Phase II Clinical Study of Adebrelimab Combined with Apatinib in the Treatment of Locally Advanced Non-small Cell Lung Cancer Patients with Radiation Pneumonitis

A Prospective, Single-center, Phase II Clinical Study of Adebrelimab Combined with Apatinib in the Treatment of Unresectable Stage III NSCLC Patients with Grade ≤2 Radiation Pneumonitis After Definitive Chemoradiotherapy

A prospective, single-center, phase II clinical study of adebrelimab combined with apatinib in the treatment of unresectable stage III NSCLC patients with grade ≤2 radiation pneumonitis after definitive chemoradiotherapy

Study Overview

• Status: Active, not recruiting
• Conditions: Unresectable Locally Advanced Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Adebrelimab + Apatinib

Detailed Description

A prospective, single-center, phase II clinical study of adebrelimab combined with apatinib in the treatment of unresectable stage III NSCLC patients with grade ≤2 radiation pneumonitis after definitive chemoradiotherapy.At least 32 participants will be enrolled in this study.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China
      • Chongqing University Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. ECOG PS score 0-1;
3. The expected survival time is not less than 12 weeks;
4. Histologically or cytologically confirmed non-small cell lung cancer patients with unresectable locally advanced (stage III) (AJCC TNM staging, 8th edition);
5. Patients who are not candidates for EGFR, ALK, or ROS1 targeted therapy, as confirmed by histologic or cytologic specimens (with documented evidence of no EGFR sensitizing mutation, ALK gene rearrangement, or ROS1 gene fusion);
6. Patients with grade 2 or below radiation pneumonitis without disease progression after receiving platinum-based concurrent/sequential chemoradiotherapy;
7. First dose was administered on days 1-42 (up to 42 days) after completion of concurrent/sequential platinum-based chemoradiotherapy for grade ≤1 RP; Patients with grade 2 RP who were downgraded to less than grade 1 RP within 56 days (including 56 days) after concurrent/sequential chemoradiotherapy received the first medication, and consolidation chemotherapy after radiotherapy was not allowed during the period.

All toxic effects from previous antineoplastic therapy, except hearing loss, alopecia, and fatigue, had to have recovered to grade 1 or less (according to NCI CTCAE V5.0) or baseline levels to be eligible.

9. Have not received any anti-CTLA-4, anti-PD-1, anti-PD-L1/2, anti-angiogenesis inhibitors, or anti-tumor vaccine therapy; 10. Provide or collect biopsy tissue or blood samples during the treatment for biomarker analysis according to the subjects' wishes; 11. Normal function of major organs and bone marrow; 12. Female subjects of childbearing potential had to have a negative serum or urine pregnancy test 72 hours before starting the trial and be willing to use a highly effective, medically approved contraceptive method for the duration of the study and for 90 days after the last dose of the trial drug; Male participants whose partner was a woman of childbearing potential agreed to use an effective method of contraception or to be surgically sterilized for the duration of the study and for 90 days after the last dose of the trial drug.

13. The subjects voluntarily participated in this study, and signed the informed consent form. The compliance was good, and the efficacy and adverse reactions were followed up according to the protocol.

Exclusion Criteria:

1. Histological types of mixed small cell lung cancer and non-small cell lung cancer;
2. Disease progression after chemoradiotherapy; Had undergone major surgery within 28 days before the first dose of a study drug or was planned to undergo major surgery during the study (at the investigator's discretion); 3.

4. Administration of live attenuated vaccine within 28 days prior to dose or planned for the duration of the study; 5. Participated in another clinical study within 28 days before the first use of a trial drug, and used any trial drug; 6. Grade ≥3 radiation pneumonitis caused by chemoradiotherapy; 7. Imaging (CT/MRI) showed that the tumor invaded the large blood vessels or had unclear boundaries with blood vessels; 8. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 9. Presence of any active autoimmune disease or a history of autoimmune disease with expected recurrence; 10. Congenital or acquired immune deficiency; 11. Suffering from an infectious disease that is poorly controlled; 12. Subjects requiring systemic treatment with corticosteroids (>10mg/ day of prednisone or equivalent dose of the same hormone) or other immunosuppressive agents within 14 days before the first dose of the trial drug; 13. Cancer other than NSCLC in the past 5 years; 14. Evidence of past or current severe impairment of lung function, with forced expiratory volume in 1 second (FEV1) <1.2L or DLCO<50% of predicted value; 15. Grade II or above myocardial ischemia or myocardial infarction with poorly controlled arrhythmia; 16. Have poorly controlled hypertension; 17. Occurrence of arterial/venous thrombotic events (cerebral embolism, deep vein thrombosis, pulmonary embolism, etc.) within 6 months before the first dose; 18. Subjects with clinically significant bleeding symptoms or clear evidence or history of bleeding tendency within 3 months before the first dose; 19. Obvious hemoptysis symptoms within 30 days before the first dose or hemoptysis of 2.5mL or more per day; 20. Known hereditary or acquired bleeding and thrombophilia (e.g. hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.); 21. Urine routine showed urine protein ≥ (++), or 24-hour urine protein ≥ 1.0g; 22. The need for systemic antibiotics due to infection within 14 days before the first dose of medication; Or unexplained fever > 38.5 ° C 14 days before the first dose of medication; 23. Pregnant or lactating women; 24. Known allergy or intolerance to the study drug or its excipients; 25. Any condition that the investigator considers may harm the subject or cause the subject to be unable to meet or perform the requirements of the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group A; Patients with grade 0-1 radiation pneumonitis were enrolled and treated with adebrelimab combined with apatinib within 42 days after definitive chemoradiotherapy	Drug: Adebrelimab + Apatinib; Adebrelimab combined with apatinib; Other Names: immunotherapy; Antiangiogenic agents; Programmed death ligand 1 inhibitor
Other: Group B; Patients with grade 2 radiation pneumonitis were enrolled and treated with adebrelimab combined with apatinib within 56 days after definitive chemoradiotherapy	Drug: Adebrelimab + Apatinib; Adebrelimab combined with apatinib; Other Names: immunotherapy; Antiangiogenic agents; Programmed death ligand 1 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Refers to the time from the start of nonrandomization until tumor progression or death from any cause, whichever occurs first	Doses were administered every 6 weeks from the first dose of study drug until approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival, OS	Refers to the time from the start of nonrandomization until death from any cause.	Doses were administered every 6 weeks from the first dose of study drug until approximately 12 months
Objective Response Rate, ORR	Refers to the proportion of patients who have achieved a pre-defined tumor volume reduction (CR/PR) and maintained the minimum time frame required by the accepted response evaluation criteria (such as solid tumor RECIST Version 1.1).	Doses were administered every 6 weeks from the first dose of study drug until approximately 12 months
Disease control rate, DCR	Proportion of all subjects whose best overall response (BOR) was rated as complete response (CR), partial response (PR), and stable disease (SD) according to RECIST v1.1 criteria.	Doses were administered every 6 weeks from the first dose of study drug until approximately 12 months
Duration of response, DOR	Defined as the period from the date the tumor remission was first recorded to the date the disease progression was first recorded or the date of death from any cause	Doses were administered every 6 weeks from the first dose of study drug until approximately 12 months

Collaborators and Investigators

• Sponsor: Wei Zhou
• Investigators: Principal Investigator: Wei Zhou, Chongqing University Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 20, 2024
• First Submitted That Met QC Criteria: November 20, 2024
• First Posted (Estimated): November 22, 2024

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Apatinib; Chemoradiotherapy; Radiation pneumonitis; Unresectable locally advanced non-small cell lung cancer; Adebrelimab
• Additional Relevant MeSH Terms: Wounds and Injuries; Neoplasms by Site; Neoplasms; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases, Interstitial; Carcinoma, Bronchogenic; Bronchial Neoplasms; Radiation Injuries; Lung Injury; Lung Neoplasms; Pneumonia; Carcinoma, Non-Small-Cell Lung; Radiation Pneumonitis; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Immune Checkpoint Inhibitors; Apatinib; Angiogenesis Inhibitors
• Other Study ID Numbers: MA-NSCLC-II-035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The survival data of individual participant will be shared after the research iscompleted.
• IPD Sharing Time Frame: After the study is completed.
• IPD Sharing Access Criteria: Other Medical Professionals with permission from Principle Investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

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