Using Circulating Tumor DNA to Personalize Duration of Consolidation Durvalumab

Phase 2

Recruiting

• Conditions: NSCLC, Stage III
• Interventions: Diagnostic Test: Signatera ctDNA test; Drug: Durvalumab

• Registration Number: NCT05757843
• Lead Sponsor: Indiana University

Brief Summary

This research aims to incorporate ctDNA analysis into clinical practice to individualize therapy in patients with stage III NSCLC by moving to a treatment-by-marker based approach (as opposed to treatment based on clinical or radiographic evidence of disease).

Detailed Description

There is a critical need to identify MRD to determine which patients benefit from checkpoint inhibitor therapy and to optimize and personalize the duration of consolidation Durvalumab. The long-term goal is to incorporate ctDNA analysis into clinical practice to individualize therapy in patients with stage III NSCLC by moving to a treatment-by-marker based approach (as opposed to treatment based on clinical or radiographic evidence of disease). This approach may spare a subset of patients from treatment with unnecessarily excessive cycles of consolidation immunotherapy if they are already cured with CRT alone and individualize the duration of consolidation immunotherapy in patients not cured with CRT. The study team also seek to identify early in the treatment course, patients who are destined not to be cured with consolidation immunotherapy so that alternative strategies can be tested when tumor burden is low.

Study Timeline

• Study First Submitted: 2023-02-24
• Study First Submitted QC: 2023-02-24
• Study First Posted: 2023-03-07
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-06
• Last Update Posted: 2024-08-09
• Study Start: 2024-09
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

Age ≥ 18 years

Ability to provide written informed consent and HIPAA authorization

Patients with inoperable or unresectable stage III NSCLC who are planning to receive concurrent CRT followed by consolidation Durvalumab OR Patients with inoperable or unresectable stage III NSCLC who have previously received concurrent CRT and are planning or currently receiving C1-4 consolidation durvalumab

Must have viable tissue for ctDNA profiling, (fresh or archived tissue)

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Exclusion Criteria

Patient unwilling to provide tissue and blood samples for ctDNA testing.

Patient has contraindications to treatment with concurrent CRT and/or consolidation Durvalumab.

Patients with any other active cancer; excluding squamous cell or basal cell cancer.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Consolidation to Durvalumab	Signatera ctDNA test	All subjects will receive consolidation Durvalumab approximately every 4 weeks. The first mandatory ctDNA test will be done at screening for the bespoke ctDNA profiling. The next mandatory ctDNA test will be completed prior to the 5th cycle of consolidation Durvalumab. If it's negative and the subsequent test 4 weeks later prior to cycle 6 is negative, then Durvalumab will be stopped otherwise subject will continue consolidation durvalumab until 2 negative ctDNA analyses performed approximately 4 weeks apart or up to 1 year of consolidation per standard medical practice is complete.
Consolidation to Durvalumab	Durvalumab	All subjects will receive consolidation Durvalumab approximately every 4 weeks. The first mandatory ctDNA test will be done at screening for the bespoke ctDNA profiling. The next mandatory ctDNA test will be completed prior to the 5th cycle of consolidation Durvalumab. If it's negative and the subsequent test 4 weeks later prior to cycle 6 is negative, then Durvalumab will be stopped otherwise subject will continue consolidation durvalumab until 2 negative ctDNA analyses performed approximately 4 weeks apart or up to 1 year of consolidation per standard medical practice is complete.

Primary Outcome Measures

Name	Time	Method
Determine if de-escalating number of Durvalumab cycles based on personalized ctDNA clearance has non-inferior 2-year PFS rate	Baseline to 24 months	Determine if de-escalating the number of Durvalumab cycles based on personalized ctDNA clearance guidance to at least 6 cycles after CRT in stage III non-resectable NSCLC has non-inferior 2-year PFS rate compared with historical control of empirically treating stage III non-resectable NSCLC for 1 year of Durvalumab after CRT.

Secondary Outcome Measures

Name	Time	Method
Estimate the 24-month overall survival (OS) of patient treated with consolidation Durvalumab based on personalized ctDNA clearance	Baseline to 24 months	Estimate the 24-month overall survival (OS) of patient treated with consolidation Durvalumab based on personalized ctDNA clearance guidance for at least 6 cycles after CRT in stage III non-resectable NSCLC.
Estimate the 24-month PFS in patients with persistently detectable ctDNA without radiographic progression	Baseline to 24 months	Estimate the 24-month PFS in patients with persistently detectable ctDNA without radiographic progression of disease after receiving ≥ 6 months of consolidation Durvalumab.

Trial Locations

Locations (1)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center; 🇺🇸 Indianapolis, Indiana, United States