A Study of SI-B003 and BL-B01D1+SI-B003 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer, Nasopharyngeal Carcinoma and Other Solid Tumors

A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B003 Monotherapy and BL-B01D1+SI-B003 Combination Therapy in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer, Nasopharyngeal Carcinoma and Other Solid Tumors

Phase II: To explore the efficacy, safety and tolerability of BL-B01D1+SI-B003 in patients with locally advanced or metastatic non-small cell lung cancer and nasopharyngeal carcinoma, and to further explore the optimal dose and mode of combination.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: BL-B01D1; Drug: SI-B003

Detailed Description

Phase II: To explore the efficacy of BL-B01D1+SI-B003 combination in patients with locally advanced or metastatic solid tumors such as non-small cell lung cancer and nasopharyngeal carcinoma. To explore the safety and tolerability of BL-B01D1+SI-B003 combination in patients with locally advanced or metastatic non-small cell lung cancer and nasopharyngeal carcinoma, and to further explore the optimal dose and mode of combination.

• Study Type: Interventional
• Enrollment (Estimated): 121
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hai Zhu, PHD; Phone Number: +8613980051002; Email: zhuhai@baili-pharm.com
• Study Contact Backup: Name: Sa Xiao, PHD; Phone Number: +8615013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Not yet recruiting
      • Chongqing University Cancer Hospital
      • Contact: Xiaolei Shu
  • Fujian
    • Fuzhou, Fujian, China
      • Not yet recruiting
      • Fujian Cancer Hospital
      • Contact: Wu Zhuang
  • Guangdong
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
      • Contact: Xiaoming Huang
    • Guangzhou, Guangdong, China, 510000
      • Not yet recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: Li Zhang
    • Guangzhou, Guangdong, China
      • Not yet recruiting
      • The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Yong Chen
  • Guangxi
    • Liuzhou, Guangxi, China
      • Not yet recruiting
      • Liuzhou People's Hospital
      • Contact: Zhanxiong Luo
  • Henan
    • Luoyang, Henan, China
      • Not yet recruiting
      • The First Affiliated Hospital of Henan University of Science and Technology
      • Contact: Zhiye Zhang
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Cancer Hospital
      • Contact: Yanqiu Zhao
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Conghua Xie
      • Contact: Yahua Zhong
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Union Hospital Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Kunyu Yang
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Hunan Cancer Hospita
      • Contact: Yaqian Han
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Nanchang University
      • Contact: Fei Xu
  • Shangdong
    • Linyi, Shangdong, China
      • Recruiting
      • LinYi Cancer Hospital
      • Contact: Zhen Wang
  • Shanxi
    • Xi'an, Shanxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xi'an Jiao Tong University
      • Contact: Yi Yao
  • Tianjin
    • Tianjin, Tianjin, China
      • Not yet recruiting
      • Tianjin Medical University General Hospital
      • Contact: Diansheng Zhong
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • Zhejiang Cancer Hospital
      • Contact: Yun Fan

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol;
2. No gender limit;
3. Age: ≥18 years old and ≤75 years old;
4. expected survival time ≥3 months;

5. Patients with histologically and/or cytologically confirmed locally advanced or metastatic solid tumors such as non-small cell lung cancer and nasopharyngeal carcinoma:

   Stage I: patients with histologically and/or cytologically confirmed locally advanced or metastatic non-small cell lung cancer and nasopharyngeal carcinoma who failed standard treatment; Stage 2: patients with histologically and/or cytologically confirmed locally advanced or metastatic non-small cell lung cancer or nasopharyngeal carcinoma who failed standard treatment;

   Phase 3:

   Cohort_A: Patients with histologically and/or cytologically confirmed locally advanced or metastatic EGFRwt, ALKwt non-small cell lung cancer who failed standard therapy; Cohort_B: Patients with histologically and/or cytologically confirmed locally advanced or metastatic EGFRmut non-small cell lung cancer who had failed EGFR TKI therapy and had not received systemic chemotherapy; Note: a. Patients were eligible if they were treated directly with third-generation EGFR TKI, or if they were treated with first-generation or second-generation EGFR TKI before progression to third-generation TKI; b. If the patient has progressed after the first and second generation EGFR TKI treatment, and there is no indication for the third generation EGFR TKI treatment, the third generation EGFR TKI treatment is not required; Cohort_C: Patients with histologically and/or cytologically confirmed locally advanced or metastatic nasopharyngeal carcinoma who failed standard treatment;

6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 years; Participants who were unable to provide tumor tissue samples could be enrolled if they met other inclusion and exclusion criteria after evaluation by investigators.
7. Must have at least one measurable lesion according to RECIST v1.1 definition;
8. ECOG 0 or 1;
9. Toxicity of previous antineoplastic therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities considered by investigators, such as elevated alkaline phosphatase, hyperuricemia, and elevated blood glucose; Toxicities that were judged by the investigators to be no safety risk, such as alopecia and grade 2 peripheral neurotoxicity, were excluded. Or decreased hemoglobin (≥90 g/L);
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;

11. The level of organ function must meet the following requirements and meet the following standards:

    1. Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥90×109/L, hemoglobin ≥90 g/L;
    2. Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN in patients without liver metastasis, AST and ALT ≤5.0 ULN in patients with liver metastasis;
    3. Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula).
12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 ULN;
13. Urine protein ≤2+ or ≤1000mg/24h;
14. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the start of treatment, serum or urine must be negative for pregnancy, and must be non-lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. For phase 3 Cohort_A, patients with MET 14 exon skipping, ROS1 rearrangement, BRAF V600 mutation, NTRK fusion, or RET rearrangement on previous sequencing reports of tissue samples or ctDNA prior to signing of informed consent were excluded;
2. Antineoplastic therapy such as chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule tyrosine kinase inhibitors) within 4 weeks or 5 half-life times (whichever is shorter) before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral fluorouracil drugs such as S-1, capecitabine, or palliative radiotherapy within 2 weeks before the first dose;
3. Patients with a history of immunotherapy and grade ≥3 irAE or grade ≥2 immune-related myocarditis must be excluded;
4. The use of immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., within 14 days before the first use of the study drug must be excluded;
5. History of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥ grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ grade 2 heart failure, transmural myocardial infarction, unstable angina, etc.
6. Prolonged QT interval (QTc > 450 msec in men or QTc > 470 msec in women), complete left bundle branch block, and III degree atrioventricular block;
7. Systemic corticosteroids (> 10mg/ day of prednisone, or other corticosteroids equivalent) or immunosuppressive agents are required within 2 weeks before the study administration; Exceptions include inhaled or topical administration of steroids or physiological replacement doses of steroids for adrenal insufficiency;
8. Active autoimmune and inflammatory diseases (e.g., systemic lupus erythematosus, psoriasis requiring systemic therapy, rheumatoid arthritis, inflammatory bowel disease, and Hashimoto's thyroiditis; The exceptions are type I diabetes mellitus, hypothyroidism that can be controlled only by replacement therapy, and skin diseases (such as vitiligo and psoriasis) that do not require systemic treatment.
9. Other malignancies diagnosed within 5 years before the first dose, except for radical basal cell carcinoma, squamous cell carcinoma, and/or radical resection carcinoma in situ;
10. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
11. Pulmonary disease defined as grade ≥3 according to CTCAE v5.0; Patients with existing or a history of interstitial lung disease (ILD);
12. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring medical intervention within 6 months before screening; Infusion-related thrombosis was excluded.
13. Patients with massive or symptomatic effusions, or those who underwent drainage within 4 weeks before signing the informed consent;

14. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (meningeal metastases). Patients who had received treatment for brain metastases (radiotherapy or surgery; Patients with stable brain metastases who had stopped radiotherapy or surgery 28 days before the first dose were eligible. Patients with cancerous meningitis (meningeal metastasis) were excluded even if they were treated and judged to be stable. Stability is defined as meeting the following four criteria:

    1. seizure-free status for > 12 weeks with or without antiepileptic medication;
    2. no need for corticosteroids;
    3. the long diameter of brain metastases < 10mm;
    4. stable and asymptomatic for more than one month after treatment;
15. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any ingredient of BL-B01D1 or SI-B003;
16. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
17. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > 103 IU/ml) or hepatitis C virus infection (HCV antibody positive and HCV-RNA > detection limit);
18. Active infection requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
19. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of last dose);
20. Other conditions for participation in the trial were not considered appropriate by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study treatment; Participants received SI-B003 and BL-B01D1+SI-B003 in the first cycle (3 weeks). Participants who had a clinical benefit could receive additional cycles of additional treatment. Administration will be discontinued because of disease progression or intolerable toxicity or for other reasons.	Drug: BL-B01D1; Administration by intravenous infusion; Drug: SI-B003; Administration by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.	Up to approximately 24 months
Recommended Phase II Dose (RP2D)	The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of SI-B003.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]).	Up to approximately 24 months
Duration of response (DOR)	The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months
Progression-free survival (PFS)	The PFS is defined as the time from the first dose of medication to disease progression or death, whichever occurred first.	Up to approximately 24 months
Treatment-Emergent Adverse Event (TEAE)	TEAE is defined as any adverse and unexpected change in body structure, function, or chemistry or any exacerbation of an existing condition (i.e., any clinically significant adverse change in frequency and/or intensity) during treatment. The type, frequency, and severity of TEAE will be assessed during treatment.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Li Zhang, PHD, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2024
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: July 13, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 21, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 18, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
• Other Study ID Numbers: BL-B01D1-SI-B003-201-01

Drug and device information, study documents

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