Durvalumab for Early Stage Non-Small Cell Lung Cancer

Overseen By Grace Hwang, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Stanford University

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Autoimmune disorders, Active infection, Organ transplant, others

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: 12

Duration: 12 months

80 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on ongoing chronic treatment with systemic immunosuppressive medication, except for certain low-dose or specific types like inhaled corticosteroids.

What data supports the effectiveness of the drug Durvalumab for early stage non-small cell lung cancer?

Durvalumab has shown significant improvements in overall survival and progression-free survival in patients with stage III non-small-cell lung cancer after chemoradiotherapy, as demonstrated in the PACIFIC trial. It has also shown clinical efficacy and a manageable safety profile in advanced non-small-cell lung cancer, particularly in patients with high PD-L1 expression. ^{1 2 3 4 5}

Is durvalumab safe for humans?

Durvalumab, also known as Imfinzi or MEDI4736, has been shown to have a manageable safety profile in various cancers, including non-small cell lung cancer. In a study, about 25% of patients experienced immune-related side effects, but severe cases were rare. It is generally considered safe, but like all treatments, it can have side effects. ^{1 2 3 6 7}

How is the drug durvalumab unique for treating early stage non-small cell lung cancer?

Durvalumab is unique because it is an immune checkpoint inhibitor that specifically blocks PD-L1, enhancing the body's immune response against cancer cells. It is particularly notable for its use as a consolidation treatment after chemoradiotherapy in stage III non-small cell lung cancer, which is not common for other treatments. ^{2 3 7 8 9}

What is the purpose of this trial?

In this study circulating tumor DNA (ctDNA) blood testing is used to detect the residual blood cancer. If residual cancer using this blood test is detected there may be at higher risk of having the cancer return. The study is going to test whether or not the number of circulating cancer cells detected in the blood can be reduced by administration durvalumab after the standard treatment if you are tested positive for the residual cancer.

Research Team

Joel W Neal, MD,PhD

Principal Investigator

Stanford Universiy

Eligibility Criteria

This trial is for adults over 18 with early-stage NSCLC who've completed surgery and/or radiation, possibly chemotherapy, but not immunotherapy. They must have no remaining cancer detectable except by ctDNA, be in good health with a life expectancy of at least 12 weeks, and agree to contraception. Those with certain mutations or other cancers under treatment can't join.

Inclusion Criteria

My cancer is between stages IA2 and IIIC, not including stage IA1 unless it has come back.

I or my partner will use effective birth control during and for 8 months after the study.

You are expected to live for at least 12 more weeks.

Exclusion Criteria

I have severe nerve pain or damage, but it might still be considered.

I do not have any ongoing infections.

I will need to continue taking medication to suppress my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants with detectable ctDNA (MRD+) receive up to 12 cycles of durvalumab, with ctDNA rechecked after 2 cycles

12 months

12 visits (in-person, every 28 days)

Follow-up

Participants are monitored for progression-free survival and overall survival

12 months

Treatment Details

Interventions

• Durvalumab

Trial Overview The study tests if Durvalumab can reduce the number of circulating cancer cells detected by AVENIO ctDNA Surveillance Kit in blood after standard treatment in patients showing minimal residual disease. It aims to prevent cancer recurrence by targeting these cells.

Participant Groups

Group I: Cohort 1 minimal residue disease positive(MRD+) Experimental Treatment 3 Interventions

Subjects with detectable ctDNA (MRD+) will receive up to 12 cycles of durvalumab (1500mg dose by intravenous (by vein) injection every 28 days). ctDNA will be re checked following 2 cycles (8 weeks) of durvalumab and compared to baseline levels. In the absence of progression or toxicity after 2 cycles, subject will continue with durvalumab to complete 1 year of treatment about 10 additional cycles). Subjects will be monitored for secondary endpoints of progression free survival (PFS) and overall survival (OS).

Group II: Cohort 2 minimal residue disease negative (MRD-) Active Control 2 Interventions

Subjects with undetectable ctDNA (MRD) will receive Standard of care and no treatment

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

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]

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]

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

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 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, 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 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]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. [2023]

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

Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. [2022]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Durvalumab for the treatment of non-small cell lung cancer. [2019]

8. England 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. [2022]

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

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