Durvalumab + SABR for Non-Small Cell Lung Cancer

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jonsson Comprehensive Cancer Center

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

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

Compensation: Varies

Number of Visits: Unknown

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This study uses durvalumab (MEDI 4736), an experimental type of drug made by Astra Zeneca Pharmaceuticals, (limited partnership) LP, which in early studies has shown to possibly reduce the growth of certain types of lung cancer. The Investigators will enroll up to 105 subjects into the study. After an initial safety sample of 15 individuals receiving durvalumab (MEDI 4736) and Stereotactic Ablative Body Radiotherapy (SABR), if it is shown to be safe to administer this combination of therapies, the next enrolled subjects will be randomized in a 1:1 fashion (each subject with a "50-50 chance" like the flip of a coin) to receive either SABR and durvalumab (MEDI 4736), or SABR alone. Once treatment is completed, all subjects will return to the University of California at Los Angeles (UCLA) for regular follow-up visits to check on their health and outcomes. At visits both prior to and after treatment special blood samples will be drawn to be studied by UCLA scientists to look into the basic science aspects of how durvalumab (MEDI 4736) and radiation work in the body. It is hoped that we will learn more about the basic safety and science of durvalumab (MEDI 4736) combined with Stereotactic Ablative Body Radiotherapy (SABR) vs. SABR alone, while extending the life and quality of life of these subjects.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it does exclude those using immunosuppressive medication within 28 days before starting durvalumab, except for certain low-dose corticosteroids. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Durvalumab + SABR for Non-Small Cell Lung Cancer?

Research shows that using durvalumab after radiotherapy can improve survival in patients with non-small cell lung cancer who can't have chemotherapy. Additionally, combining durvalumab with radiotherapy has shown promise in enhancing the body's immune response against cancer. ^{1 2 3 4 5}

Is the combination of Durvalumab and SABR safe for humans?

Durvalumab, when used after radiotherapy, has been studied for safety in patients with non-small cell lung cancer. Some studies have shown it to be generally safe, but like all treatments, it can have side effects. It's important to discuss potential risks with your healthcare provider. ^{1 5 6 7 8}

How is the treatment with Durvalumab and SABR different for non-small cell lung cancer?

This treatment combines Durvalumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with SABR, a precise form of radiation therapy. This combination is unique because it leverages both the immune system and targeted radiation to potentially improve outcomes for non-small cell lung cancer patients. ^{2 7 9 10 11}

Research Team

Ann Raldow, MD

Principal Investigator

Associate Professor

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed, untreated non-small cell lung cancer that's in stage I. They must be unable to undergo surgery or refuse it and have good organ function and performance status (able to carry out daily activities). Pregnant women, those on immunosuppressants, with certain other health conditions or previous treatments like PD-1/PD-L1 inhibitors are excluded.

Inclusion Criteria

I am older than 18 years.

I am willing and able to follow the study's requirements, including treatments and visits.

Written informed consent obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluation

Exclusion Criteria

I do not have any uncontrolled illnesses.

I have not received a live vaccine within 30 days before joining the study or before getting durvalumab.

I am not pregnant, breastfeeding, or if capable of having children, I am using effective birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Safety Lead-in

Initial safety evaluation of radiation therapy with durvalumab (MEDI 4736) to assess general safety and specific toxicities

4 months

Phase II Treatment

Randomized treatment with either radiation therapy and durvalumab (MEDI 4736) or radiation therapy alone

Up to 5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment with routine CT imaging and clinical evaluations

2 years

Treatment Details

Interventions

• Durvalumab (MEDI 4736)
• Stereotactic Ablative Body Radiotherapy (SABR)

Trial Overview The study tests durvalumab combined with Stereotactic Ablative Body Radiotherapy (SABR) against SABR alone in a randomized fashion. Initially, safety will be assessed in a small group before more participants are randomly assigned to either the combination therapy or just SABR.

Participant Groups

Group I: Regimen A: Phase II Experimental Treatment 2 Interventions

The intervention will be looking at radiotherapy + drug Durvalumab (MEDI 4736)

Group II: Regimen A: Phase I Experimental Treatment 2 Interventions

The intervention will be looking at radiotherapy + drug Durvalumab (MEDI 4736)

Group III: Regimen B: Phase II Active Control 1 Intervention

Radiotherapy alone

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

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

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 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 1006 veterans with stage III non-small cell lung cancer (NSCLC), the addition of durvalumab after chemoradiotherapy significantly improved progression-free survival (PFS) and overall survival (OS), with hazard ratios of 0.62 and 0.57 respectively, indicating a strong benefit from the treatment.

While durvalumab improved OS in veterans compared to those who received only chemoradiotherapy, their survival rates were still lower than those observed in the PACIFIC clinical trial population, suggesting that real-world outcomes may differ from clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Outcomes versus Clinical Trial Results of Durvalumab Maintenance in Veterans with Stage III Non-Small Cell Lung Cancer. Sankar, K., Bryant, AK., Strohbehn, GW., et al.[2022]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

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

Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial. [2021]

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

Real World Outcomes versus Clinical Trial Results of Durvalumab Maintenance in Veterans with Stage III Non-Small Cell Lung Cancer. [2022]

5. England 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A phase 2 trial of durvalumab treatment following radiation monotherapy in patients with non-small cell lung cancer ineligible for stage III chemoradiotherapy: The SPIRAL-RT study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

A phase II study of daily carboplatin plus irradiation followed by durvalumab for stage III non-small cell lung cancer patients with PS 2 up to 74 years old and patients with PS 0 or 1 from 75 years: NEJ039A (trial in progress). [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

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

9. Singapore pubmed.ncbi.nlm.nih.gov

Effect of durvalumab on local control after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer in comparison with chemoradiotherapy alone. [2022]

10. 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]

11. 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]