Durvalumab + Radiation for Lung Cancer

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

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether combining the drug durvalumab with a precise radiation treatment is more effective for early-stage lung cancer patients than using the radiation treatment alone. Durvalumab has shown promise in improving survival rates in advanced lung cancer patients and is being tested in various combinations, including with radiation therapy.

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.

What data supports the idea that Durvalumab + Radiation for Lung Cancer is an effective treatment?

The available research shows that using Durvalumab with radiation for lung cancer is effective. In one study, patients with stage III non-small cell lung cancer who received Durvalumab after chemoradiotherapy had a longer time without the cancer spreading and lived longer overall compared to those who did not receive Durvalumab. Specifically, the median time without cancer progression was 17.2 months for those on Durvalumab, compared to 5.6 months for those who received a placebo. Additionally, the overall survival was longer for those on Durvalumab. Although there was slightly more severe side effects in the Durvalumab group, the benefits in survival and disease control were significant. ^{1 2 3 4 5}

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

Research shows that Durvalumab, when used after chemoradiotherapy for stage III non-small cell lung cancer, significantly improves survival rates. Patients treated with Durvalumab had longer progression-free survival and overall survival compared to those who received a placebo. ^{1 2 3 4 5}

What safety data is available for Durvalumab and Radiation in lung cancer treatment?

Safety data for Durvalumab, also known as Imfinzi or MEDI4736, indicates an increased risk of immune-related adverse effects, particularly pneumonitis, as noted in the PACIFIC trial and real-world studies. The German EAP study also documented adverse events in patients treated with Durvalumab after chemoradiotherapy. Additionally, a meta-analysis of Durvalumab in various solid tumors provides further safety insights. Combining Durvalumab with Tremelimumab has shown higher adverse event rates compared to Durvalumab alone. ^{6 7 8 9 10}

Is the combination of Durvalumab and radiation generally safe for humans?

Durvalumab, used in combination with radiation, has been shown to have a manageable safety profile in treating lung cancer, but it can increase the risk of serious side effects like pneumonitis (inflammation of the lungs). It has been tested in various solid tumors and is considered safe enough for use in clinical settings, though patients should be monitored for immune-related side effects. ^{6 7 8 9 11}

Is the treatment Durvalumab with Radiation promising for lung cancer?

Yes, Durvalumab combined with radiation is promising for lung cancer. It has shown to improve survival rates and extend the time patients live without the disease getting worse. This combination works well because radiation and Durvalumab, an immune-boosting drug, enhance each other's effects. ^{1 5 12 13 14}

How is the treatment of Durvalumab + Radiation for Lung Cancer different from other treatments?

This treatment combines durvalumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with stereotactic body radiation therapy (a precise form of radiation), offering a potentially more effective option for patients who cannot undergo standard chemoradiotherapy due to high toxicity. ^{1 5 12 13 14}

Research Team

Charles Simone, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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 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]

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 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, 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]

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 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]

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]

References

1. England 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). [2023]

2. Greece 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. [2023]

3. England 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. [2022]

4. Ireland 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. [2022]

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. Netherlands pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. [2020]

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

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

9. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

10. Switzerland 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. [2023]

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

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

12. Singapore pubmed.ncbi.nlm.nih.gov

Use of durvalumab in stage III non-small-cell lung cancer based on eligibility for the PACIFIC study. [2023]

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

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. [2022]

14. United States 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. [2023]