An Exploratory Clinical Study of Adebelimumab in Combination With Famitinib and Chemotherapy in Patients With NSCLC

NCT06332300 | Withdrawn Phase 2

• 1 other identifier: ADBL-LC-003
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study was a single-arm design to explore the efficacy and safety of Adebelimumab in combination with famitinib and lateral ventricular chemotherapy in patients with floppy meningeal metastases from non-squamous NSCLC who have failed EGFR-TKI therapy, and included patients with pathologically confirmed non-squamous non-small cell lung cancer.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• ORR

  Objective remission rates for flaccid meninges

  Two years of observation after enrollment

Secondary Outcomes (4)

• iPFS

  Two years of observation after enrollment

• iDoR

  Two years of observation after enrollment

• PFS

  Two years of observation after enrollment

• OS

  Two years of observation after enrollment

Study Arms (1)

Adebelimumab+famitinib+chemotherapy

EXPERIMENTAL

Adebelimumab in combination with famitinib and lateral ventricular chemotherapy in patients with non-squamous NSCLC with soft meningeal metastases who have failed EGFR-TKI therapy

Drug: Adebelimumab+Famitinib + FOLFIRI+Ariely

Interventions

Adebelimumab+Famitinib + FOLFIRI+Ariely DRUG

Adebelimumab in combination with famitinib and lateral ventricular chemotherapy in patients with non-squamous NSCLC with soft meningeal metastases who have failed EGFR-TKI therapy

Adebelimumab+famitinib+chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign the informed consent form (ICF)
• Aged 18-75 years old, male or female.
• Histologically or cytologically confirmed EGFR mutation-positive non-squamous NSCLC (International Association for the Study of Lung Cancer (IASLC) 8th edition TNM staging criteria)
• LM diagnosis confirmed by positive CSF cytology
• Re-biopsy (histology or cytology or hematology) after treatment failure with at least one EGFR tyrosine kinase inhibitor (EGFR-TKI) suggesting no EGFR-sensitive mutation and possibly other treatments
• All patients are required to have NSCLC associated with at least 1 LM site identified by the investigator that can be evaluated by MRI scanning and is amenable to repeat evaluation.
• not required to have received systemic corticosteroids (\>10mg/day prednisone or equivalent) within 2 weeks prior to enrollment
• Expected survival ≥ 12 weeks
• Vital organ function within 1 week before enrollment meets the following criteria: (1) blood routine: white blood cell (WBC) ≥3.0×109/L; absolute neutrophil count (ANC) ≥1.5×109/L; platelet (PLT) ≥100×109/L; hemoglobin (HGB) ≥9.0 g/Dl (2) Liver function: aspartate transferase (AST) ≤2.5×ULN, alanine aminotransferase (ALT) ≤2.5×ULN. (3) Renal function: serum creatinine ≤1.5×ULN or creatinine clearance rate (creatinine) ≤1.5×ULN; serum bilirubin (TBIL) ≤2.5×ULN, alanine aminotransferase (ALT) ≤2.5×ULN, and in liver metastasis ≤5×ULN; serum bilirubin (TBIL) ≤1.5×ULN (except for Gilbert Syndrome ≤3×ULN); albumin (ALB) ≥30.0g/L (3) Renal function: serum creatinine ≤1.5×ULN or creatinine clearance rate (creatinine) ≤1.5×ULN. (3) Renal function: serum creatinine ≤1.5×ULN or creatinine clearance rate (CrCl) ≥50 mL/minute (using the Cockcroft/Gault formula) (4) Coagulation function: international normalized ratio (INR) ≤1.5; activated partial coagulation time (APCT) ≥1.5; activated partial coagulation time (APCT) ≤1.5 (4) Coagulation function: international normalized ratio (INR) ≤1.5, activated partial thromboplastin time (APTT) ≤1.5×ULN (5) Others: lipase ≤1.5×ULN; if lipase \>1.5×ULN, the patient can be enrolled if there is no clinical or imaging evidence of pancreatitis; amylase ≤1.5×ULN; if amylase \>1.5×ULN, the patient can be enrolled if there is no clinical or imaging evidence of pancreatitis; amylase ≤1.5×ULN; and amylase ≤1.5×ULN. or imaging evidence of pancreatitis can be enrolled. Alkaline phosphatase (ALP) ≤ 2.5 x ULN, and in subjects with bone metastases, ALP ≤ 5 x ULN (6) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) ≥ 50%
• Female patients who are non-surgically sterilized or of childbearing potential must have a negative serum HCG test within 72 hours prior to the first dose of study medication and must not be lactating, and must agree to use appropriate contraception (e.g., intrauterine device (IUD), birth control pills, or condoms) during the study treatment period and for 3 months after the end of the study treatment period; male patients must agree to use appropriate contraceptive methods during the study treatment period and for 3 months after the end of the study treatment period. Male patients agree to use an appropriate method of contraception during and for 3 months after study treatment.

You may not qualify if:

• Patients with histologic or cytopathologic diagnosis of adenosquamous carcinoma or complex SCLC.
• Genetic tests suggesting ALK fusion, ROS1 fusion, BRAF mutation, ERBB2 (HER2) amplification/mutation, RET rearrangement, MET amplification/MET14 exon jumping mutation and NTRK fusion positivity.
• Clinical manifestations of neurologic failure such as severe encephalopathy or treatment-related severe neurologic injury, such as chemical meningitis
• Non-malignant neurologic diseases that would interfere with the evaluation of LM signs or symptoms
• radiotherapy directed to the chest and whole brain completed within 4 weeks prior to enrollment (palliative radiotherapy to bone lesions completed prior to the first dose of study drug is permitted for enrollment)
• toxicity due to prior antitumor therapy other than alopecia and malaise not recovered to CTCAE 5.0 ≤ grade 1 prior to enrollment. Some other toxicities due to prior antitumor therapy are not expected to resolve within the expected period and have long-term persistent sequelae
• patients with spinal cord compression that has not been cured or relieved by surgery and/or radiotherapy, or patients with previously diagnosed spinal cord compression that has been treated with compression insufficiency or total paralysis; patients with liver metastases who have received cryo- and radiofrequency ablation therapy and who still have clinically significant symptoms and abnormal hepatic function in the 4 weeks prior to enrollment
• Presence of uncontrollable large amount of pleural effusion, pericardial effusion or ascites.
• Presence of the following cardiac diseases: (1) cardiac function class III-IV according to NYHA cardiac function classification (2) unstable angina pectoris or electrocardiogram suggesting acute ischemia or myocardial infarction within 1 year (3) clinically significant supraventricular or ventricular arrhythmia and other conduction system abnormalities (including QTc interval greater than or equal to 450ms for men and ≥470ms for women) (4) clinically significant Pericardial and myocardial diseases
• Inadequate bone marrow reserve or organ function
• Treatment with systemic immunomodulators (including but not limited to thymidine, interferon, or interleukin-2) within 4 weeks prior to enrollment
• Any active autoimmune disease or history of autoimmune disease; interstitial pneumonitis, drug-induced pneumonitis, radiation pneumonitis requiring steroid therapy, or active pneumonia with clinical symptoms
• active or uncontrolled serious infection (CTCAE 5.0 ≥ grade 2) and/or antibiotic treatment within 2 weeks prior to enrollment
• Patients with active or undergoing treatment for tuberculosis
• Uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg), history of hypertensive crisis or hypertensive encephalopathy

Sponsors & Collaborators

• Jiangsu Province Nanjing Brain Hospital: lead

Study Sites (1)

Shengcun Fang

Nanjing, Jiangsu, China

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2024
• First Posted: March 27, 2024
• Study Start: February 1, 2024
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2026
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)