A Study of BL-B01D1 Combined With Osimertinib Mesylate Tablets in Patients With Non-small Cell Lung Cancer

A Phase II Clinical Study to Evaluate the Efficacy and Safety of BL-B01D1 for Injection in Combination With Osimertinib Mesylate Tablets in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer With EGFR-sensitive Mutations

A Phase II clinical study to evaluate the efficacy and safety of BL-B01D1 for injection in combination with Osimertinib Mesylate Tablets in patients with locally advanced or metastatic non-small cell lung cancer with EGFR-sensitive mutations

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: BL-B01D1; Drug: Osimertinib Mesylate Tablets

Detailed Description

Objective: To evaluate the safety, tolerability, and efficacy of BL-B01D1 in combination with Osimertinib Mesylate Tablets in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations, and to further explore the optimal dose and mode of combination. Secondary objective: To evaluate the PK, immunogenicity, and drug-drug interaction (DDI) of the investigational drug BL-B01D1. Exploratory objective: To explore potential predictive, prognostic biomarkers in relation to study drug therapy responses, including levels of biomarkers, including but not limited to EGFR, HER3, etc., in archived and/or fresh tumor tissue and blood samples obtained before and/or after study therapy completion, and/or at the time of disease progression.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Pulmonary Hospital
      • Contact: Tao Gui; Phone Number: 021-65115006-1019; Email: fkyygcp@163.com
      • Principal Investigator: Caicun Zhou, PHD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Sign the informed consent voluntarily and follow the program requirements;
2. No gender limitation;
3. Age ≥18 years old;
4. Expected survival time ≥3 months;
5. Initially treated locally advanced or metastatic non-small cell lung cancer patients with EGFR 19DEL or L858R mutation confirmed by histopathology and/or cytology;
6. Agrees to provide archived tumor tissue samples or fresh tissue samples of primary lesion or metastasis within 6 months for biomarker detection; If a subject is unable to provide a tumor tissue sample, he/she may be enrolled after evaluation by the investigator if other inclusion criteria are met.
7. There must be at least one measurable lesion consistent with the RECIST v1.1 definition;
8. Physical condition score ECOG ≤1 score;
9. The toxicity of previous antitumor therapy has returned to ≤ level 1 as defined by NCI-CTCAE v5.0. (The investigators considered asymptomatic laboratory abnormalities such as elevated ALP, hyperuricemia, serum amylase/lipase, and elevated blood glucose, and judged toxicity without safety risk. Such as hair loss, grade 2 peripheral neurotoxicity, stable hypothyroidism on hormone replacement therapy, and decreased hemoglobin but ≥90 g/L, etc.);
10. No serious 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 ≥100×109/L, hemoglobin ≥90 g/L;
    2. Liver function: total bilirubin TBIL≤1.5×ULN (total bilirubin ≤3×ULN in subjects with Gilbert's syndrome or liver metastasis), AST and ALT ≤2.5×ULN in subjects without liver metastasis, AST and ALT ≤5.0×ULN in subjects with liver metastasis;
    3. Kidney function: creatinine (Cr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula).
12. Coagulation function: International standardized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5×ULN;
13. Urine protein ≤2+ or ≤1000mg/24h;
14. Fertile female subjects or male subjects whose partners are fertile must use highly effective contraception from 7 days before the first dose until 6 months after the first dose. A fertile female subject must have a negative serum pregnancy test within 7 days prior to initial dosing.

Exclusion Criteria:

1. Patients who have previously received systemic therapy (except for disease progression more than 6 months after the last administration of neoadjuvant therapy or adjuvant therapy);
2. Previous treatment with EGFR-TKI;
3. Participants who participated in any other clinical trial within 4 weeks prior to this trial administration (based on the time of last administration);

4. Received chemotherapy, radiotherapy (small area radiotherapy for bone pain patients with bone metastases within 2 weeks before the first use of study drugs), biological therapy, immunotherapy and other antitumor treatments within 4 weeks before the first use of study drugs, except the following:

   1. Oral administration of fluorouracil and small-molecule targeted drugs within 2 weeks prior to first use of the study drug or within 5 half-lives of the drug, whichever is longer;
   2. Traditional Chinese medicines with anti-tumor indications should be used within 2 weeks before the first use of study drugs;
5. Had major surgery (as defined by the investigator) within 4 weeks prior to initial administration;
6. Present with, or history of, interstitial lung disease, drug-induced interstitial pneumonia, radiation pneumonia requiring steroid treatment;
7. Systemic serious infections, including but not limited to severe pneumonia caused by fungi, bacteria or viruses, bacteremia or serious infectious complications, occurred within 4 weeks before screening;
8. Patients at risk of active autoimmune disease, or with a history of autoimmune disease, Including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener syndrome, autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, autoimmune neuropathy (Guillain-Barre syndrome), etc. Exceptions include type I diabetes, hypothyroidism stable with hormone replacement therapy (including hypothyroidism caused by autoimmune thyroid disease), psoriasis or vitiligo that do not require systemic therapy;
9. Patients with other malignant tumors within 5 years prior to the first administration, except for cured squamous cell carcinoma of the skin, basal cell carcinoma, superficial bladder carcinoma, and carcinoma in situ of the prostate/cervix/breast, etc., which could be included in the study;
10. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBsAg positive or HBcAb positive, and HBV-DNA copy number > lower limit of central detection) or hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower limit of central detection);
11. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);

12. A history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

    1. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, degree III atrioventricular block, complete left bundle branch block, frequent and uncontrollable arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation, and ventricular flutter (except transient);
    2. Prolonged QT interval at rest (QTc > 450 msec in men or 470 msec in women);
    3. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurring within 6 months prior to initial administration;
    4. Heart failure ≥II on the New York Heart Association (NYHA) cardiac function scale;
13. Patients with a large number of serous effusion, or patients with serous effusion and obvious symptoms, or patients with poorly controlled serous effusion (poorly controlled is defined as two or more times of puncture and drainage in a month);
14. Patients with central nervous system (CNS) metastasis and/or cancerous meningitis (meningeal metastasis). But have received brain metastases (radiation or surgery; Patients with stable BMS who had stopped radiotherapy or surgery 28 days before the first dose were enrolled, and patients with cancerous meningitis (meningeal metastasis) were excluded even after treatment and judged stable. Stable was defined as asymptomatic, stable, and not requiring steroid treatment for at least 4 weeks prior to study treatment.
15. Previous history of allogeneic stem cell, bone marrow or organ transplantation;
16. Patients with a history of allergy to recombinant humanized antibody or to any excipient component of BL-B01D1;
17. History of autologous or allogeneic stem cell transplantation;
18. Pregnant or nursing women;
19. The other conditions of participation in this clinical trial were not considered appropriate by the investigators.

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 receive BL-B01D1 in combination with Osimertinib Mesylate Tablets in the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: BL-B01D1; Administration by intravenous infusion; Drug: Osimertinib Mesylate Tablets; Osimertinib Mesylate Tablets will be administered at a fixed dose of 80mg daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 BL-B01D1.	Up to approximately 24 months
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The PFS is defined as the time from the participant's first dose of BL-B01D1 to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months
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
Treatment-Emergent Adverse Event (TEAE)	TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-B01D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-B01D1.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Caicun Zhou, PhD, Shanghai Pulmonary Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: May 25, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Estimated): August 31, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Locally advanced or metastatic non-small cell lung cancer; EGFR sensitive mutation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Osimertinib
• Other Study ID Numbers: BL-B01D1-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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