Adebrelimab Combined With Bevacizumab and Albumin Paclitaxel in Non-squamous NSCLC After First-line Treatment

A Prospective, Single-arm, Phase II Trial of Adebrelimab Combined With Bevacizumab and Albumin Paclitaxel in Advanced Non-squamous Non-small Cell Lung Cancer After First-line Immunotherapy Progression

A prospective, single-arm, phase II trial of Adebrelimab combined with bevacizumab and albumin paclitaxel in advanced non-squamous non-small cell lung cancer after first-line immunotherapy progression.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Adebrelimab Combined With Bevacizumab and Albumin Paclitaxel

Detailed Description

The study consisted of a screening period (no more than 4 weeks after patients signed informed consent until enrollment, with imaging assessments allowed to be archived within 4 weeks prior to enrollment), a treatment period (treatment termination defined as discontinuation of treatment for any reason, or withdrawal from the study for any reason), a safety follow-up period, and a survival follow-up period.

Screening period:

Patients were required to undergo a screening evaluation to determine their eligibility for the study within 4 weeks prior to enrollment.

Patients eligible for the study receive adebrelimab, 20 mg/kg, Intravenous infusion, Q3W + bevacizumab, 7.5 mg/kg, Intravenous infusion, Q3W + albumin paclitaxel 100 mg/m2, D1, 8, 15, Intravenous infusion, Q3W. albumin paclitaxel treatment for 4 cycles, adebrelimab, bevacizumab use to PD, intolerable toxicity, patient withdrawal of informed consent, investigator decision to discontinue study treatment.

Treatment period:

Patients eligible for study enrollment were given medication sequentially on day 1 of each cycle, with a dosing window of ±5 days, and patients were required to complete various examinations including vital signs, height and weight, physical examination, laboratory tests, and physical status scores to assess tolerance for continued treatment. The specific examinations and requirements for each visit are shown in the study flow chart.

End of treatment:

End of treatment is defined as confirmation of disease progression or withdrawal from the study and requires an end-of-treatment visit ±5 days from the time of the decision to discontinue treatment and/or withdraw from the study.

Safety follow-up. Safety follow-up visits will be conducted within 30±7, 60±7 days, and 90±7 days after the last dose.

Survival follow-up. Survival follow-up will be conducted every 3 months after safety follow-up and telephone follow-up is acceptable.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaorong Dong, Dr.; Phone Number: 13986252286; Email: xiaorongdong@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Union Hospital
      • Contact: Xiaorong Dong, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. voluntarily enrolled in this study and signed the Informed Consent Form (ICF).
2. age ≥ 18 years and both sexes
3. patients with metastatic or recurrent stage IV non-squamous NSCLC (AJCC 8th edition TNM stage) proven by histopathological or cytopathological diagnosis, mainly including adenocarcinoma, large cell lung cancer, adenocarcinoma with squamous differentiation or adenosquamous carcinoma with predominantly adenocarcinoma component may also be enrolled if eligible by study assessment.
4. objective imaging progression (RECIST v1.1 assessment) after subjects have received a first-line regimen containing immune checkpoint inhibitor therapy.
5. the best outcome of first-line immune checkpoint inhibitor-containing therapy is SD, PR, CR, and PFS of ≥ 3 months on first-line therapy.
6. imaging evaluation (CT or MRI) with at least one measurable target lesion (according to RECIST v1.1 criteria) within 4 weeks prior to enrollment.
7. an ECOG PS score of 0-1 within 4 weeks prior to enrollment.
8. an expected survival of ≥ 12 weeks.
9. function of vital organs in accordance with the following requirements. (1) blood routine: white blood cell count (WBC) ≥ 3.0×109/L; absolute neutrophil count (ANC) ≥ 1.5×109/L; platelets (PLT) ≥ 100×109/L; hemoglobin level (HGB) ≥ 9.0 g/dL (no corresponding supportive treatment such as blood transfusion and leukocyte boosting within 7 days).

(2) Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN in patients without liver metastases, ALT and AST ≤ 5 times ULN in patients with liver metastases; serum total bilirubin (TBIL) ≤ 1.5 times ULN (except total bilirubin < 3.0 mg/dL in Gilbert syndrome); albumin (ALB) ≥ 30 g/L, alkaline phosphatase (ALP) ≤ 2.5×ULN, and in patients with bone metastases, ALP ≤ 5×ULN.

(3) renal function: serum creatinine ≤ 1.5 times ULN or creatinine clearance (CrCl) ≥ 50 mL/min (using Cockcroft/Gault formula); urine protein (UPRO) < (++), or 24-hour urine protein amount < 1.0 g.

(4) Coagulation function: international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN; if the patient is receiving anticoagulation therapy, as long as PT or APTT is within the therapeutic range of the intended use of anticoagulants, referring to the relevant drug instructions.

(5) Thyrotropin (TSH) ≤ upper limit of normal (ULN); if abnormal, T3 and T4 levels should be examined; normal T3 and T4 levels are eligible for enrollment.

10. Non-surgical sterilization or female patients of childbearing age must have a negative serum pregnancy test within 7 days prior to the first dose and must be non-lactating. Female patients of childbearing age or male patients whose partners are women of childbearing age must agree to use highly effective methods of contraception during the study period and for 6 months after the last administration of the study drug.

Exclusion Criteria:

1. patients with other pathological tissue types of non-small cell lung cancer (including squamous cell carcinoma, mixed non-small cell and small cell lung cancer, and predominantly squamous adenosquamous carcinoma of the lung)
2. patients with known EGFR-sensitive mutations (19Exon del/21Exon L858R), positive ALK/ROS1 fusion, BRAFV600E mutation, MET gene exon 14 jump mutation, positive RET gene fusion, and other patients with approved targets for targeted agents.
3. patients with imaging showing signs of tumor invasion into the great vessels, where the tumor has completely approached, encircled, or invaded the lumen of a great vessel (e.g., pulmonary artery or superior vena cava)
4. patients with hypertension whose blood pressure is not satisfactorily controlled by antihypertensive medication (sitting systolic blood pressure > 150 mmHg, or diastolic blood pressure > 100 mmHg), previous hypertensive crisis or hypertensive encephalopathy
5. those with a known hereditary bleeding tendency or coagulation disorders; those who have received full-dose anticoagulant or thrombolytic therapy within 10 days prior to enrollment, or those who have taken non-steroidal anti-inflammatory drugs with platelet inhibitory effects within 10 days prior to enrollment (except for prophylactic use of low-dose aspirin (≤325 mg/day)).
6. had a hemoptysis of 2nd degree or greater with a single hemoptysis of ≥1/2 teaspoon (2.5 ml) within 3 months prior to enrollment
7. thrombosis in the 6 months prior to enrollment and an arterial/venous thrombotic event within 1 year prior to screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and pulmonary embolism.
8. those with severe vascular lesions (including aneurysms or arterial thrombosis requiring surgical treatment) within 6 months prior to enrollment
9. late first-line treatment with anti-angiogenic agents, including but not limited to bevacizumab, apatinib, anlotinib, ramucirumab, lenvatinib, etc.; treatment with paclitaxel, including paclitaxel, albumin paclitaxel, paclitaxel liposome, docetaxel (polyene paclitaxel), etc;

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: Adebrelimab Combined With Bevacizumab and Albumin Paclitaxel; Adebrelimab: 20 mg/kg Adebrelimab is given on day 1 of each cycle, with 1 dosing cycle every 3 weeks. The dosing time window may be ±5 days, but within 72 hours before each dose, subjects must complete an examination including all clinically necessary tests to assess tolerability of continued dosing, in addition to imaging. Subjects are also advised to remain in the hospital for observation 72 hours after the first dose. Bevacizumab: 7.5 mg/kg Bevacizumab administered intravenously on day 1 of each cycle, with 1 dosing cycle every 3 weeks. Albumin Paclitaxel: 100 mg/m2 Albumin Paclitaxel is given on days 1, 8, and 15 of each cycle by intravenous infusion for 1 dosing cycle every 3 weeks.

Drug: Adebrelimab Combined With Bevacizumab and Albumin Paclitaxel; Adebrelimab is recommended to be administered with an infusion pump. The infusion pipeline is equipped with a 0.22-micron online filter membrane. Intravenous injection or bolus injection is not allowed. At the end of infusion, flush the infusion tube with sufficient 5% glucose or physiological saline, and do not share the same infusion tube with other drugs. In each treatment cycle, Adebrelimab should be given intravenously first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month PFS rate	6-Month PFS Rates for Adebrelimab Combined with Bevacizumab and Albumin Paclitaxel in Patients with Advanced NSCLC Progressed by First-Line Immunotherapy Evaluated by Investigators	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS is defined as the time elapsed between the start of treatment and the first sign of disease progression or death from any cause.	up to 12 months
Over survival (OS)	OS is defined as the time elapsed between the initiation of treatment and mortality from any cause.	up to 12 months
Disease control rate (DCR)	Number of cases with completed/partial response and stable disease after treatment as a percentage of evaluable cases.	up to 12 months

Collaborators and Investigators

• Sponsor: Xiaorong Dong
• Investigators: Study Chair: Xiaorong Dong, Dr., Wuhan Union Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: February 12, 2023
• First Submitted That Met QC Criteria: February 20, 2023
• First Posted (Estimate): February 22, 2023

Study Record Updates

• Last Update Posted (Estimate): February 22, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Paclitaxel; Bevacizumab
• Other Study ID Numbers: MA-NSCLC-II-026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to make individual participant data (IPD) available to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No