Durvalumab + Chemoradiation for Non-Small Cell Lung Cancer

Not currently recruiting at 992 trial locations

Overseen By Deepti Behl

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunostimulatory agents

Disqualifiers: Autoimmune disease, Hepatitis, Tuberculosis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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 the effectiveness of combining durvalumab with chemotherapy and radiation for individuals with stage III non-small cell lung cancer that cannot be surgically removed. Durvalumab, an immunotherapy drug, aids the immune system in fighting cancer. The study examines whether adding durvalumab before and after chemoradiation extends life or prevents cancer recurrence more effectively than adding it only afterward. Suitable participants include those with stage IIIA/B/C non-small cell lung cancer that cannot be surgically removed or those who have experienced nodal recurrence after surgery for early-stage lung cancer. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that you should not have received chemotherapy or radiotherapy within 4 weeks prior to registration, and you must not be on systemic immunosuppressive medications within 7 days prior to registration. 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 has shown that durvalumab is generally well-tolerated by patients with non-small cell lung cancer (NSCLC). One study found that when used after chemotherapy and radiation, most side effects were mild and manageable with proper care.

Another study involving many patients with advanced lung cancer reported that most experienced mild to moderate side effects, such as tiredness and cough, while serious side effects were less common.

The chemotherapy drugs used in this trial have a long history in cancer treatment, so their side effects are well-known. Common side effects include nausea, hair loss, and low blood cell counts, but these can usually be managed with supportive care.

Overall, evidence suggests that durvalumab, combined with chemotherapy and radiation, is reasonably safe for treating NSCLC. However, like any treatment, it can have side effects, and patients should discuss these with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for non-small cell lung cancer?

Researchers are excited about durvalumab for non-small cell lung cancer because it offers a new approach by enhancing the body's immune response to fight the cancer. While traditional treatments often rely on chemotherapy and radiation alone, durvalumab is a type of immunotherapy that works by blocking the PD-L1 protein, which helps cancer cells evade the immune system. This can potentially increase the effectiveness of existing treatments like chemoradiation. Additionally, when used alongside chemotherapy and radiation, durvalumab may improve patient outcomes by reducing the risk of cancer progression.

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

In this trial, participants will receive either durvalumab combined with chemoradiation or chemoradiation followed by durvalumab. A previous study with patients who have stage III non-small cell lung cancer that cannot be surgically removed showed promising results when durvalumab was added to chemoradiation. Specifically, research indicates that the time during which the cancer did not worsen extended by 11 months with durvalumab. Another study found that after one year, 72.1% of patients' cancer had not progressed, meaning many patients experienced no worsening of cancer for at least a year. These findings suggest that durvalumab, when combined with chemoradiation, may control the cancer more effectively than chemoradiation alone. ^{2 5 6 7 8}

Who Is on the Research Team?

Nathan A Pennell

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

Adults with stage IIIA/B/C non-small cell lung cancer that can't be surgically removed, or those with nodal recurrence after early-stage surgery. Participants must not have lost more than 10% of their weight unintentionally in the last month, should use effective contraception, and have no severe allergies to antibodies or history of certain infections.

Inclusion Criteria

My early-stage lung cancer returned in the lymph nodes after surgery.

My side effects from previous cancer treatments have mostly improved within 45 days, except for hair loss or skin color changes.

You have a measurable disease according to specific guidelines within 4 weeks before signing up for the trial.

Exclusion Criteria

I haven't taken certain medications recently.

I do not have severe lung inflammation.

I have not had a bone marrow or organ transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Concurrent Therapy

Patients receive durvalumab and chemotherapy with radiation therapy for 6 weeks

6 weeks

Weekly visits for radiation therapy

Consolidation Therapy

Patients receive durvalumab every 28 days for 12 cycles

12 months

Monthly visits for durvalumab infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for 2 years, then every 6 months for 3 years, then yearly

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab

Trial Overview The trial is testing if adding durvalumab (an antibody) to standard chemoradiation therapy and continuing it for a year improves outcomes compared to just chemoradiation followed by durvalumab. It's a phase III study aiming to see if this combination extends life or prevents cancer return.

How Is the Trial Designed?

Group I: Arm A (durvalumab, chemotherapy, durvalumab) Experimental Treatment 6 Interventions

STEP 1 (CONCURRENT THERAPY): Patients receive durvalumab IV over 60 minutes on days 1 and 15 of cycle 1 and day 1 of cycle 2. Patients also receive 1 of 3 treatment regimens per investigator choice: 1) etoposide IV over 60 minutes on days 1-5 and cisplatin IV over 60 minutes on days 1 and 8 every 28 days for 2 cycles; 2) pemetrexed disodium IV over 60 minutes and cisplatin IV over 60-120 minutes on day 1 every 21 days for 2 cycles; or 3) paclitaxel IV over 60 minutes and carboplatin IV over 30 minutes on day 1 every 7 days for 6 cycles. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of chemotherapy, patients receive radiation therapy 5 days a week for 6 weeks. STEP 2 (CONSOLIDATION THERAPY): Within 14 days after the last dose of radiation (from Step 1), all patients then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm B (chemotherapy, durvalumab) Active Control 6 Interventions

STEP 1 (CONCURRENT THERAPY): Patients receive 1 of 3 investigator's choice treatment regimens and radiation therapy as in Arm A. STEP 2 (CONSOLIDATION THERAPY): Within 14 days after the last dose of radiation (from Step 1), all patients then receive durvalumab IV over 60 minutes on day 1. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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 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, an immunotherapy drug for non-small cell lung cancer (NSCLC), has shown significant activity and acceptable tolerability, especially in patients with at least 25% PD-L1 tumor expression, and has been established as a standard treatment following chemoradiation based on the PACIFIC study results.

While durvalumab is effective in wild-type EGFR and ALK patients, its efficacy is lower in those with EGFR mutations or ALK-positive status, highlighting the need for ongoing research into combination therapies and the management of treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. Mezquita, L., Planchard, D.[2019]

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]

In a Phase II trial involving 74 patients with unresectable, locally advanced non-small cell lung cancer (NSCLC), durvalumab immunotherapy combined with radiotherapy resulted in a promising 12-month progression-free survival (PFS) rate of 72.1%, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with a high objective response rate of 90.9%, although 52.9% of patients experienced severe adverse events (grade 3 or 4), highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. Tachihara, M., Tsujino, K., Ishihara, T., 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 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]

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]

Citations

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

Durvalumab after Chemoradiotherapy in Stage III Non– ... Among patients with locally advanced, unresectable NSCLC, progression-free survival was 11 months longer among patients who received durvalumab ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12345666/

Real-World Outcomes of Chemoradiotherapy in Patients ... The median progression-free survival (PFS) for the total cohort was 1.17 years. The estimated 3- and 5-year PFS rates were 31.1% and 26.3%, ...

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

Durvalumab Plus Concurrent Radiotherapy for Treatment ... The 12-month PFS rate was 72.1% (90% CI, 59.1%-85.1%), and the median PFS was 25.6 months (95% CI, 13.1 months to not estimable) at a median ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00036

The Phase III PACIFIC-2 Study | Journal of Clinical Oncology Overall, 46.6% of patients in the durvalumab arm and 52.3% in the placebo arm received subsequent anticancer therapy following progression, most ...

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28705024/

MEDI 4736 (durvalumab) in non-small cell lung cancer This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423

NCT02087423 | A Global Study to Assess the Effects of ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.9029

Safety and clinical activity of durvalumab (MEDI4736), an ... A Phase 1/2 dose escalation and dose expansion study is ongoing to evaluate the safety and efficacy of durvalumab, a modified human IgG1 mAb ...