Chemotherapy + Durvalumab for Lung Cancer

Recruiting at 17 trial locations

Overseen By Quality Management and Compliance

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance Foundation Trials, LLC.

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

38 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm, phase II trial of combined neoadjuvant platinum doublet chemotherapy plus durvalumab followed by surgery, postoperative radiation and adjuvant durvalumab for 13 cycles for patients with potentially resectable stage IIIA and IIIB (T1-3, N2) NSCLC (per the 8th International Association for the Study of Lung Cancer classification). The primary objective of this study is to increase N2 nodal clearance (N2NC) to 50% or greater for combined platinum doublet chemotherapy with durvalumab induction therapy from historical rate of 30% for platinum doublet chemotherapy alone in patients with potentially resectable stage IIIA/B (N2) NSCLC.

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.

What data supports the effectiveness of the drug Durvalumab in treating lung cancer?

Durvalumab, when used alone or with chemotherapy, has shown promising results in treating non-small cell lung cancer (NSCLC), with a 51% response rate and a median survival of 19.8 months in a study. It is also approved as a follow-up treatment after chemo-radiotherapy in stage III NSCLC, indicating its effectiveness in this context. ^{1 2 3 4 5}

Is the combination of chemotherapy and durvalumab safe for humans?

Durvalumab, when used with chemotherapy, has shown a manageable safety profile in various studies. Most side effects were mild to moderate, but some serious ones like pneumonitis (lung inflammation), myocarditis (heart inflammation), and diarrhea were reported. There were also two treatment-related deaths, so while generally safe, there are risks involved. ^{1 3 4 6 7}

What makes the drug Durvalumab combined with chemotherapy unique for lung cancer treatment?

Durvalumab is a unique drug because it is an immune checkpoint inhibitor that blocks PD-L1, enhancing the body's immune response against cancer cells. When combined with platinum-doublet chemotherapy, it has shown promising results in treating non-small cell lung cancer, particularly in patients with high PD-L1 expression, offering a novel approach compared to traditional chemotherapy alone. ^{1 2 3 4 8}

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.

Eligibility Criteria

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

I have or had an autoimmune or inflammatory disorder.

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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 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]

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]

References

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

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

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

Durvalumab: First Global Approval. [2022]

3. Ireland 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. [2021]

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

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

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

Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context. [2020]

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

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]

7. Ireland 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. [2022]

8. Switzerland 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. [2022]