Durvalumab + SBRT for Non-Small Cell Lung Cancer

(358 Trial)

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

11 Participants Needed

Trial Summary

What is the purpose of this trial?

Durvalumab is a drug that stimulates the immune system to fight lung cancer. Durvalumab is FDA approved to treat lung cancer. Stereotactic body radiation therapy (SBRT) is a newer radiation treatment that gives fewer, but higher doses of radiation than standard radiation. With SBRT, radiation is focused toward the cancer and away from normal surrounding lung tissue. 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 treatment for early stage (stage 1) lung cancer and is investigational in patients such as yourself with stage 3 lung cancer. The combination of Durvalumab and SBRT is investigational. This study will investigate the effects, good and bad, of the combination of Durvalumab and SBRT.

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.

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

Research shows that Durvalumab, when used after chemoradiotherapy, significantly improves survival rates in patients with stage III non-small-cell lung cancer. It has been effective in increasing both overall survival and progression-free survival, making it a promising option for treating this type of cancer. ^{1 2 3 4 5}

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

Durvalumab, also known as Imfinzi or MEDI4736, has been shown to have a manageable safety profile in treating various solid tumors, including non-small cell lung cancer. Studies like the PACIFIC trial have demonstrated that it is generally safe when used after chemoradiotherapy, with side effects that are considered manageable. ^{1 2 3 5 6}

How is the drug Durvalumab unique in treating non-small cell lung cancer?

Durvalumab is unique because it is an immune checkpoint inhibitor that blocks PD-L1, helping the immune system attack cancer cells, and is particularly effective when used after chemoradiation in patients with locally advanced non-small cell lung cancer, improving disease control and survival. ^{2 3 5 7 8}

Research Team

Hina Khan, MD

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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, 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]

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]

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]

References

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

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. [2022]

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

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

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

8. Switzerland pubmed.ncbi.nlm.nih.gov

Durvalumab Treatment Patterns for Patients with Unresectable Stage III Non-Small Cell Lung Cancer in the Veterans Health Administration (VHA): A Nationwide, Real-World Study. [2023]