Durvalumab for Lung Cancer

Recruiting at 45 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Platinum-based chemotherapy, Anti-PD-1/PD-L1

Must not be taking: Immunosuppressive drugs, Corticosteroids

Disqualifiers: EGFR mutations, ALK gene fusion, Organ transplant, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 12

Duration: 12 months

306 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot receive any other chemotherapy, immunotherapy, or biologic treatments for lung cancer while in the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Durvalumab for lung cancer?

Research shows that Durvalumab, a drug that helps the immune system fight cancer, improves the time patients live without the disease getting worse and increases overall survival in people with stage III non-small cell lung cancer who have already had chemotherapy and radiation. ^{1 2 3 4 5}

What safety data exists for Durvalumab in humans?

Durvalumab, used for treating lung cancer, has been linked to serious side effects like pneumonitis (lung inflammation), myocarditis (heart inflammation), and liver injury. These side effects can be severe and sometimes fatal, so it's important to monitor patients closely during treatment. ^{6 7 8 9 10}

How is the drug Durvalumab unique for treating lung cancer?

Durvalumab is unique because it is an immune checkpoint inhibitor that targets PD-L1, a protein that helps cancer cells evade the immune system. It is specifically used as a consolidation therapy after chemoradiation in stage III non-small cell lung cancer (NSCLC), making it a standard of care for patients with this condition. ^{5 9 11 12 13}

Research Team

Jeremy P Cetnar

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for people who've had surgery for early-stage non-small cell lung cancer and show no remaining cancer cells. They must have followed specific guidelines for lymph node removal, not have certain gene mutations, received approved neoadjuvant therapy, and can't be on other treatments or have had severe reactions to immunotherapy.

Inclusion Criteria

I haven't had chemotherapy, immunotherapy, or experimental drugs in the last 28 days.

My cancer does not have EGFR mutations or ALK gene fusion.

My cancer's PD-L1 status is known.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab intravenously 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.

12 months

12 visits (in-person)

Active Surveillance

Participants undergo active surveillance with CT and blood sample collection throughout the trial.

12 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with annual follow-ups until 10 years from randomization.

Up to 10 years

Treatment Details

Interventions

• Durvalumab

Trial Overview The INSIGHT Trial is testing durvalumab (an immunotherapy drug) against the usual post-surgery observation in patients with early-stage non-small cell lung cancer. It aims to see if durvalumab can help patients live longer and prevent cancer recurrence better than just monitoring.

Participant Groups

Group I: Arm I (durvalumab) Experimental Treatment 4 Interventions

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.

Group II: Arm II (active surveillance) Active Control 4 Interventions

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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

Durvalumab, a PD-L1 inhibitor, has shown promising results in increasing progression-free survival and objective response rates in patients with inoperable and locally advanced stage III non-small cell lung cancer, based on interim results from a phase III trial.

The significant benefits observed suggest that durvalumab could potentially become the standard treatment for these patients in the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Promising for NSCLC. [2019]

In a phase 3 trial involving 713 patients with stage III unresectable non-small-cell lung cancer, durvalumab significantly improved overall survival compared to placebo, with a 24-month survival rate of 66.3% versus 55.6%.

Durvalumab also prolonged progression-free survival, with a median duration of 17.2 months compared to 5.6 months for placebo, and no new safety concerns were identified, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. Antonia, SJ., Villegas, A., Daniel, D., et al.[2022]

In a study of 1006 patients with stage III non-small cell lung cancer (NSCLC), early discontinuation of adjuvant durvalumab therapy was common, primarily due to tumor progression and immune-related adverse events, highlighting the need for careful monitoring during treatment.

The analysis indicated that shorter durations of durvalumab (6 or 9 months) may provide similar progression-free survival compared to the full 12-month course, suggesting that optimizing treatment duration could balance efficacy and patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-escalating adjuvant durvalumab treatment duration in stage III non-small cell lung cancer. Bryant, AK., Sankar, K., Zhao, L., et al.[2023]

In a study of 121 patients with stage III non-small cell lung cancer treated with durvalumab, those with over 50% PD-L1 expression had significantly better outcomes, with a 1-year survival rate of 97% compared to 73% and 78% for lower expression groups.

Higher PD-L1 expression (>50%) was strongly associated with improved progression-free survival and overall survival, indicating that PD-L1 levels could be a key factor in predicting the effectiveness of durvalumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. Jazieh, K., Gad, M., Saad, A., et al.[2022]

In a randomized phase II trial involving 60 patients with resectable non-small cell lung cancer, the addition of sub-ablative radiation to neoadjuvant durvalumab did not increase mortality or major complications compared to durvalumab alone, indicating a safe combination treatment approach.

Both treatment groups experienced similar rates of grade 3/4 adverse events (38% each), with anemia and hypotension being the most common, suggesting that the safety profile of durvalumab remains consistent regardless of the addition of radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non-small cell lung cancer: Results from a randomized trial. Lee, B., Mynard, N., Nasar, A., et al.[2022]

In a study of 112 patients receiving durvalumab for cancer treatment, 19% experienced liver injury, which was linked to higher rates of tumor progression and mortality, indicating that liver injury may be a significant concern in this patient population.

Among the liver injury cases, 29% were classified as probable drug-induced liver injury (DILI) related to durvalumab, but these cases were generally mild and self-limited, suggesting that while monitoring for liver injury is important, severe complications are rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. Swanson, LA., Kassab, I., Tsung, I., et al.[2023]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., et al.[2022]

A 67-year-old male with lung squamous cell carcinoma developed myocarditis after receiving durvalumab, a PD-L1 inhibitor, highlighting the potential for serious cardiac side effects from this treatment.

The patient's myocarditis led to a significant decrease in heart function but improved rapidly with glucocorticoid therapy, suggesting that timely intervention can effectively manage this rare but severe adverse event.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma. Zhou, B., Li, M., Chen, T., et al.[2022]

In a phase 2 trial involving 444 patients with advanced non-small-cell lung cancer (NSCLC), durvalumab (an anti-PD-L1 treatment) showed a response rate of 30.9% in patients with ≥90% PD-L1 expression, indicating its potential efficacy in heavily pretreated cases.

The safety profile of durvalumab was consistent with other similar treatments, with 9% of patients experiencing grade 3 or 4 treatment-related adverse events, suggesting it is manageable and generally safe for use in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. Garassino, MC., Cho, BC., Kim, JH., et al.[2022]

Durvalumab, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

In a study of 323 patients with stage III unresectable non-small cell lung cancer (NSCLC) treated with durvalumab after chemo-radiotherapy, the overall survival was promising at a median of 47 months, but progression-free survival (PFS) varied significantly based on specific genomic alterations.

Patients with KRAS mutations showed better PFS (not reached) compared to those with EGFR or BRAF mutations, indicating that durvalumab may be less effective for certain driver genomic alterations, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations. Riudavets, M., Auclin, E., Mosteiro, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Durvalumab Promising for NSCLC. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. [2022]

3. England pubmed.ncbi.nlm.nih.gov

De-escalating adjuvant durvalumab treatment duration in stage III non-small cell lung cancer. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study. [2023]

5. China pubmed.ncbi.nlm.nih.gov

Tumor PD-L1 expression is associated with outcomes in stage III non-small cell lung cancer (NSCLC) patients treated with consolidation durvalumab. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

SAKK 19/17: safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced nonsmall cell lung cancer and a performance status of 2. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non-small cell lung cancer: Results from a randomized trial. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Liver injury during durvalumab-based immunotherapy is associated with poorer patient survival: A retrospective analysis. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Acute Myocarditis Due to PD-L1 Inhibitor Durvalumab Monotherapy in a Patient With Lung Squamous Cell Carcinoma. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): an open-label, single-arm, phase 2 study. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Durvalumab consolidation in patients with unresectable stage III non-small cell lung cancer with driver genomic alterations. [2022]