A Study of BL-B01D1 in Combination With Osimertinib Versus Osimertinib as First-Line Treatment in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer(PANKU-Lung04)

A Phase III Randomized Study of BL-B01D1 in Combination With Osimertinib Versus Osimertinib as First-Line Treatment in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This trial is a registered phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in combination with osimertinib versus osimertinib as first-Line treatment in patients with EGFR-mutated locally advanced or metastatic Non-small Cell Lung Cancer.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 720
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: 15013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Shanghai East Hospital
      • Contact: Caicun Zhou

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Sign the informed consent form voluntarily and follow the protocol requirements;
2. Age ≥18 years old;
3. Expected survival time ≥3 months;
4. Patients with unresectable or radical radiotherapy for locally advanced non-small cell lung cancer;
5. Documentation of EGFR sensitive mutations detected from tumor tissue or blood samples;
6. Consent to provide archived tumor tissue samples or fresh tissue samples of primary or metastatic lesions at or after diagnosis for testing, including EGFR mutation type;
7. At least one measurable lesion meeting the RECIST v1.1 definition was required;
8. ECOG 0 or 1;
9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. The organ function level must meet the requirements on the premise that blood transfusion and colony-stimulating factor are not allowed within 14 days before the screening period;
12. Urinary protein ≤2+ or < 1000mg/24h;
13. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and the patient must not be 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. Previous histologic or cytological evidence of small cell or mixed small/non-small cell components;
2. Patients with previous systemic therapy;
3. Patients had received EGFR-TKI therapy;
4. Studies received radical radiotherapy, major surgery, and large area radiotherapy within 4 weeks before randomization;
5. History of severe heart disease and cerebrovascular disease;
6. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
7. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
8. Were diagnosed with active malignancy within 3 years before randomization;
9. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg);
10. Patients with poor glycemic control;
11. A history of ILD requiring steroid therapy, or current ILD or grade ≥2 radiation pneumonitis, or a suspicion of such disease;
12. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
13. Patients with active central nervous system metastasis;
14. Had a severe infection within 4 weeks before randomization;
15. Patients with massive or symptomatic effusions or poorly controlled effusions;
16. Imaging examination showed that the tumor had invaded or enveloped the large blood vessels in the abdomen, chest, neck, and pharynx;
17. Serious unhealed wound, ulcer, or fracture within 4 weeks before signing the informed consent;
18. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
19. Patients with a history of inflammatory bowel disease, extensive bowel resection, immune enteritis, intestinal obstruction or chronic diarrhea;
20. Patients with a history of allergy to recombinant humanized antibodies or to any of the excipients of BL-B01D1;
21. Had autologous or allogeneic stem cell transplantation history;
22. Human immunodeficiency virus antibody positive, active hepatitis B virus infection or hepatitis C virus infection;
23. A history of severe neurological or psychiatric illness;
24. Received other unmarketed investigational drugs or treatments within 4 weeks before randomization;
25. Subjects scheduled for vaccination or who received live vaccine within 28 days before study randomization;
26. Other circumstances in which the investigator considered it inappropriate to participate in the trial because of complications or other circumstances.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BL-B01D1 in Combination with Osimertinib; Participants receive BL-B01D1 in Combination with Osimertinib for 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 for a cycle of 3 weeks.; Other Names: BMS-986507; iza-bren; izalontamab brengitecan; Drug: Osimertinib; Oral administration, 80mg daily for a cycle of 3 weeks.
Active Comparator: Osimertinib; Participants receive Osimertinib for 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: Osimertinib; Oral administration, 80mg daily for a cycle of 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) as assessed by BIRC is defined as the time between the date subjects are randomized and the first observation of disease progression (based on BICR's image-based assessment) or death.	Up to approximately 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Overall survival (OS) is defined as the time between the subject's randomization date and subject's death.	Up to approximately 36 months
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the number of CR and PR in the treatment and control groups divided by the number of that group in the full analysis set (FAS).	Up to approximately 36 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) : Percentage of all randomized subjects who rated the best overall response (BOR) as complete response (CR), partial response (PR), and disease stabilization (SD) according to RECIST 1.1 criteria.	Up to approximately 36 months
Duration of Response (DOR)	Duration of Response (DOR) : defined as the period from the date when tumor response is first recorded to the date when objective tumor progression is first recorded or the date of death.	Up to approximately 36 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 36 months
Anti-drug antibody (ADA)	Frequency of anti-BL-B01D1 antibody (ADA) will be investigated.	Up to approximately 36 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: February 16, 2025
• First Submitted That Met QC Criteria: February 16, 2025
• First Posted (Actual): February 20, 2025

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; osimertinib
• Other Study ID Numbers: BL-B01D1-308

Drug and device information, study documents

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