Durvalumab + SBRT for Non-Small Cell Lung Cancer

(358 Trial)

Not currently recruiting at 1 trial location

Overseen By Roxanne Wood, BA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hina Khan

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Metastatic disease, Severe comorbidity, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for individuals with stage 3 non-small cell lung cancer. It combines Durvalumab, a drug that aids the immune system in fighting cancer, with a focused radiation therapy called SBRT (Stereotactic Body Radiation Therapy). The trial aims to determine if this combination is more effective at attacking cancer cells than the drug alone. Individuals who have completed standard chemotherapy and radiation but still have some remaining tumor may be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to adjust or stop these before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that the combination of Durvalumab and SBRT is likely to be safe?

Research shows that durvalumab is generally well-tolerated. In studies with patients who have non-small cell lung cancer, durvalumab has demonstrated a manageable safety profile. Fatigue and nausea are the most common side effects, but these are usually mild. Serious side effects occur less frequently.

The FDA has already approved durvalumab for treating lung cancer, indicating its safety for this use. The combination of durvalumab with stereotactic body radiation therapy (SBRT) is new. SBRT delivers high doses of radiation directly to the tumor, minimizing harm to healthy lung tissue.

While researchers continue to study the combination of durvalumab and SBRT, each treatment alone has a good safety record. The current study aims to determine their safety and effectiveness when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for non-small cell lung cancer, which often involve chemotherapy and standard radiation, the combination of Durvalumab and SBRT introduces a new approach by harnessing the power of immunotherapy and precise radiation targeting. Durvalumab is an immunotherapy drug that works by blocking a protein called PD-L1, helping the body's immune system identify and attack cancer cells more effectively. This combination with SBRT, a highly targeted form of radiation therapy, allows for precise damage to the tumor while sparing surrounding healthy tissue. Researchers are excited about this treatment because it has the potential to enhance the body's natural defenses against cancer while reducing the side effects typically associated with broader radiation and chemotherapy treatments.

What evidence suggests that the combination of Durvalumab and SBRT could be effective for non-small cell lung cancer?

Studies have shown that Durvalumab can help patients with stage III non-small-cell lung cancer (NSCLC) live longer by aiding the immune system in fighting cancer. Research suggests that Durvalumab might work even better when cancer cells are damaged by stereotactic body radiation therapy (SBRT). SBRT, already used to treat early-stage lung cancer, targets tumors while protecting healthy tissue. In this trial, participants will receive a combination of Durvalumab and SBRT. Although still under study, early results suggest this combination could enhance treatment effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Hina Khan, MD

Principal Investigator

Brown University Oncology Research Group (BrUOG) & Lifespan Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Stage III Non-Small Cell Lung Cancer who've completed chemoradiation but haven't progressed. They must have finished treatment within 3-7 weeks, have a tumor under 120cc suitable for SBRT, and meet certain blood and organ function criteria. Participants need to agree to use contraception and not be pregnant.

Inclusion Criteria

Your blood has enough white blood cells and platelets before joining the study.

Minimum life expectancy of 12 weeks as determined by treating physician

I agree to use effective birth control during and for 6 months after treatment.

Exclusion Criteria

My condition worsened despite receiving chemoradiation.

I had surgery to remove lung cancer but not all of it was taken out.

You currently have active Hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants undergo chemoradiation as part of the initial treatment phase

3-7 weeks

SBRT and Durvalumab Treatment

Participants receive SBRT and Durvalumab, with SBRT delivered over 1-2 weeks and Durvalumab administered every 2 weeks for up to 12 months

12 months

Bi-weekly visits for Durvalumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 1 year, then every 4 months for 2 years, then every 6 months for 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Stereotactic Body Radiation Therapy (SBRT)

Trial Overview The study tests combining Durvalumab, an immune system-stimulating drug approved for lung cancer, with SBRT—a high-dose radiation therapy focused on the tumor. This combination is investigational in stage III patients to see if it's more effective post-chemoradiation.

How Is the Trial Designed?

Group I: Durvalumab and SBRT Experimental Treatment 2 Interventions

Durvalumab 10mg/kg x 1 day, dose #1 to occur \> 3 weeks and \<7 weeks after last chemo/RT and prior to SBRT dose 1 (5-10 day time frame between Durvalumab and SBRT). SBRT boost will consist of 2 fractions delivered to the primary tumor only, over 1-2 weeks between the first and second treatments with durvalumab (see above for time frames). The dose will consist of 20Gy (2 fractions of 10Gy). 3 fractions are allowed for centrally located tumors Dose # 2 of durvalumab, (post SBRT) to be given 1-10 days post last SBRT. Durvalumab then to be given at 10mg/kg Q2 weeks (+/- 4 days) for a total of 12 months (maximum of 26 treatments total)

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?

Hina Khan

Lead Sponsor

Trials

1

Recruited

10+

Brown University

Lead Sponsor

Trials

480

Recruited

724,000+

Lifespan

Collaborator

Trials

43

Recruited

41,100+

Published Research Related to This Trial

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 81 patients with unresectable locally advanced non-small cell lung cancer (NSCLC), those with high tumor mutational burden (TMB-high) showed significantly better outcomes, including lower local-regional failure rates (9% vs 51%) and improved progression-free survival (66% vs 27%) compared to TMB-low patients.

The study suggests that TMB status could be a valuable biomarker for personalizing treatment strategies, as it was the only factor significantly associated with local-regional failure and progression-free survival after treatment with chemoradiation and adjuvant durvalumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Tumor Mutational Burden, Progression-Free Survival, and Local-Regional Control in Patents with Locally Advanced Non-Small Cell Lung Cancer Treated With Chemoradiation and Durvalumab. Lebow, ES., Shepherd, A., Eichholz, JE., et al.[2023]

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 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 the phase III PACIFIC trial, durvalumab significantly improved overall survival (OS) and progression-free survival (PFS) in patients with unresectable stage III non-small-cell lung cancer after chemoradiotherapy, with a 5-year OS rate of 42.9% compared to 33.4% for placebo.

The updated analyses, with a median follow-up of 34.2 months, showed that durvalumab continues to provide durable benefits, establishing a new standard of care for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. Spigel, DR., Faivre-Finn, C., Gray, JE., 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]

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

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03833154

Study Details | NCT03833154 | Durvalumab With ... The primary objective of main cohort is to assess the efficacy of Durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS. Key secondary is ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6831969/

Durvalumab for stage III non-small-cell lung cancer patients A recently published phase III trial (PACIFIC) showed for the first time an improved overall survival in stage III NSCLC patients with consolidative durvalumab.

5. withpower.com withpower.com/trial/phase-3-carcinoma-non-small-cell-lung-4-2019-8eded

Durvalumab + SBRT for Non-Small Cell Lung Cancer It is possible that when cancer cells are damaged by SBRT Durvalumab may be more effective in activating the immune system. SBRT is a standard FDA approved ...

6. dovepress.com dovepress.com/article/download/39200

Safety and efficacy of durvalumab (MEDI4736) in various ... Safety and clinical activity of durvalumab (MEDI4736), an anti-PD-LI antibody, in treatment-naive patients with advanced non-small-cell lung cancer. J Clin ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1525730425001500

Rationale and Design of the AUSTRAL trial: An Open- ... The AUSTRAL trial investigates whether combining thoracic re-irradiation (with optional metastasis-directed SBRT) with durvalumab and ...