Durvalumab + Radiation Therapy for Lung Cancer

Not currently recruiting at 11 trial locations

Overseen By Jamie Chaft, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Monoclonal antibodies

Disqualifiers: Autoimmune disorders, Prior thoracic radiation, 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 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining durvalumab, a type of immunotherapy, with radiation can slow the progression of non-small cell lung cancer. It focuses on patients who typically receive chemotherapy followed by radiation but are trying this new combination instead. The trial targets those with locally-advanced lung cancer (stage II-III) who cannot undergo surgery or chemotherapy due to medical reasons. Participants will receive durvalumab alongside radiation and then continue with durvalumab for up to a year. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 7 days before starting the trial, except for certain types like inhaled or topical steroids. It's best to discuss your specific medications with the study team.

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

Research has shown that using durvalumab with radiation therapy for non-small cell lung cancer is generally well-tolerated. One study found that this combination produced promising results with manageable side effects. Most patients completed the treatment without major issues.

Some patients experienced side effects, which is common in cancer treatments. These included fatigue, skin reactions, and some lung inflammation. However, for most, these side effects were not severe.

Durvalumab is already approved for use in other cancer treatments, indicating it has been tested for safety. Past studies have demonstrated that combining it with radiation therapy is both effective and tolerable. This provides reassurance about its safety for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining durvalumab with radiation therapy for non-small cell lung cancer because it offers a fresh approach to treatment. Unlike traditional therapies that might rely solely on chemotherapy, durvalumab is an immunotherapy that helps the immune system recognize and attack cancer cells. By using durvalumab concurrently with radiation, there's potential for a synergistic effect, where the radiation helps expose more cancer cells for the immune system to target. This approach might enhance the overall effectiveness of treatment and offer new hope for patients with locally-advanced stages of this cancer.

What evidence suggests that Durvalumab and radiation therapy might be an effective treatment for non-small cell lung cancer?

Research has shown that durvalumab can extend the lives of people with non-small cell lung cancer (NSCLC) when used after chemotherapy and radiation. In studies, patients who received durvalumab lived longer than those who did not. Specifically, after five years, those treated with durvalumab had better survival rates. Radiation therapy also improves outcomes for lung cancer patients. In this trial, all participants with locally-advanced NSCLC will receive durvalumab concurrently with thoracic radiation. The study examines how combining these treatments might slow the disease and improve overall survival chances. ^{5 6 7 8 9}

Who Is on the Research Team?

Narek Shaverdian, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed or recurrent stage II-III non-small cell lung cancer (NSCLC) who can't have surgery and aren't fit for chemotherapy. They should expect to live at least 12 weeks, be able to consent, and meet certain health criteria like proper organ function. Pregnant women, those on recent immunosuppressants, or with other active cancers can't join.

Inclusion Criteria

I can take care of myself and perform daily activities.

Female participants must either be past menopause or have a negative pregnancy test if they are still having periods.

My lung cancer type has been confirmed by a standard biopsy.

Exclusion Criteria

I have a lung or esophagus condition that needs treatment.

I cannot undergo radiotherapy due to health reasons.

I have another cancer that is getting worse or needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab concurrently with thoracic radiation therapy

6 weeks

Weekly visits (in-person)

Maintenance

Durvalumab is continued up to 1 year as maintenance or until disease progression or unacceptable toxicity

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Radiation Therapy

Trial Overview The study tests if combining Durvalumab (an immune therapy drug) with radiation therapy delays NSCLC progression compared to the usual treatment sequence of chemo followed by radiation. Participants will receive both Durvalumab and targeted radiation treatments.

How Is the Trial Designed?

Group I: Non-Small Cell Lung Cancer Experimental Treatment 2 Interventions

All participants have locally-advanced non-small cell lung cancer, Stage II-III. Treatment will consist of durvalumab administered concurrently with thoracic radiation consisting of 60 Gy in 30 fractions. Patients will be monitored weekly during on-treatment visits. Durvalumab will then be continued up to 1 year as maintenance or until disease progression or unacceptable toxicity. Optional Research MRIs (Does not apply to the Alliance Sites. Research MRIs will only be done at MSKCC)

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+

Published Research Related to This Trial

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 56 patients with non-small cell lung cancer (NSCLC), those treated with intensity-modulated radiation therapy (IMRT) had a significantly lower incidence of grade 2 or higher radiation pneumonitis (RP) compared to those treated with three-dimensional conformal radiotherapy (3D-CRT), with rates of 27.0% versus 64.0%.

The study identified that the radiation technique (IMRT vs. 3D-CRT) and the volume of lung receiving radiation (V20) were significant risk factors for developing RP, suggesting that IMRT may be a safer option for reducing RP in NSCLC patients undergoing concurrent chemoradiotherapy followed by durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the incidence of ≥ grade 2 radiation pneumonitis between intensity-modulated radiotherapy and three-dimensional conformal radiotherapy in patients with unresectable non-small cell lung cancer treated with durvalumab after concurrent chemoradiotherapy. Masuo, M., Shinohara, E., Kitano, M., 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]

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]

In the phase III PACIFIC trial, durvalumab treatment led to a low incidence of immune-mediated adverse events (imAEs), with any-grade immune-mediated pneumonitis occurring in 9.4% of patients and grade 3/4 imAEs in only 3.4%.

Despite the occurrence of imAEs being more common with durvalumab compared to placebo, these events were generally manageable with treatments like corticosteroids, indicating that the benefits of the PACIFIC regimen outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Naidoo, J., Vansteenkiste, JF., Faivre-Finn, C., 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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709937

Durvalumab after Chemoradiotherapy in Stage III Non– ... This phase 3 study compared the anti–programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC

2. 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): ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... 57. A clinical trial of durvalumab (MEDI4736) as 1st line therapy in advanced non-small cell lung cancer patients. [Accessed June 16, 2018] ...

4. esmoopen.com esmoopen.com/article/S2059-7029(24)00556-8/fulltext

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 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.8536

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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37676681/

Durvalumab Plus Concurrent Radiotherapy for Treatment ... Objective: To investigate the efficacy and safety of durvalumab immunotherapy plus concurrent radiotherapy followed by maintenance with ...

7. esmoopen.com esmoopen.com/article/S2059-7029(25)01429-2/fulltext

the DUART phase II nonrandomized controlled study In the phase III, placebo-controlled PACIFIC study (NCT02125461), durvalumab significantly improved progression-free survival (PFS) and overall ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04003246

Phase II Concurrent Durvalumab and Radiotherapy for ... To determine the 12-month progression-free survival (PFS) for Stage III non-small cell lung cancer patients treated with concurrent durvalumab and radiotherapy ...

9. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2809271

Durvalumab Plus Concurrent Radiotherapy for Treatment ... Findings suggest that durvalumab plus concurrent radiotherapy for treatment of unresectable, locally advanced NSCLC showed promising efficacy with tolerable ...