A Study to Compare the Efficacy and Safety of LY01015 and Opdivo® Combined Respectively With Chemotherapy in Advanced or Metastatic Esophageal Squamous Cell Carcinoma

Esophageal Squamous Cell Carcinoma Clinical Trial

Official title:

A Randomized, Double-blind, Multicenter, Phase 3 Study to Compare the Efficacy and Safety of LY01015 and Opdivo®（Nivolumab Injection）Combined Respectively With Fluorouracil Plus Cisplatin in Participants With Advanced or Metastatic Esophageal Squamous Cell Carcinoma.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06022861
• Other study ID #: LY01015/CT-CHN-302
• Status: Recruiting
• Phase: Phase 3
• Start date: October 12, 2023
• Est. completion date: December 2026

Study information

• Verified date: August 2023
• Source: Shandong Boan Biotechnology Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, double-blind, multicenter, Phase 3 study to compare the efficacy and safety of LY01015 and Opdivo®（Nivolumab Injection）combined respectively with fluorouracil plus cisplatin in participants with unresectable advanced, recurrent or metastatic previously untreated esophageal squamous cell carcinoma.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 510
• Est. completion date: December 2026
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Willing to sign the informed consent form.

2. Male or female aged 18 to 75 years patients.

3. Histopathologically confirmed esophagus squamous cell carcinoma.

4. Diagnosed with advanced or metastatic ESCC per AJCC 8th edition, not be amenable to curative approaches( such as definitive chemoradiation/surgery), not received prior systemic anti-cancer therapy for progressive or metastatic disease. Prior neoadjuvant, adjuvant or definitive radiotherapy/chemoradiotherapy/chemotherapy for locally advanced diseases is permitted if time from the last dose to recurrence> 24 weeks.

5. Must have at least one measurable lesion assessed by investigator per RECIST 1.1 criteria .

6. ECOG performance status of 0 to 1.

7. Prior to the first dose, the tumor tissue samples must be provided for PD-L1 expression analysis, and PD-L1 TPS=1%.

8. Expected survival =6 months.

9. Adequate organ function at screening.

Exclusion Criteria:

1. Presence of symptomatic brain metastasis or spinal compression, or history of meningeal metastasis. Patients with asymptomatic brain metastases who have received prior treatment are permitted to enroll if the disease is stable, and corticosteroids have not been required for at least 4 weeks prior to screening. Patients with carcinomatous meningitis are ineligible, regardless of whether the disease is clinically stable or not.

2. With high risks of bleeding or fistula due to apparent tumor invasion to esophagus or adjacent organs.

3. Known endoscopy-confirmed near-complete obstruction requiring interventional therapy or with risk of perforation post stent implantation in the esophagus or trachea.

4. Unstable disease within 6 months prior to signing informed consent form, including but not limited to unstable angina, myocardial infarction, NYHA Class II or higher cardiac failure, severe arrhythmia or cerebrovascular accident (including transient ischemic attacks) requiring treatment, or any other poorly-controlled systemic disease, for example, uncontrolled hypertension (systolic pressure =160 mmHg or diastolic pressure=100 mmHg) despite standard treatment.

5. Received prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 or anti-CTLA-4 agent or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

6. Prior cumulative exposure dose of cisplatin>300 mg/m2 and time from the last dose of cisplatin to randomization =12 month.

7. Received a live vaccine within 4 weeks prior to the first dose, or be scheduled to receive a live vaccine during the entire course of the study.

8. Received systemic chemotherapy, targeted therapy, immunosuppressants, immunostimulants, biological agents, Chinese herbal medicines for anti-tumor indications (prescription or medical record required), Chinese patent drug or any other investigational agents or participated in interventional clinical study within 4 weeks (or five half-lives, whichever is longer) prior to the first dose.

9. Other conditions, as determined by the investigator, for example, severe deep vein thrombosis, arterial embolism, hepatic encephalopathy, Child-Pugh grade B or more severe cirrhosis, or other acute or chronic disease, mental illnesses or laboratory abnormalities, which may lead to the following consequences: increase the risks associated with study participation or study drug administration, or interfere with the interpretation of study results.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma

Intervention

Drug:
• LY01015
Intravenouslly (IV) 240mg every 2 weeks (Q2W) during the combined chemotherapy period, thereafter, 480mg every 4 weeks(Q4W) during the maintenance treatment period
• Fluorouracil
Intravenouslly (IV) l 800mg/m2 every 4 weeks ((on Day 1 through Day 5)during the combined chemotherapy period
• Cisplatin
Intravenouslly (IV) 80mg/m2 every 4 weeks (Q4W) during the combined chemotherapy period
• Opdivo®
Intravenouslly (IV) 240mg every 2 weeks (Q2W) during the combined chemotherapy period, 480mg every 4 weeks(Q4W) during the maintenance treatment period within 24 weeks, thereafter converted to LY01015 480mg every 4 weeks(Q4W).

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou

Sponsors (1)

Lead Sponsor	Collaborator
Shandong Boan Biotechnology Co., Ltd

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate(ORR) as assessed by IRC		from baseline to week 16
Secondary	Objective Response Rate(ORR) as assessed by IRC and investigator		from baseline to week 24
Secondary	Disease Control Rate (DCR)		up to 2 years
Secondary	Duration of Response (DOR)		up to 2 years
Secondary	Progression-Free Survival (PFS)		up to 2 years
Secondary	16-week Progression-Free Survival Rate		from baseline to week 16
Secondary	24-week Progression-Free Survival Rate		from baseline to week 16
Secondary	Overall Survival (OS)		up to 2 years
Secondary	Incidence and severity of adverse effects (AEs)		up to 2 years
Secondary	Incidence of Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (Nab)		up to 2 years