Chemotherapy + Durvalumab for Lung Cancer

Not currently recruiting at 17 trial locations

Overseen By Quality Management and Compliance

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance Foundation Trials, LLC.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Prior NSCLC treatment, 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

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of chemotherapy and durvalumab (an immunotherapy) to treat certain types of lung cancer. The goal is to determine if this approach improves the chances of clearing cancer from the lymph nodes compared to chemotherapy alone. It targets individuals with specific types of lung cancer (stage IIIA/B NSCLC) who might be candidates for surgery. Suitable participants should have lung cancer that is potentially removable by surgery and no major health issues that would make surgery risky. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering a chance to contribute to important advancements in lung cancer treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroids or immunosuppressive medications, you may need to stop them 14 days before starting the study drug. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using durvalumab with chemotherapy is generally safe for people with lung cancer. One study found that patients receiving durvalumab after other cancer treatments did not experience unexpected side effects. Patients did not face new or severe health issues beyond what doctors anticipated.

Platinum doublet chemotherapy, a common treatment for lung cancer, is usually well-tolerated. Expected side effects include nausea, tiredness, and changes in blood cell counts. These side effects are typical for many chemotherapy treatments and can usually be managed with medical care.

Overall, studies have indicated that the combination of durvalumab and platinum chemotherapy is safe for patients with lung cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Unlike the standard treatments for lung cancer, which often rely solely on chemotherapy or surgery, the combination of Durvalumab with platinum doublet chemotherapy brings a fresh approach. Durvalumab is an immunotherapy drug that works by boosting the body's immune response against cancer cells, potentially leading to better outcomes. This combined treatment strategy not only aims to shrink tumors before surgery but also continues to target any remaining cancer cells afterward, offering a more comprehensive attack on the disease. Researchers are particularly excited about Durvalumab's potential to enhance the effectiveness of chemotherapy and improve long-term survival rates.

What evidence suggests that this treatment might be an effective treatment for lung cancer?

Research shows that combining durvalumab with chemotherapy holds promise for treating lung cancer. In this trial, participants will receive a neoadjuvant treatment of platinum doublet chemotherapy plus durvalumab, followed by surgery, postoperative radiation, and adjuvant durvalumab for 13 cycles. Studies have found that using durvalumab after standard chemoradiotherapy can significantly increase survival rates for patients with stage III non-small cell lung cancer (NSCLC). Another study found that durvalumab can be safely given with chemotherapy without causing unexpected side effects. The current research aims to improve the removal of cancer from lymph nodes (known as N2 nodal clearance) from 30% to 50% or more, which could greatly enhance treatment outcomes. These findings suggest that adding durvalumab to chemotherapy might make lung cancer treatment more effective. ^{1 2 3 6 7}

Who Is on the Research Team?

Evanthia Galanis, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Linda Martin, MD, MPH

Principal Investigator

University of Virginia

Jyoti Patel, MD

Principal Investigator

University of Chicago

James Urbanic, MD

Principal Investigator

University of California, San Diego

David Kozono, MD

Principal Investigator

Alliance Foundation Trials, LLC.

Are You a Good Fit for This Trial?

Adults with stage IIIA/B Non-Small Cell Lung Cancer that can be removed by surgery. They must have good overall health, no prior lung cancer treatments or thoracic radiation, and not have certain autoimmune diseases or a history of other cancers within the last 2 years. Women who can bear children and men must agree to use contraception.

Inclusion Criteria

I am healthy enough for major lung surgery.

My organ and bone marrow functions are within normal ranges.

I agree to use birth control during and for 12 weeks after the study.

Exclusion Criteria

Your heart's electrical activity takes too long to reset itself, and this can be dangerous.

I have or had an autoimmune or inflammatory disorder.

I have moderate to severe numbness, tingling, or pain in my hands or feet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive durvalumab in combination with platinum doublet chemotherapy every 3 weeks

6-12 weeks

Every 3 weeks

Surgery

Participants undergo potentially curable surgery as per standard of care

1 week

Postoperative Radiation

Participants receive postoperative radiation (54Gy) within 4-10 weeks after surgery

4-10 weeks

Adjuvant Treatment

Participants receive adjuvant durvalumab 1500 mg IV every 4 weeks for 1 year

1 year

Every 4 weeks

Follow-up

Participants are monitored with imaging assessments every 12 weeks for 2 years, then every 6 months for 3 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Platinum Doublet Chemotherapy
• Radiotherapy
• Surgery

Trial Overview The trial tests if adding Durvalumab (an immune checkpoint inhibitor) to standard chemotherapy before and after surgery can improve outcomes for patients with operable lung cancer. It aims to clear cancer from lymph nodes better than chemotherapy alone.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 3 Interventions

Combined neoadjuvant platinum doublet chemotherapy plus durvalumab followed by surgery, postoperative radiation and adjuvant durvalumab for 13 cycles.

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?

Alliance Foundation Trials, LLC.

Lead Sponsor

Trials

25

Recruited

27,200+

AstraZeneca

Industry 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

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]

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, 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 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]

In a phase Ib study involving 136 patients, durvalumab (Du) combined with tremelimumab (Tr) and standard platinum-doublet chemotherapy was found to be safe, with most drug-related adverse events being mild (≤ grade 2) and primarily due to chemotherapy.

Among 73 patients with non-small cell lung cancer (NSCLC), the treatment achieved a 51% objective response rate, with a median progression-free survival of 6.5 months and overall survival of 19.8 months, indicating promising efficacy comparable to other immunotherapy and chemotherapy combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. Juergens, RA., Hao, D., Ellis, PM., et al.[2021]

In a study of 442 patients with unresectable stage III non-small cell lung cancer (NSCLC) who received platinum-based chemoradiotherapy, 50.3% were found eligible for durvalumab consolidation immunotherapy (CIT) according to PACIFIC trial criteria.

Despite only half of the patients meeting eligibility criteria, 85.6% of those eligible received CIT within a year of the drug's approval, with the main reasons for ineligibility being disease progression and low PD-L1 tumor proportion scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer-Cross-Sectional Study of Eligibility and Administration Rates. Eichkorn, T., Bozorgmehr, F., Regnery, S., et al.[2022]

In the phase III PACIFIC trial, durvalumab treatment led to a low incidence of immune-mediated adverse events (imAEs), with any-grade immune-mediated pneumonitis occurring in 9.4% of patients and grade 3/4 imAEs in only 3.4%.

Despite the occurrence of imAEs being more common with durvalumab compared to placebo, these events were generally manageable with treatments like corticosteroids, indicating that the benefits of the PACIFIC regimen outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Naidoo, J., Vansteenkiste, JF., Faivre-Finn, C., et al.[2022]

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]

Citations

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

Durvalumab after Chemoradiotherapy in Stage III Non– ... This phase 3 study compared the anti–programmed death ligand 1 antibody durvalumab as consolidation therapy with placebo in patients with stage III NSCLC

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

A phase II study of durvalumab (MEDI4736) immediately ... Durvalumab can be safely administered immediately after completion of CCRT for patients with unresectable stage III NSCLC, no additional or unexpected toxicity ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7244187/

Three-Year Overall Survival with Durvalumab after ... In the phase 3 PACIFIC study of patients with unresectable stage III NSCLC without progression after chemoradiotherapy, durvalumab demonstrated significant ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4646121/

Phase III, randomized, open-label study of durvalumab ... Platinum-based doublets are standard of care (SoC) first-line treatment for advanced NSCLC, but durable benefit is observed infrequently, ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04385368

NCT04385368 | Phase III Study to Determine the Efficacy ... The primary objective of this study is to assess the efficacy of durvalumab +SoC chemotherapy compared to placebo+ SoC chemotherapy as measured by DFS in all ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03519971

NCT03519971 | Study of Durvalumab Given With ... This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, international study assessing the efficacy and safety of durvalumab given ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924000765

First-line durvalumab in patients with PD-L1 positive ... Although data have shown improved survival with platinum doublets compared to single agent chemotherapy in PS 2 NSCLC pts and are preferred in the first-line ...