Durvalumab + Chemotherapy for Lung Cancer

(MDT-BRIDGE Trial)

Not currently recruiting at 67 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Disqualifiers: Unresectable NSCLC, Stage IIIC, EGFR mutation, others

Stay on Your Current Meds You can continue your current medications while participating

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: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well the drug durvalumab (Imfinzi) works with chemotherapy for certain types of lung cancer. It aims to determine if this combination is effective and safe for people with specific stages of lung cancer (IIB-IIIB) that can potentially be removed by surgery. Participants will first receive durvalumab and chemotherapy, then either undergo surgery followed by more durvalumab or receive additional treatments. Ideal candidates are those newly diagnosed with specific stages of lung cancer, confirmed by scans and biopsies, who have not yet received treatment and are considered fit for surgery. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that durvalumab combined with chemotherapy is likely to be safe for humans?

Research has shown that durvalumab, the treatment used in this trial, has been tested in various studies and is generally considered safe for patients with different types of solid tumors. When combined with other drugs like tremelimumab, it is usually tolerable, meaning most people can take it without serious problems. One study specifically examined patients with a type of lung cancer similar to the focus of this trial. It found that durvalumab could be safely administered right after other cancer treatments without causing unexpected side effects.

While no treatment is without risks, existing research on durvalumab provides confidence that it is well-tolerated by many patients. Prospective participants can find reassurance in this information, although discussing personal health concerns with a doctor is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Durvalumab is unique because it harnesses the power of the immune system to fight lung cancer. Unlike traditional treatments like chemotherapy that directly attack cancer cells, Durvalumab is an immunotherapy that works by blocking the PD-L1 protein, which often helps cancer cells evade the immune system. By inhibiting this protein, Durvalumab enables the immune system to better recognize and destroy cancer cells. Researchers are excited about this approach because it offers a different way to tackle the disease, potentially leading to more effective and longer-lasting responses in patients.

What evidence suggests that durvalumab combined with chemotherapy might be an effective treatment for lung cancer?

Research has shown that durvalumab, which participants in this trial will receive, helps lung cancer patients live longer when used after combined chemotherapy and radiation. One study found that after 12 months, 83.1% of patients who received durvalumab were still alive, compared to 75.3% of those who did not. Another study found that patients lived longer and their cancer did not worsen as quickly when durvalumab was given soon after treatment. These findings suggest that durvalumab effectively helps patients with non-small cell lung cancer (NSCLC) live longer and slow the progression of their cancer. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Stage IIB-IIIB NSCLC that hasn't been treated yet. They must be able to have surgery, not have certain gene mutations (EGFR/ALK), and agree to use birth control. Pregnant or breastfeeding women, those allergic to the drug being tested, or with other primary tumors can't join.

Inclusion Criteria

My cancer is at Stage IIB to early Stage IIIB.

My cancer is considered operable after team evaluation.

My lymph node status was confirmed with specific imaging and biopsy techniques.

Exclusion Criteria

I cannot have surgery because of other health conditions.

Participants who are allergic to study intervention

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive 2 cycles of neoadjuvant durvalumab and platinum-based chemotherapy every three weeks

6 weeks

2 visits (in-person)

Surgery or Chemoradiotherapy

Participants undergo surgery or receive definitive chemoradiotherapy based on resectability assessment

6 weeks

6 visits (in-person)

Consolidation Treatment

Participants receive durvalumab every four weeks until disease progression or up to one year

up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

3.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab

Trial Overview The study tests Durvalumab combined with chemotherapy before cancer surgery in NSCLC patients. After initial treatment, participants will either go through surgery and more Durvalumab or chemoradiotherapy followed by additional doses of Durvalumab.

How Is the Trial Designed?

Group I: Durvalumab Experimental Treatment 1 Intervention

Durvalumab will be administered to the participants via intravenous infusion (IV)

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

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 phase 3 trial involving 713 patients with stage III unresectable non-small-cell lung cancer, durvalumab significantly improved overall survival compared to placebo, with a 24-month survival rate of 66.3% versus 55.6%.

Durvalumab also prolonged progression-free survival, with a median duration of 17.2 months compared to 5.6 months for placebo, and no new safety concerns were identified, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. Antonia, SJ., Villegas, A., Daniel, D., et al.[2022]

Immune checkpoint inhibitors (ICIs), particularly durvalumab, have significantly improved treatment outcomes for patients with advanced non-small cell lung cancer (NSCLC), establishing them as the standard of care either alone or with chemotherapy.

Durvalumab is specifically approved as a consolidation treatment after chemo-radiotherapy for stage III NSCLC, highlighting its role in enhancing patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. Gullapalli, S., Remon, J., Hendriks, LEL., et al.[2020]

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[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 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]

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 a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7244187/

Three-Year Overall Survival with Durvalumab after ... The 12-, 24- and 36- month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. All secondary ...

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

A phase II study of durvalumab (MEDI4736) immediately ... Progression-free survival (PFS) and overall survival (OS) were better in the subgroup of patients administered durvalumab within 14 days after ...

3. 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 ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809697

Overall Survival with Durvalumab after Chemoradiotherapy ... Efficacy. The 12-month overall survival rate was 83.1% (95% CI, 79.4 to 86.2) in the durvalumab group, as compared with 75.3 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02125461

NCT02125461 | A Global Study to Assess the Effects of ... A global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage III unresectable non-Small Cell lung cancer.

6. 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423?term=AREA%5BBasicSearch%5D(AREA%5BInterventionSearch%5D(DURVALUMAB%20OR%20MEDI4736%20OR%20MEDI-4736%20OR%20Imfinzi))&rank=10

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

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27265743/

A Phase III Study of Durvalumab (MEDI4736) With or ... A global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus ...