Durvalumab + Radiation for Non-Small Cell Lung Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Durvalumab

Must not be taking: Immunosuppressants, Systemic steroids

Disqualifiers: Autoimmune disease, Active infection, Cardiac issues, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 24 months

11 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and side effects of combining durvalumab, an immunotherapy drug, with grid therapy, a specialized radiation treatment, for non-small cell lung cancer. Durvalumab boosts the immune system to attack cancer, while grid therapy targets radiation to kill tumor cells. The researchers aim to determine if this combination is more effective for patients whose cancer progressed despite previous durvalumab treatment. Suitable candidates have non-small cell lung cancer that worsened during or within six months after receiving durvalumab and have a tumor outside the brain treatable with grid therapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 14 days before starting durvalumab, except for certain low-dose or local steroids. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that durvalumab is usually well-tolerated by patients with non-small cell lung cancer (NSCLC). In earlier studies, many patients experienced mild side effects like tiredness and nausea, while serious side effects were less common. Some patients in other studies encountered more severe issues, such as lung inflammation, but these were rare.

Research has found grid therapy to be safe and effective, with most side effects being mild. One study reported that only a few patients experienced severe side effects, and there were no reports of life-threatening reactions.

Both treatments have shown promise in aiding the body's immune system to fight cancer while keeping side effects manageable for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for non-small cell lung cancer, like chemotherapy and radiation, focus on directly attacking cancer cells. But durvalumab works differently. It’s an immunotherapy that enhances the body’s immune system to recognize and attack cancer cells, functioning as a checkpoint inhibitor. Researchers are excited because this approach could potentially lead to longer-lasting responses and better outcomes compared to traditional treatments. Additionally, combining durvalumab with grid therapy and subsequent palliative radiation might enhance its effectiveness, offering a new hope for patients with this type of lung cancer.

What evidence suggests that durvalumab and grid therapy could be effective for non-small cell lung cancer?

Research has shown that durvalumab can effectively treat non-small cell lung cancer (NSCLC). One study found that patients with stage III NSCLC who received durvalumab lived longer than those who did not. Specifically, those treated with durvalumab after standard chemotherapy and radiation had better five-year survival rates.

Grid therapy, a type of radiation treatment, also shows promise. It targets small areas of the tumor with high doses of radiation, helping to kill cancer cells while protecting nearby healthy tissue. Studies have found that over 90% of patients respond well to this treatment, and about 27% see their tumors completely disappear.

In this trial, participants will receive a combination of durvalumab and grid therapy, which might enhance the treatment's effectiveness for NSCLC. ^{2 3 4 6 7}

Who Is on the Research Team?

Dawn Owen, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults with non-small cell lung cancer who've seen their cancer progress during or within 6 months after the PACIFIC regimen, which includes durvalumab. They must weigh over 30 kg, have proper kidney and liver function, a stable blood count, and no severe psychiatric conditions or substance abuse issues. Pregnant or nursing individuals can't join, nor those unwilling to use contraception. Participants should not have had certain recent treatments or suffer from active infections like hepatitis B/C or tuberculosis.

Inclusion Criteria

I have cancer that has spread to my brain.

Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 2.5 x ULN (=< 5 x ULN for patients with liver involvement) (obtained =< 15 days prior to registration)

My condition worsened while on durvalumab or within 6 months after my last dose.

Exclusion Criteria

I am of childbearing age or can father a child and am not using birth control.

I do not have any serious ongoing illnesses that would affect my participation.

Pregnant persons

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab IV over 60 minutes on day 1 of each cycle, with treatment repeating every 28 days for up to 24 cycles. Patients also undergo grid therapy on day 1 and palliative radiation therapy for 5 fractions beginning 7-14 days after grid therapy.

24 months

Monthly visits for durvalumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits at 30 days and then every 8-12 weeks.

Up to 5 years

Follow-up visits every 8-12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Grid Therapy

Trial Overview The trial is testing the combination of durvalumab (an immunotherapy drug) with grid therapy (a type of radiation that targets small areas of tumors). The goal is to see if this combo helps durvalumab work better in killing tumor cells while sparing normal tissue. Durvalumab aims to boost the immune system's attack on cancer by interfering with tumor growth.

How Is the Trial Designed?

Group I: Treatment (durvalumab, grid therapy) Experimental Treatment 3 Interventions

Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo grid therapy on day 1. Beginning 7-14 days after grid therapy, patients also undergo palliative radiation therapy for 5 fractions. Additionally, patients undergo blood sample collection at baseline and throughout study.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 68 patients with locally advanced non-small cell lung cancer treated with intensity-modulated radiotherapy (IMRT), the administration of durvalumab significantly improved distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), with hazard ratios of 0.31, 0.33, and 0.32 respectively.

The study also found that while grade 2 or higher radiation pneumonitis (RP) was associated with worse DMFS, reducing the incidence of RP could enhance patient outcomes, highlighting the importance of managing treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. Yamamoto, T., Tsukita, Y., Katagiri, Y., et al.[2022]

In the Phase 3 PACIFIC study involving 713 patients with unresectable stage III non-small-cell lung cancer (NSCLC), the anti-PD-L1 agent durvalumab significantly improved median progression-free survival (17.2 months vs. 5.6 months for placebo) and overall survival (not reached vs. 28.7 months for placebo).

While durvalumab showed a slight increase in grade 3 or 4 toxicity (30.5% vs. 26.1% for placebo), its efficacy in prolonging survival justifies its use, leading to its licensing for this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited). Patel, P., Alrifai, D., McDonald, F., et al.[2023]

The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.

This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Filippi, AR., Dziadziuszko, R., García Campelo, MR., et al.[2022]

In a study of 81 patients with unresectable locally advanced non-small cell lung cancer (NSCLC), those with high tumor mutational burden (TMB-high) showed significantly better outcomes, including lower local-regional failure rates (9% vs 51%) and improved progression-free survival (66% vs 27%) compared to TMB-low patients.

The study suggests that TMB status could be a valuable biomarker for personalizing treatment strategies, as it was the only factor significantly associated with local-regional failure and progression-free survival after treatment with chemoradiation and adjuvant durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. Lebow, ES., Shepherd, A., Eichholz, JE., et al.[2023]

This Phase II study (DOLPHIN) is investigating the safety and efficacy of durvalumab combined with radiation therapy in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) who are PD-L1 positive and unable to undergo chemotherapy, aiming for improved outcomes without the adverse effects of chemotherapy.

The primary goal is to evaluate the 12-month progression-free survival rate, with secondary goals including overall survival and safety, highlighting the potential of combining immunotherapy and radiotherapy for better treatment options in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design for a Multicenter, Phase II Study of Durvalumab Plus Concurrent Radiation Therapy in Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Study (WJOG11619L). Tachihara, M., Tsujino, K., Ishihara, T., et al.[2021]

In a study involving 10 patients receiving palliative radiotherapy (RT) combined with durvalumab, the treatment was well tolerated, with only 50% experiencing mild to moderate adverse events, primarily G2 mucositis, and no severe adverse events reported.

The treatment showed promising efficacy, with a 60% objective response rate in evaluable lesions and a significant decrease in tumor growth rate after RT, indicating that durvalumab combined with RT may effectively reduce tumor size in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Levy, A., Massard, C., Soria, JC., et al.[2022]

In the phase III PACIFIC trial, durvalumab significantly improved overall survival (OS) and progression-free survival (PFS) in patients with unresectable stage III non-small-cell lung cancer after chemoradiotherapy, with a 5-year OS rate of 42.9% compared to 33.4% for placebo.

The updated analyses, with a median follow-up of 34.2 months, showed that durvalumab continues to provide durable benefits, establishing a new standard of care for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. Spigel, DR., Faivre-Finn, C., Gray, JE., 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 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 107 patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) and intensity-modulated radiotherapy (IMRT), the median progression-free survival (PFS) was 20.7 months, indicating effective treatment outcomes.

Factors associated with longer PFS included a favorable response to CCRT, a radiation dose of 62 Gy or more, and having stage IIIA NSCLC, while shorter durations of durvalumab treatment and lower radiation doses were linked to increased mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. Takeda, Y., Kusaba, Y., Tsukita, Y., et al.[2022]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

In a Phase II trial involving 74 patients with unresectable, locally advanced non-small cell lung cancer (NSCLC), durvalumab immunotherapy combined with radiotherapy resulted in a promising 12-month progression-free survival (PFS) rate of 72.1%, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with a high objective response rate of 90.9%, although 52.9% of patients experienced severe adverse events (grade 3 or 4), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. Tachihara, M., Tsujino, K., Ishihara, T., et al.[2023]

Citations

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4. imfinzihcp.com imfinzihcp.com/nsclc/stage-3/efficacy.html

IMFINZI® Efficacy for unresectable Stage III NSCLC Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. J Clin Oncol. 2022;40(12): ...

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MEDI 4736 (durvalumab) in non-small cell lung cancer This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials.

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Safety and clinical activity of durvalumab (MEDI4736), an ... A Phase 1/2 dose escalation and dose expansion study is ongoing to evaluate the safety and efficacy of durvalumab, a modified human IgG1 mAb ...