Clinical trial NCT06022861: A Study to Compare the Efficacy and Safety of LY01015 and Opdivo® Combined Respectively With Chemotherapy in Advanced or Metastatic Esophageal Squamous Cell Carcinoma
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Lead sponsor: Shandong Boan Biotechnology Co., Ltd
Sponsor class: INDUSTRY
First posted: 2023-09-05
Enrollment: 510
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate(ORR) as assessed by IRC
timeFrame: from baseline to week 16
Secondary outcomes:
measure: Objective Response Rate(ORR) as assessed by IRC and investigator
timeFrame: from baseline to week 24
measure: Disease Control Rate (DCR)
timeFrame: up to 2 years
measure: Duration of Response (DOR)
timeFrame: up to 2 years
measure: Progression-Free Survival (PFS)
timeFrame: up to 2 years
measure: 16-week Progression-Free Survival Rate
timeFrame: from baseline to week 16
measure: 24-week Progression-Free Survival Rate
timeFrame: from baseline to week 16
measure: Overall Survival (OS)
timeFrame: up to 2 years
measure: Incidence and severity of adverse effects (AEs)
timeFrame: up to 2 years
measure: Incidence of Anti-Drug Antibodies (ADA) and Neutralizing Antibodies (Nab)
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
Study officials:
References: