Clinical trial NCT06304974: A Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
Official title: A Phase Ill Randomized Controlled Clinical Study Comparing BL-B01D1 With Chemotherapy of Physician's Choice as Second Line Treatment in Patients With Recurrent or Metastatic Esophageal Squamous Cell Carcinoma After Failure of PD-1/PD-L1 Monoclonal Antibody in Combination With Platinum-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2024-03-12
Enrollment: 488
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a registered phase Ill, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in patients with recurrent or metastatic esophageal squamous cell carcinoma after failure of PD-1/PD-L1 monoclonal antibody in combination with platinum-based chemotherapy.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol;
2. Age ≥18 years old;
3. Expected survival time ≥3 months;
4. Patients with recurrent or metastatic esophageal squamous cell carcinoma confirmed by histology or cytology;
5. Consent to provide archival tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years;
6. Must have at least one measurable lesion according to RECIST v1.1 definition;
7. ECOG 0 or 1;
8. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
9. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
10. No blood transfusion and no use of any cell growth factor drugs were allowed within 14 days before randomization, and the level of organ function had to be adequate;
11. Urine protein ≤2+ or \< 1000mg/24h;
12. A serum pregnancy test must be performed within 7 days before the start of treatment for premenopausal women who are likely to have children, and the result must be negative and must not be lactating; All enrolled patients should take adequate barrier contraception during the entire treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Chemotherapy, targeted therapy, biological therapy, etc., had been used within 4 weeks or 5 half-lives before randomization, and palliative radiotherapy and modern traditional Chinese medicine preparations approved by NMPA had been used within 2 weeks;
2. Patients with recurrent esophageal squamous cell carcinoma suitable for radical local treatment should be excluded;
3. Frontline received ADCs with topoisomerase I inhibitors as toxins;
4. History of severe heart disease and cerebrovascular disease;
5. Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
6. diagnosed with active malignancy within 3 years before randomization;
7. Hypertension poorly controlled by two antihypertensive drugs;
8. patients with poor glycemic control;
9. present with grade ≥1 radiation pneumonitis according to the RTOG/EORTC definition; A previous history of interstitial lung disease (ILD) or a suspicion of such disease on imaging during screening;
10. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
11. patients with active central nervous system metastases;
12. Severe infections within 4 weeks before randomization; Evidence of pulmonary infection or active pulmonary inflammation within 2 weeks before randomization;
13. patients with massive or symptomatic effusions or poorly controlled effusions;
14. Imaging examination showed that the tumor had invaded or wrapped around the large blood vessels in the abdomen, chest, neck, and pharynx;
15. serious unhealed wounds, ulcers, or fractures, or clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
16. patients with inflammatory bowel disease, extensive bowel resection history, immune enteritis history, intestinal obstruction or chronic diarrhea;
17. patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of BL-B01D1;
18. had a history of autologous or allogeneic stem cell transplantation;
19. Human immunodeficiency virus antibody positive, active hepatitis B virus infection or hepatitis C virus infection;
20. a history of severe neurological or psychiatric illness;
21. received other unmarketed investigational drugs or treatments within 4 weeks before randomization;
22. subjects scheduled for vaccination or who received live vaccine within 28 days before study randomization;
23. Other circumstances in which the investigator considered it inappropriate to participate in the trial because of complications or other circumstances.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 24 months
measure: Overall survival (OS)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Treatment Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to approximately 24 months
measure: T1/2
timeFrame: Up to approximately 24 months
measure: Anti-drug antibody (ADA)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Lin Shen, PHD
role: PRINCIPAL_INVESTIGATOR
References: