-pCR) following neoadjuvant chemoradiotherapy and R0 resection.
6. For Melanoma: Stage IIB-IV after complete surgical resection with documented negative margins.
7. For UC: High-risk muscle-invasive urothelial carcinoma (MIUC) following radical resection (R0).
8. Documented disease-free status (no recurrence) by imaging and physical exam within 4 weeks prior to randomization.
9. Adequate recovery from prior surgery or systemic therapy.
10. ECOG Performance Status of 0.
11. Adequate organ function.
12. Agreement to use effective contraception (negative pregnancy test for WOCBP).

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX18; Participants will receive HLX18 (480 mg) on Day 1 of each 4-week cycle, until 12 months after the randomization (nearly 13 cycles) or investigator-assessed disease recurrence, death, initiation of new anti-tumor therapy, unacceptable drug toxicity, withdrawal of informed consent form, or study termination (whichever occurs first).	Drug: HLX18; Participants will receive HLX18 (480 mg) on Day 1 of each 4-week cycle
Active Comparator: OPDIVO®; Participants will receive OPDIVO® (480 mg) on Day 1 of each 4-week cycle, for a total of 4 cycles (16 weeks). After 4 cycles, all participants in the OPDIVO® group will receive HLX18 480 mg on Day 1 of each 4-week cycle until 12 months after the randomization (nearly 13 cycles) or investigator-assessed disease recurrence, death, initiation of new anti-tumor therapy, unacceptable drug toxicity, withdrawal of informed consent form, or study termination (whichever occurs first).	Drug: OPDIVO®; Participants will receive OPDIVO® (480 mg) on Day 1 of each 4-week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-28d	From time 0 to 28 days after the 1st dose(4 weeks)
AUCss	From time 0 to 28 days after the 4th dose(16 weeks)

Secondary Outcome Measures

Outcome Measure	Time Frame
maximum serum drug concentration (Cmax)	up to 16 weeks
trough serum drug concentration (Ctrough)	up to 16 weeks
maximum serum drug concentration at steady state (Cmax,ss)	up to 16 weeks
trough serum drug concentration at steady state (Ctrough,ss)	up to 16 weeks
Disease-free survival (DFS)	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)	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.	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)	up to 24 weeks

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2026
• Primary Completion (Estimated): August 12, 2027
• Study Completion (Estimated): June 13, 2028

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Carcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Carcinoma, Transitional Cell; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• Other Study ID Numbers: HLX18-MRST001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No