Immunotherapy After Surgery for People Who Have No Remaining Cancer Cells After Standard Treatment for Early-Stage Non-Small Cell Lung Cancer, INSIGHT Trial

THE STUDY

About this study

This phase III trial compares durvalumab to the usual approach (patient observation) after surgery for the treatment of patients with early-stage non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. The usual approach for patients who are not in a study is to closely watch a patient's condition after surgery and to have regular visits with their doctor to watch for signs of the cancer coming back. Usually, patients do not receive further treatment unless the cancer returns. This study will help determine whether this different approach with durvalumab is better, the same, or worse than the usual approach of observation. Giving durvalumab may help patients live longer and prevent early-stage non-small cell lung cancer from coming back as compared to the usual approach.

Full official title

Randomized Phase III Trial INcorporating Pathologic Complete ReSponse in Participants With Early StaGe Non Small Cell Lung Cancer to Optimize ImmunotHerapy in The AdjuvanT Setting (INSIGHT)

Detailed description

PRIMARY OBJECTIVE:

I. To compare disease free survival (DFS) in stage II-IIIB non-small cell lung cancer participants who achieved a pathologic complete response (pCR) following standard of care neoadjuvant chemo-immunotherapy and are randomized to adjuvant durvalumab (MEDI4736) versus surveillance.

SECONDARY OBJECTIVES:

I. To compare the overall survival (OS) between the arms. II. To evaluate the frequency and severity of toxicities of adjuvant durvalumab (MEDI4736).

III. To compare the event free survival (EFS) between the arms.

TRANSLATIONAL MEDICINE OBJECTIVE:

I. To bank specimens and images for additional future translational medicine studies.

QUALITY OF LIFE (QOL) PRIMARY OBJECTIVE:

I. To compare patient-reported quality of life (QOL) status between treatment arms at 6 months from randomization using the Functional Assessment of Cancer Therapy-Lung (FACT-L) Trial Outcome Index (TOI).

QOL SECONDARY OBJECTIVES:

I. To compare patient-reported QOL between treatment arms at 24 weeks (6 months) from randomization using the Functional Assessment of Cancer Therapy-Biologic Response Modifier (FACT-BRM) physical and mental subscale scores.

II. To compare longitudinal changes in global health status between treatment arms from randomization to 48 week (12 months) using the FACT-L TOI.

PATIENT REPORTED OUTCOMES-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE) OBJECTIVE:

I. To compare participant-reported symptoms using selected PRO-CTCAE items between treatment arms such as rash, itching, skin dryness, numbness, and tingling.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) and blood sample collection throughout the trial.

ARM II: Patients undergo active surveillance for 12 months on study. Patients undergo CT and blood sample collection throughout the trial.

After completion of study treatment, patients are followed up annually until 10 years from randomization.

PARTICIPATION

Who may participate

Minimum age: 18 Years
Maximum age: Not reported
Sex eligibility: All sexes
Healthy volunteers: Not accepted

Only the study team can confirm eligibility. The registry criteria below are not a medical recommendation.

Full inclusion and exclusion criteria

Recruiting

Albuquerque, New Mexico, 87106, United States

Site contacts (2)

Site Public ContactContactPhone: 505-925-0348Email: HSC-ClinicalTrialInfo@salud.unm.edu

Recruiting

Wisconsin Rapids, Wisconsin, 54494, United States

Site contacts (2)

Site Public ContactContactPhone: 715-422-7718

Andrew J. HuangPrincipal investigator

WHAT IS BEING STUDIED

Treatments and study groups

Interventions

Biospecimen CollectionProcedure

Undergo blood sample collection

Study groups: Arm I (durvalumab), Arm II (active surveillance)

Other names: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Computed TomographyProcedure

Undergo CT

Study groups: Arm I (durvalumab), Arm II (active surveillance)

Other names: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

DurvalumabBiological

Given IV

Study groups: Arm I (durvalumab)

Other names: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736, MEDI4736

Patient ObservationOther

Undergo active surveillance

Study groups: Arm II (active surveillance)

Other names: Active Surveillance, deferred therapy, expectant management, Observation, Watchful Waiting

Questionnaire AdministrationOther

Ancillary studies

Study groups: Arm I (durvalumab), Arm II (active surveillance)

Study groups

Arm I (durvalumab)Experimental

Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT and blood sample collection throughout the trial.

Interventions: Procedure: Biospecimen Collection, Procedure: Computed Tomography, Biological: Durvalumab, Other: Questionnaire Administration

Arm II (active surveillance)Active comparator

Patients undergo active surveillance for 12 months on study. Patients undergo CT and blood sample collection throughout the trial.

Interventions: Procedure: Biospecimen Collection, Procedure: Computed Tomography, Other: Patient Observation, Other: Questionnaire Administration

RESEARCH DETAILS

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Study model: Parallel
Masking: None (open label)
Enrolment: 306 participants · Estimated

TIMELINE & MEASURES

Dates and outcomes

Study started: 1 Apr 2025 · Actual
Primary completion: 15 Jul 2039 · Estimated
Study completion: 15 Jul 2039 · Estimated
First registered: 12 Jul 2024 · Actual
Last registry update: 19 Oct 2026 · Actual
Status last verified: Oct 2026

Primary outcomes (1)

Disease-free survival (DFS)

Will be assessed using a 1-sided 5% level log-rank test accounting for interim testing, stratified on the randomization stratification factors.

Time frame: From date of randomization to the earliest event defined as date of first documentation of recurrence, any new lung cancer (even in the contralateral lung), or death due to any cause, assessed up to 10 years

Secondary outcomes (3)

Event-free survival (EFS)

EFS events are defined as: Discontinuation of durvalumab (MEDI4736) due to toxicity, either immune or non-immune related, any new lung cancer (even in the contralateral lung), the use of glucocorticoids for \> 14 days for the treatment of toxicity secondary to durvalumab (MEDI4736), hospitalization due to toxicity from durvalumab (MEDI4736), disease recurrence, or death due to any cause. Will be estimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley. Hazard ratios (HRs) and corresponding 90% confidence intervals (CI) will be estimated using a Cox proportional hazards model with treatment arm as a single covariate. EFS will be compared between treatment arms using log-rank test, stratified on the randomization stratification factors.

Time frame: From date of randomization to date of first occurrence of EFS event, assessed up to 10 years

Overall survival (OS)

Will be estimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley. HRs and corresponding 90% CI will be estimated using a Cox proportional hazards model with treatment arm as a single covariate. OS will be compared between treatment arms using log-rank test, stratified on the randomization stratification factors.

Time frame: From date of randomization to date of death due to any cause, assessed up to 10 years

Incidence of adverse events

Will be evaluated using the Common Terminology Criteria for Adverse Events version 5 items. Binary proportions and associated confidence intervals will be calculated.

Time frame: Up to 10 years

Other outcomes (2)

Patient reported outcomes

Will be assessed by Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE) instrument(s). For each of the PRO-CTCAE adverse events examined, the scores for each attribute (frequency, severity and/or interference) will be presented descriptively using summary statistics at each assessment time. Additionally, the worst severity and/or interference over the entire course will be summarized.

Time frame: Up to 10 years

Estimates of the primary outcome treatment effect

The hazard ratio of DFS and the corresponding 95% CIs will be estimated for subgroups defined by sex, race and ethnicity, respectively.

Time frame: Up to 10 years

STUDY TEAM

Sponsor and contacts

Lead sponsor: National Cancer Institute (NCI)
Sponsor type: Nih
Collaborators: Not reported
Organisation study ID: NCI-2024-05588

Central study contacts

No central contact is currently reported. Check the site contacts or the official record.

Study officials

Jeremy P CetnarPrincipal investigator · SWOG Cancer Research Network

Contacts are provided by the registry for study enquiries. Do not use these details for marketing or promotions.

Results, documents and references

No results are posted in this registry record

This does not mean the study has no findings. Results may not yet have been submitted or published here.

No study documents are listed in this record.

Publications (1)

Osarogiagbon RU, Cetnar JP, Aljumaily R. Optimal Use of Targeted Therapy and Immunotherapy in Early-Stage, Resectable Non-Small Cell Lung Cancer. Am Soc Clin Oncol Educ Book. 2026 Jun;46(3):e518244. doi: 10.1200/EDBK-26-518244. Epub 2026 Jun 23. PubMed ↗