NCT06732401

Testing the Addition of AZD6738 (Ceralasertib) to Immunotherapy to Increase Time Without Cancer for Patients With Non-Small Cell Lung Cancer

A Randomized Phase III Trial of Checkpoint Blockade in Lung Cancer Patients in the Adjuvant Setting Based on Pathologic Response Following Neoadjuvant Therapy (CLEAR)

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 630 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase III trial compares the effect of adding AZD6738 to durvalumab versus durvalumab alone to increase time without cancer in patients with non-small cell lung cancer, following treatment with chemotherapy and surgery. AZD6738 may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Adding AZD6738 to durvalumab may increase time without cancer in patients with non-small cell lung cancer, following treatment with chemotherapy and surgery.

Detailed description

PRIMARY OBJECTIVE: I. To assess for improvement in disease free survival (DFS) in patients who do not achieve pathologic complete response (pCR) following neoadjuvant therapy and patients who receive adjuvant combination immunotherapy with durvalumab and AZD6738 (ceralasertib) compared to those who receive monotherapy with durvalumab. SECONDARY OBJECTIVE: I. To evaluate any difference in overall survival (OS) with patients who receive durvalumab and AZD6738 (ceralasertib) compared to those who receive monotherapy with durvalumab. EXPLORATORY OBJECTIVES: I. To evaluate any difference in disease free survival (DFS) with patients who receive durvalumab and AZD6738 (ceralasertib) compared to those who receive monotherapy with durvalumab according to PD-L1, stage, prior immune checkpoint inhibitor (ICI) type, and histology. II. To evaluate any difference in overall survival (OS) with patients who receive durvalumab and AZD6738 (ceralasertib) compared to those who receive monotherapy with durvalumab according to PD-L1, stage, prior ICI type, and histology. CORRELATIVE OBJECTIVE: I. To perform correlative analyses on tissue and blood biospecimens collected within this trial. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Starting 4-12 weeks after surgery, patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and blood sample collection throughout the study and may undergo echocardiography as clinically indicated. ARM B: Starting 4-12 weeks after surgery, patients receive AZD6738 orally (PO) twice daily (BID) on days 1-7 and durvalumab IV over 60 minutes on day 8 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan and blood sample collection throughout the study and may undergo echocardiography as clinically indicated. After completion of study treatment, patients are followed up every 12 weeks for 2 years then every 24 weeks until year 5 then every 12 months until 10 years from randomization.

Conditions

• Lung Non-Small Cell Carcinoma
• Stage II Lung Cancer AJCC v8
• Stage IIIA Lung Cancer AJCC v8
• Stage IIIB Lung Cancer AJCC v8

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
DRUG	Ceralasertib	Given PO
PROCEDURE	Computed Tomography	Undergo CT scan
BIOLOGICAL	Durvalumab	Given IV
PROCEDURE	Echocardiography Test	Undergo echocardiography

Timeline

• Start date: 2025-08-07
• Primary completion: 2028-06-30
• Completion: 2028-06-30
• First posted: 2024-12-13
• Last updated: 2026-04-13

Locations

193 sites across 1 country: United States

Regulatory

• FDA-regulated drug study