A Study Evaluating BL-B01D1 in Combination With a PD-1/VEGF Bispecific Antibody Versus Tislelizumab Plus Platinum-doublet Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer(PANKU-Lung06)

Official title

A Randomized, Open-label, Multicenter Phase II/III Clinical Study Evaluating BL-B01D1 in Combination With a PD-1/VEGF Bispecific Antibody Versus Tislelizumab Plus Platinum-doublet Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer(PANKU-Lung06)

Overview

This trial is a registrational randomized, open-label, multicenter Phase II/III study designed to evaluate the efficacy and safety of BL-B01D1 in combination with a PD-1/VEGF bispecific antibody in patients with locally advanced or metastatic non-squamous non-small cell lung cancer.

Interventions

• Drug BL-B01D1
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug PD-1/VEGF Bispecific Antibody
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Tislelizumab
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Pemetrexed
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Carboplatin
  Administration by intravenous infusion for a cycle of 3 weeks.
• Drug Cisplatin
  Administration by intravenous infusion for a cycle of 3 weeks.

Primary outcome measures

• Phase II: Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Phase II: Investigator-assessed Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]
• Phase III: BICR-assessed Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]
• Phase III: Overall Survival (OS) [Time frame: Up to approximately 24 months]

Secondary outcome measures (12)

• Phase II/III: Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Phase II/III: Duration of Response (DOR) [Time frame: Up to approximately 24 months]
• Phase II/III: Treatment Emergent Adverse Event (TEAE) [Time frame: Up to approximately 24 months]
• Phase III: Progression-free Survival (PFS) [Time frame: Up to approximately 24 months]
• Phase III: BICR and Investigator-assessed Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Phase III: Cmax [Time frame: Up to approximately 24 months]
• Phase III: Tmax [Time frame: Up to approximately 24 months]
• Phase III: T1/2 [Time frame: Up to approximately 24 months]
• Phase III: AUC0-t [Time frame: Up to approximately 24 months]
• Phase III: CL (Clearance) [Time frame: Up to approximately 24 months]
• Phase III: Ctrough [Time frame: Up to approximately 24 months]
• Phase III: 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;
• Expected survival time ≥ 3 months;
• Patients with locally advanced non-squamous non-small cell lung cancer;
• Agree to provide tumor tissue samples obtained at or after diagnosis of locally advanced or metastatic cancer;
• Must have at least one measurable lesion as defined by RECIST v1.1;
• ECOG performance status score of 0 or 1;
• Toxicities from prior anti-tumor therapy have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0;
• No severe cardiac dysfunction, with left ventricular ejection fraction ≥ 50%;
• Organ function levels must meet the required criteria;
• Urinary protein ≤ 2+ or < 1000 mg/24h;
• For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before starting treatment; serum pregnancy test must rule out pregnancy; patients must be non-lactating and must use highly effective contraceptive measures throughout the treatment period and for 7 months after the last dose. For male participants whose partners are women of childbearing potential, adequate barrier contraceptive measures must be used throughout the treatment period and for 7 months after the end of treatment.

Exclusion criteria

• Presence of small cell lung cancer, neuroendocrine carcinoma, sarcomatoid carcinoma components, or squamous carcinoma components exceeding 10%;
• Evidence suggesting the presence of EGFR-sensitive mutations, etc.;
• Patients who have received prior systemic therapy;
• Prior receipt of therapies targeting the mechanism of tumor immunity;
• Prior receipt of antibody-drug conjugates (ADCs) using topoisomerase I inhibitors as the toxin, etc.;
• Trial participants who have received prior systemic anti-angiogenic therapy;
• Receipt of radical radiotherapy, major surgery, or large-field radiotherapy within 4 weeks before study randomization;
• History of severe cardiac or cerebrovascular disease;
• Receiving long-term systemic corticosteroid therapy (e.g., >10 mg/day prednisone) prior to the first dose;
• Active autoimmune diseases and inflammatory diseases;
• Unstable thrombotic events requiring therapeutic intervention within 6 months before screening;
• Prolonged QT interval, complete left bundle branch block, etc.;
• Diagnosis of active malignancy within 3 years before study randomization;
• Hypertension poorly controlled by two antihypertensive medications;
• Patients with poorly controlled blood glucose;
• History of ILD requiring steroid therapy, current ILD, or ≥ grade 2 radiation pneumonitis, etc.;
• Concurrent pulmonary diseases resulting in clinically severe impairment of respiratory function;
• Patients with active central nervous system metastases;
• Occurrence of severe infection within 4 weeks before study randomization;
• Presence of large serous cavity effusions, or symptomatic serous cavity effusions, etc.;
• Imaging findings suggesting tumor invasion or encasement of abdominal, thoracic, or other regions;
• Presence of serious non-healing wounds, ulcers, or fractures within 4 weeks before signing informed consent;
• Trial participants with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing informed consent;
• Patients with a history of inflammatory bowel disease, extensive bowel resection, immune-mediated enteritis, intestinal obstruction, or chronic diarrhea, etc.;
• History of allergy to recombinant humanized antibodies or allergy to the investigational drug, etc.;
• History of autologous or allogeneic stem cell transplantation;
• Positive for human immunodeficiency virus antibody, active hepatitis B virus infection, or hepatitis C virus infection;
• History of severe neurological or psychiatric disorders;
• Receipt of other unapproved investigational drugs or treatments within 4 weeks before study randomization;
• Trial participants who plan to receive or have received live vaccines within 28 days before study randomization;
• Other conditions that, in the investigator's opinion, make the patient unsuitable for participation in this clinical trial due to complications or other circumstances.

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 · 2 centers

• Sun Yat-sen University Cancer Center — Guangzhou
• The First Affiliated Hospital of Guangzhou Medical University — Guangzhou

Identifiers

NCT: NCT07739186 · BL-B01D1-313

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗