Durvalumab + Radiation for Lung Cancer

Not currently recruiting at 11 trial locations

Overseen By Charles Simone, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Anti-PD-1, Anti-PD-L1, others

Disqualifiers: Autoimmune disorders, Active infection, Cardiovascular disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining the drug durvalumab (Imfinzi) with stereotactic body radiation therapy (SBRT) is more effective for treating early-stage non-small cell lung cancer (NSCLC) than SBRT alone. It evaluates the effectiveness of this combined treatment compared to standard radiation in shrinking or controlling the cancer. The trial targets individuals with early-stage NSCLC who cannot undergo surgery but can receive SBRT. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medication within 14 days before starting durvalumab, and certain prior therapies have specific washout periods. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medication within 14 days before starting the study drug, except for certain types like inhaled or topical steroids.

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

Research shows that durvalumab is generally well-tolerated, meaning most people can take it without serious problems. Studies have found that it can be safely administered to patients with non-small cell lung cancer (NSCLC) without unexpected side effects, and most patients did not experience severe negative reactions.

Research suggests that stereotactic body radiation therapy (SBRT) is a safe and effective treatment for early-stage NSCLC. Patients often experience fewer short-term side effects compared to surgery. SBRT is a precise type of radiation therapy that targets tumors with high doses while protecting healthy tissue.

Overall, these findings suggest that both durvalumab and SBRT are safe options, making them promising treatments for early-stage NSCLC. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for early-stage non-small cell lung cancer (NSCLC) typically involve surgery, chemotherapy, and traditional radiation therapy. However, the combination of Durvalumab and Stereotactic Body Radiation Therapy (SBRT) offers a unique approach. Durvalumab is an immunotherapy drug that works by blocking the PD-L1 pathway, helping the immune system better recognize and attack cancer cells. SBRT delivers highly focused radiation doses with precision, minimizing damage to surrounding healthy tissue. Researchers are excited about this combination because it has the potential to enhance the body's immune response while precisely targeting tumors, offering a promising option for patients who are ineligible for surgery.

What evidence suggests that durvalumab combined with stereotactic body radiation therapy might be an effective treatment for early-stage non-small cell lung cancer?

Studies have shown that stereotactic body radiation therapy (SBRT) is a safe and effective treatment for early-stage non-small cell lung cancer (NSCLC). It serves as the standard treatment for these cases. In this trial, participants will receive SBRT, and research suggests that adding durvalumab, an immunotherapy, might enhance results further. Early findings indicate that this combination could boost the body's ability to attack cancer cells, potentially leading to better outcomes than using SBRT alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Charles Simone, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with early-stage non-small cell lung cancer who can't or choose not to have surgery. They should be in good physical condition, weigh over 30kg, and have a life expectancy of at least 12 weeks. Patients must not have certain mutations, autoimmune diseases, severe illnesses, or previous treatments that could interfere with the study.

Inclusion Criteria

You weigh more than 30 kilograms.

My lung cancer is in an early stage (I to IIIA) without spread to nearby nodes.

I am fully active or able to carry out light work.

Exclusion Criteria

I have received treatments before.

I have had cancer spread to the lining of my brain and spinal cord.

Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic body radiation therapy (SBRT)

6-8 weeks

Treatment

Participants receive durvalumab in combination with SBRT

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Stereotactic Body Radiation Therapy

Trial Overview The study is testing if combining durvalumab (a drug) with stereotactic body radiation therapy (SBRT) works better than SBRT alone for treating early-stage non-small cell lung cancer. Participants will receive both the drug and radiation to see if this improves their treatment outcomes.

How Is the Trial Designed?

Group I: Participants with Early-stage Non-Small Cell Lung Cancer Experimental Treatment 2 Interventions

Participants will be diagnosed with Stage I-IIIA NSCLC and will be ineligible for surgery and will have any level of PD-L1

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

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]

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 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]

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 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]

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]

Durvalumab has been approved for use in patients with locally advanced PD-L1-positive non-small cell lung cancer (NSCLC) after chemoradiotherapy, based on its efficacy demonstrated in the PACIFIC trial and subsequent analysis of 211 patients in the Expanded Access Program (EAP).

In the EAP, 126 patients who received durvalumab were included, some of whom had oligometastatic disease and a history of autoimmune conditions, indicating that durvalumab may be effective and safe for a broader patient population than previously studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. Faehling, M., Schumann, C., Christopoulos, P., et al.[2020]

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, 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]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

Patients with locally advanced non-small cell lung cancer (LA-NSCLC) who received concurrent chemoradiotherapy (CCRT) and durvalumab had a significantly higher 1-year local control rate (89%) compared to those who received CCRT alone (47%), indicating that adding durvalumab may enhance local tumor control.

While the addition of durvalumab improved local control, it was associated with a slightly higher incidence of grade 2 pneumonitis (50% in the durvalumab cohort vs. 41% in the CCRT-alone cohort), highlighting the importance of monitoring for respiratory side effects in patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Efficacy and Toxicity of Concurrent Chemoradiotherapy and Durvalumab and Concurrent Chemoradiotherapy Alone for Locally Advanced Non-small Cell Lung Cancer With N3 Lymph Node Metastasis. Abe, T., Iino, M., Saito, S., et al.[2023]

In a study of 126 patients with unresectable stage III non-small-cell lung cancer, 56% were eligible for durvalumab after chemoradiotherapy, and those who were ineligible had significantly shorter progression-free survival (9.7 months vs. 18.4 months) and overall survival (26.4 months vs. 58.7 months).

The research indicates that durvalumab is safe and beneficial for a considerable number of patients who do not meet the eligibility criteria of the PACIFIC trial, suggesting that its use could be expanded beyond the trial's limitations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of durvalumab in stage III non-small-cell lung cancer based on eligibility for the PACIFIC study. Boys, E., Gao, B., Hui, R., 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]

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]

Citations

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Study Details | NCT03833154 | Durvalumab With ... This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8107760/

Stereotactic radiotherapy for early stage non-small cell lung ... SBRT has been proven to be a safe, effective and efficient treatment for early stage non-small cell lung cancer (NSCLC) and is presently considered the standard ...

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Durvalumab with stereotactic body radiation therapy (SBRT ... This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus ...

4. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/non-small-cell-lung-cancer

Non-Small Cell Lung Cancer Clinical Trials The purpose of this study is to assess the effectiveness and safety of durvalumab (MEDI4736) and domvanalimab (AB154) compared with durvalumab plus placebo in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04889066

Study Details | NCT04889066 | Durvalumab (MEDI4736) ... This study will look at the combination of the novel immunotherapy Durvalumab with two different ways of delivering SRS: 1) with each radiation treatment given ...

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215TiP A phase II study of durvalumab (MEDI 4736) ... DURVALUNG study aims to evaluate the efficacy of durvalumab maintenance specifically in frail LD-SCLC pts who have not progressed following concomitant or ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28705024/

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.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(DURVALUMAB%20OR%20MEDI4736%20OR%20MEDI-4736%20OR%20Imfinzi))&rank=10

A Global Study to Assess the Effects of MEDI4736 ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

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A phase II study of durvalumab (MEDI4736) immediately ... Durvalumab can be safely administered immediately after completion of CCRT for patients with unresectable stage III NSCLC, no additional or unexpected toxicity ...

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A Phase III Study of Durvalumab (MEDI4736) With or ... A global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus ...