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)

Plain English Summary

Immunotherapy After Surgery for People Who Have No Remaining Cancer Cells After Standard Treatment for Early-Stage Non-Small Cell Lung Cancer, INSIGHT Trial is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8. This trial tests if adding an immunotherapy drug called durvalumab after surgery can help prevent early-stage lung cancer from returning. It is for patients who have had surgery for early-stage non-small cell lung cancer and no longer have cancer cells in their removed tissue. Participation involves receiving durvalumab or being closely monitored after surgery. The alternative is standard observation without additional treatment unless the cancer returns. The trial aims to enroll 306 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with early-stage non-small cell lung cancer (stages II-IIIB) who have had surgery. Must have no remaining cancer cells after surgery and have completed specific pre-surgery chemotherapy and immunotherapy. Must be 18 years or older and have good general health. Cannot have certain other medical conditions or have received specific prior treatments. This trial is studying Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary goal is to see if patients live longer without their cancer returning (disease-free survival) when they receive immunotherapy after surgery compared to standard observation. The specific primary outcome measures are: Disease-free survival (DFS) (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). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need to improve outcomes for early-stage lung cancer patients by exploring if immunotherapy after surgery can prevent recurrence, filling a gap in current treatment str As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Lung Non-Small Cell Carcinoma, Stage II Lung Cancer AJCC v8, Stage IIIA Lung Cancer AJCC v8, Stage IIIB Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

This trial, sponsored by the National Cancer Institute, investigates a post-surgical immunotherapy approach for a significant patient population, potentially impacting the adjuvant lung cancer treatme Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, considering your specific cancer stage and treatment history. Participation involves receiving the study drug (durvalumab) or being closely monitored by your medical team. You will have regular check-ups and tests to monitor your health and cancer status throughout the trial. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 306 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood sample collection
• PROCEDURE: Computed Tomography — Undergo CT
• BIOLOGICAL: Durvalumab — Given IV
• OTHER: Patient Observation — Undergo active surveillance
• OTHER: Questionnaire Administration — Ancillary studies

Primary Outcomes

• Disease-free survival (DFS) (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

• Event-free survival (EFS) (From date of randomization to date of first occurrence of EFS event, assessed up to 10 years)
• Overall survival (OS) (From date of randomization to date of death due to any cause, assessed up to 10 years)
• Incidence of adverse events (Up to 10 years)

Full Eligibility Criteria

Inclusion Criteria:

* Participants must have histologically or cytological confirmed diagnosis of clinical stage II-IIIB (excluding clinical N3 disease) non-small cell lung cancer (NSCLC)
* Participants must have had a complete (R0) resection of NSCLC (with appropriate lymph node sampling as defined by the National Comprehensive Cancer Network \[NCCN\] guidelines) within 84 days (12 weeks) prior to randomization. Acceptable types of surgical resection are: lobectomy, sleeve resection, bi-lobectomy, or pneumonectomy. Wedge resection is not allowed.

  * Note the NCCN guidelines: N1 and N2 node resection and mapping is a routine component of lung cancer resections. It is recommended at a minimum one N1 and three N2 stations is sampled or complete lymph node dissection. Formal ipsilateral mediastinal lymph node dissection is indicated for participants undergoing resection for N2 disease
* Participants must have a pathologic complete response (pCR) (no viable tumor in the resected specimen or lymph nodes), as determined by local pathology review
* Participants must have a PD-L1 status result (e.g. \[\< 1% versus \>= 1% or unknown\])
* Participants must not have known EGFR mutations, or ALK gene fusion
* Participants must have received at least two cycles of neoadjuvant platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 therapy. The neoadjuvant treatment must be Food and Drug Administration (FDA) approved and standard of care as listed in NCCN guidelines
* Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for NSCLC treatment while receiving treatment on this study
* Participants must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 28 days prior to randomization
* Participants must not have medical contraindications or severe adverse events to receiving anti-PD-1 or anti-PD-L1 therapy
* Participants must not have received post-operative radiation therapy (PORT) for NSCLC
* Participants must not have any unresolved toxicity National Cancer Institute (NCI) CTCAE grade ≥ 2 from previous anticancer therapy with the exception of alopecia, and vitiligo. Note, participants with grade ≥2 neuropathy may be included at the discretion of the treating investigator. Note, participants with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included at the discretion of the treating investigator
* Participant must be ≥ 18 years old at time of study entry
* Participants must have body weight \> 30 kg
* Participant must have Zubrod performance status of 0-2
* Participant must have a complete medical history and physical exam within 28 days prior to randomization
* Hemoglobin \> 9.0 g/dL (within 28 days prior to randomization)
* Absolute neutrophil count ≥ 1.5 x 10\^3/uL (within 28 days prior to randomization)
* Platelets ≥ 100 x 10\^3/uL (within 28 days prior to randomization)
* Total bilirubin ≤ 1 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 28 days prior to randomization)
* Aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 × institutional ULN (within 28 days prior to randomization)
* Participants must have a calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to randomization. For creatinine clearance formula see the tools on the Clinical Research Associate (CRA) Workbench https://txwb.crab.org/TXWB/Tools.aspx
* Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
* Participants with a known history of human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to randomization
* Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to randomization, if indicated
* Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to randomization, if indicated
* Participants must not have had an organ transplant
* Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* Participant must not have medical contraindications to receiv

Trial Locations

• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro, Jonesboro, Arkansas, United States
• Tower Cancer Research Foundation, Beverly Hills, California, United States
• Veterans Affairs Loma Linda Healthcare System, Loma Linda, California, United States
• Cedars Sinai Medical Center, Los Angeles, California, United States
• University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
• Torrance Memorial Physician Network - Cancer Care, Torrance, California, United States
• Saint Mary's Hospital and Regional Medical Center, Grand Junction, Colorado, United States
• Hartford HealthCare - Avon, Avon, Connecticut, United States
• Hartford Hospital, Hartford, Connecticut, United States
• Hartford HealthCare - Manchester, Manchester, Connecticut, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Non-Small Cell Lung Cancer
• Stage II Lung Cancer
• Stage IIIA Lung Cancer
• Stage IIIB Lung Cancer
• Adjuvant Therapy
• Immunotherapy
• Neoadjuvant Chemotherapy
• Cancer Recurrence
• Thoracic Oncology

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