A Study Comparing BL-B01D1 in Combination With Osimertinib Versus Osimertinib Alone in Patients With Locally Advanced, Unresectable EGFR-mutated Non-small Cell Lung Cancer(Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy(PANKU-Lung08)

Official title

A Phase III Randomized Controlled Clinical Study Comparing BL-B01D1 in Combination With Osimertinib Versus Osimertinib Alone in Patients With Locally Advanced, Unresectable EGFR-mutated Non-small Cell Lung Cancer(Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy(PANKU-Lung08)

Overview

This trial is a registrational Phase III, randomized, open-label, multicenter study to evaluate the efficacy and safety of BL-B01D1 in combination with osimertinib in patients with unresectable EGFR-mutated Stage III non-small cell lung cancer who have not progressed following platinum-based chemoradiotherapy.

Detailed description

In this trial, the treatment group receives BL-B01D1 in combination with osimertinib, while the control group receives osimertinib monotherapy.

Interventions

• Drug BL-B01D1
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Osimertinib
  Oral administration for a cycle of 3 weeks.

Primary outcome measures

• Progression-free survival (PFS) [Time frame: Up to approximately 24 months]

Secondary outcome measures (6)

• Overall Survival (OS) [Time frame: Up to approximately 24 months]
• Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Duration of Response (DOR) [Time frame: Up to approximately 24 months]
• Treatment Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Anti-drug antibody (ADA) [Time frame: Up to approximately 24 months]

Eligibility criteria

Inclusion criteria

• Voluntarily sign the informed consent form and comply with the protocol requirements;
• Age ≥ 18 years and ≤ 75 years, regardless of gender;
• Expected survival time ≥ 3 months;
• Unresectable Stage III non-small cell lung cancer;
• Detection of one of the EGFR-sensitive mutation types in tumor tissue;
• Agree to provide archived primary tumor tissue specimens or fresh tissue samples within 1 year;
• In platinum-based radical chemoradiotherapy, the platinum-containing chemotherapy regimen must include one of the specified drugs in addition to the platinum agent;
• In platinum-based radical chemoradiotherapy, patients must have received a total radiation dose of 60 Gy ± 10% before randomization;
• Toxicities from prior chemoradiotherapy must have resolved to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
• ECOG performance status score of 0 or 1;
• No severe cardiac dysfunction, with left ventricular ejection fraction ≥ 50%;
• Organ function levels must meet the requirements;
• Urine protein ≤ 1+ or < 1000 mg/24h;
• For premenopausal women with childbearing potential, a serum pregnancy test must be performed within 7 days before starting treatment, and the test must rule out pregnancy; they must not be lactating; all enrolled trial participants must take adequate barrier contraceptive measures throughout the treatment period and for 7 months after treatment ends.

Exclusion criteria

• SCLC, mixed SCLC and NSCLC, or other non-NSCLC pathological types;
• The trial participant has received other chemotherapy, radiotherapy, etc., for NSCLC apart from radical chemoradiotherapy;
• Major surgery within 4 weeks prior to the first dose;
• Prior treatment with ADC drugs using topoisomerase I inhibitors as toxins, or antibodies/ADCs targeting EGFR and/or HER3;
• History of severe heart disease or cerebrovascular disease;
• Prolonged QTc interval, complete left bundle branch block, second- or third-degree atrioventricular block, or frequent and uncontrolled arrhythmias;
• Any thrombotic events such as deep vein thrombosis, arterial thrombosis, or pulmonary embolism within 6 months prior to screening;
• Diagnosis of active malignancy within 5 years prior to study randomization;
• Hypertension poorly controlled by two antihypertensive medications;
• Trial participants with poorly controlled blood glucose levels;
• Current radiation pneumonitis of Grade ≥2 as defined by CTCAE;
• Concurrent lung disease resulting in clinically severe respiratory impairment;
• Severe infection within 4 weeks prior to study randomization;
• Large serous cavity effusions or symptomatic serous cavity effusions;
• Imaging findings suggesting tumor invasion or encasement of major blood vessels in the abdomen, chest, neck, or pharynx;
• Severe non-healing wounds, ulcers, or fractures within 4 weeks prior to signing informed consent;
• Trial participants with clinically significant bleeding or a clear tendency for bleeding within 4 weeks prior to signing informed consent;
• Trial participants with a history of inflammatory bowel disease, extensive bowel resection, or immune-mediated enteritis;
• History of allergy to recombinant humanized antibodies or chimeric human-mouse antibodies, or allergy to any excipient components of the investigational drug;
• History of autologous or allogeneic stem cell transplantation;
• Positive for human immunodeficiency virus antibodies, active hepatitis B virus infection, or hepatitis C virus infection;
• History of severe neurological or psychiatric disorders, or a history of substance abuse, alcoholism, or drug addiction;
• Trial participants planning to receive or having received live vaccines within 28 days prior to study randomization;
• Other conditions deemed by the investigator as unsuitable for participation in this clinical trial due to complications or other reasons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Cancer Hospital of Shandong First Medical University — Jinan

Identifiers

NCT: NCT07640789 · BL-B01D1-318

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗