Durvalumab + SABR for Non-Small Cell Lung Cancer

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Immunosuppressants, PD1 inhibitors

Disqualifiers: Metastatic NSCLC, Autoimmune diseases, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding an experimental drug, durvalumab (MEDI 4736), to a precise radiation therapy called SABR can more effectively treat non-small cell lung cancer. Researchers aim to determine if this combination can safely reduce cancer growth and improve patients' lives compared to radiation alone. This study is suitable for individuals newly diagnosed with non-small cell lung cancer that hasn't spread and who cannot or choose not to undergo surgery. Participants will be monitored closely to assess how the treatment affects their health over time. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering patients a chance to contribute to 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. 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.

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

Research shows that combining durvalumab with a type of targeted radiation therapy called SABR is generally well-tolerated by patients with non-small cell lung cancer. Some studies have found this combination to be safe. In one study, patients who received both durvalumab and SABR did not experience severe side effects, indicating the treatment was manageable. Another study found that using durvalumab with SABR and chemotherapy was effective and tolerable for patients with certain lung cancers.

Overall, these findings suggest that the treatment might be safe, but individual reactions can vary. It's important to discuss with a healthcare provider whether joining a trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Durvalumab and SABR for treating non-small cell lung cancer because it offers a novel approach compared to traditional treatments like chemotherapy and surgery. Durvalumab is an immunotherapy drug that helps the body's immune system target and destroy cancer cells, unlike chemotherapy, which attacks all rapidly dividing cells. This combination with SABR, a highly precise form of radiation therapy, could potentially enhance the effectiveness of treatment by simultaneously boosting the immune response and directly targeting tumors. This dual-action strategy might lead to improved outcomes and fewer side effects compared to standard treatments.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will compare the combination of durvalumab, a type of immunotherapy, with Stereotactic Ablative Body Radiotherapy (SABR) to radiotherapy alone for treating non-small cell lung cancer. Research has shown that combining durvalumab with SABR may slow the growth of lung tumors. Durvalumab enhances the immune system's ability to find and destroy cancer cells. Early results indicate that this combination is effective and manageable for patients, causing minimal side effects. This makes it a promising option for improving both survival and quality of life for people with lung cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

Ann Raldow, MD

Principal Investigator

Associate Professor

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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]

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 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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04786093

Durvalumab and Stereotactic Radiotherapy for Advanced ... This is a randomized Phase II study which is designed to determine the impact of stereotactic radiotherapy and durvalumab on quality-of-life and oncologic ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41005623/

Durvalumab combined with chemotherapy and Stereotactic ... Conclusions: In oligometastatic NSCLC, the combination of durvalumab, chemotherapy and SABR was effective and tolerable. Patients who did not ...

3. withpower.com withpower.com/trial/phase-2-carcinoma-non-small-cell-lung-9-2017-53d5d

Durvalumab + SABR for Non-Small Cell Lung Cancer This study uses durvalumab (MEDI 4736), an experimental type of drug made by Astra Zeneca Pharmaceuticals, (limited partnership) LP, which in early studies ...

4. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT03148327

Randomized Phase I/II Study of Stereotactic Body Radiotherapy This study uses durvalumab (MEDI 4736), an experimental type of drug made by Astra Zeneca Pharmaceuticals, (limited partnership) LP, which in early studies ...

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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03148327

Randomized Phase I/II Study of Stereotactic Body ... This study uses durvalumab (MEDI 4736), an experimental type of drug made by Astra Zeneca Pharmaceuticals, (limited partnership) LP, which in early studies ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37023987/

Safety and Efficacy Results From iSABR, a Phase 1 Study ... A Phase 1 Study of Stereotactic ABlative Radiotherapy in Combination With Durvalumab for Early-Stage Medically Inoperable Non-Small Cell Lung Cancer