660 Participants Needed

Durvalumab + Chemoradiation for Non-Small Cell Lung Cancer

Recruiting at 966 trial locations
HJ
NA
WP
Dr. Deepti Behl, M.D. | Sutter Health
Overseen ByDeepti Behl
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll 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 DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well an antibody (durvalumab) with chemotherapy and radiation therapy (chemoradiation) works in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This study is being done to see if adding durvalumab to standard chemoradiation followed by additional durvalumab can extend patients life and/or prevent the tumor from coming back compared to the usual approach of chemoradiation alone followed by durvalumab.

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.

What data supports the effectiveness of the drug Durvalumab in treating non-small cell lung cancer?

Research shows that adding Durvalumab to chemoradiation improves disease control and survival in patients with locally advanced non-small cell lung cancer. The PACIFIC trial found that Durvalumab significantly increased overall survival and progression-free survival compared to a placebo, with a manageable safety profile.12345

Is durvalumab safe for humans?

Durvalumab, also known as MEDI4736 or Imfinzi, has shown a manageable safety profile in treating various cancers, including non-small cell lung cancer. It is generally well-tolerated, but treatment-related side effects can occur, especially when combined with other therapies like chemotherapy or radiotherapy.13467

What makes the drug Durvalumab unique for treating non-small cell lung cancer?

Durvalumab is unique because it is used after chemoradiation to improve survival in patients with locally advanced non-small cell lung cancer, and it works by enhancing the immune system's ability to fight cancer cells. This combination of immunotherapy with chemoradiation is a newer approach that has shown better disease control and survival rates compared to traditional treatments.128910

Research Team

NA

Nathan A Pennell

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

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.
See 22 more

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.
See 19 more

Timeline

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

Treatment Details

Interventions

  • Durvalumab
Trial OverviewThe 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.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm A (durvalumab, chemotherapy, durvalumab)Experimental Treatment6 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 Control6 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

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

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.
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.
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.
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors.Yang, H., Shen, K., Zhu, C., et al.[2022]

References

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]
De-escalating adjuvant durvalumab treatment duration in stage III non-small cell lung cancer. [2023]
Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]
Durvalumab in non-small-cell lung cancer patients: current developments. [2018]
Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. [2022]
Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. [2022]
Durvalumab for the treatment of non-small cell lung cancer. [2019]
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. [2022]
Durvalumab Plus Concurrent Radiotherapy for Treatment of Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Phase 2 Nonrandomized Controlled Trial. [2023]
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. [2022]