Esophageal and/or Cardia Cancer, Melanoma, Urothelial Carcinoma (UC)
Conditions
Brief summary
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
DRUGHLX18
Participants will receive HLX18 (480 mg) on Day 1 of each 4-week cycle
DRUGOPDIVO®
Participants will receive OPDIVO® (480 mg) on Day 1 of each 4-week cycle
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| 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 |
Contacts
CONTACTChang Chen
Outcome results
None listed