Durvalumab for Lung Cancer

Recruiting at 180 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether durvalumab, a type of immunotherapy, can prevent early-stage non-small cell lung cancer from returning after surgery. Typically, post-surgery involves monitoring for cancer's return, but this study aims to determine if durvalumab offers a better alternative. Participants must have undergone lung cancer surgery and completed prior chemotherapy and immunotherapy. The study excludes those with certain gene mutations or recent treatments. As a Phase 3 trial, it represents the final step before FDA approval, giving participants an opportunity to contribute to potentially groundbreaking cancer treatment advancements.

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.

Is there any evidence suggesting that durvalumab is likely to be safe for humans?

Research has shown that durvalumab, a treatment under study for lung cancer, is generally safe. In past studies, patients who used durvalumab for up to 12 months mostly tolerated it well. Results from these studies indicate that the drug's benefits outweigh the risks.

While some patients in previous trials experienced side effects, most found them manageable. This suggests that while individual experiences may differ, many can take the treatment without serious issues. Additionally, durvalumab's approval for other conditions suggests it is considered safe.

Overall, evidence supports that durvalumab is well-tolerated, but as with any treatment, individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Durvalumab is unique because it targets the PD-L1 protein, which plays a role in preventing the immune system from attacking cancer cells. Unlike the standard of care for lung cancer, which often includes chemotherapy and radiation, durvalumab is an immunotherapy that helps the immune system recognize and fight cancer cells more effectively. Researchers are excited about durvalumab because it offers a new way to treat lung cancer by potentially boosting the body's natural defenses against tumors, which could lead to longer-lasting responses and fewer side effects compared to traditional treatments.

What evidence suggests that durvalumab might be an effective treatment for early-stage non-small cell lung cancer?

Research shows that durvalumab holds promise for treating non-small cell lung cancer (NSCLC). In earlier studies, patients who took durvalumab after chemotherapy and radiation lived about 11 months longer without cancer progression compared to those who didn’t take the drug. Additionally, long-term studies found that durvalumab improved overall survival. In this trial, some participants will receive durvalumab, while others will undergo active surveillance. Although most research has focused on patients with more advanced NSCLC, these results offer hope for using durvalumab in early-stage disease after surgery. ^{1 4 6 7 8}

Who Is on the Research Team?

Jeremy P Cetnar

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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 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]

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 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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37497677/

Durvalumab real-world treatment patterns and outcomes in ... Durvalumab real-world treatment patterns and outcomes in patients with stage III non-small-cell lung cancer treated in a US community setting.

2. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(25)00154-8/fulltext

Real World Effectiveness of Durvalumab in Stage III ... Although not statistically significant, durvalumab-treated patients with PD-L1 TPS ≥ 1% experienced a modestly greater benefit in OS (2-year OS 74.3% vs. 66.5%) ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01308

Five-Year Survival Outcomes From the PACIFIC Trial These updated analyses demonstrate robust and sustained OS and durable PFS benefit with durvalumab after chemoradiotherapy.

4. jto.org jto.org/article/S1556-0864(25)01014-7/fulltext

Long-Term Safety and Effectiveness of Durvalumab in ... Patients received durvalumab for maximum 12 months and were prospectively followed up for 3 years, including the post-durvalumab treatment ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709937

Durvalumab after Chemoradiotherapy in Stage III Non– ... Among patients with locally advanced, unresectable NSCLC, progression-free survival was 11 months longer among patients who received durvalumab ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00036

The Phase III PACIFIC-2 Study | Journal of Clinical Oncology In the phase III PACIFIC trial, 12 months of consolidation durvalumab had a favorable benefit-risk profile versus placebo among patients with ...

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00494-7/fulltext

A phase II clinical trial evaluating the safety and efficacy of ... This study demonstrates that single agent durvalumab is safe and well tolerated in the 1st line treatment of patients with advanced NSCLC and ECOG PS of 2, with ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9015199/

Five-Year Survival Outcomes From the PACIFIC Trial An estimated 42.9% of patients randomly assigned to durvalumab remain alive at 5 years and 33.1% of patients randomly assigned to durvalumab remain alive and ...