Quick Start Durvalumab for Lung Cancer

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must be taking: Platinum chemotherapy

Must not be taking: Tyrosine kinase inhibitors

Disqualifiers: Autoimmune disease, Congestive heart failure, 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: Unknown

Duration: 48 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how lung cancer responds to Durvalumab, a drug that helps the immune system fight cancer, when initiated soon after chemotherapy and radiation. Researchers aim to assess both the benefits and any side effects of this "quick start" approach. The trial targets individuals with Stage II or III nonsmall cell lung cancer who completed chemotherapy and radiation within the last two weeks. Participants should have tried other treatments but not certain targeted drugs and must be able to manage daily activities without severe breathing issues. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

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

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

Research has shown that Durvalumab is generally safe for patients with various solid cancers. When combined with tremelimumab, it maintains a manageable safety profile with few serious side effects.

In another study, patients received Durvalumab immediately after completing chemotherapy and radiation for unresectable stage III NSCLC (non-small cell lung cancer). The results indicated that patients tolerated Durvalumab safely without new or unexpected issues.

These findings suggest that Durvalumab is well-tolerated, though side effects can occur. Patients should consult their doctor to understand what this could mean for them. ^{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 chemotherapy, which directly kills cancer cells but can also damage healthy cells, durvalumab is an immunotherapy that blocks the PD-L1 protein. This action helps unleash the body's immune response against cancer cells, potentially leading to fewer side effects and more targeted destruction of cancerous tissues. Researchers are excited about durvalumab as it offers a different approach for treating lung cancer, potentially enhancing the effectiveness and safety of treatment.

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

Research has shown that Durvalumab, the treatment under study in this trial, can extend the lives of lung cancer patients. In one study, 83.1% of patients who received Durvalumab were alive after 12 months, compared to 75.3% of those who did not receive it. Another study found that starting Durvalumab within 14 days after chemotherapy and radiation improved the time patients lived without their cancer worsening and increased overall survival. These findings suggest that initiating Durvalumab soon after other treatments may be particularly effective. Overall, the evidence supports Durvalumab as a beneficial option for treating lung cancer, especially when used shortly after chemotherapy and radiation. ^{2 4 6 7 8}

Who Is on the Research Team?

Thomas Lycan

Principal Investigator

Wake Forest Baptist Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Stage III non-small cell lung cancer who've recently completed or are completing chemoradiation. They must have a life expectancy over three months, be able to use contraception if necessary, and sign informed consent. Excluded are those with uncontrolled symptoms, cancer progression during radiation, active autoimmune diseases requiring steroids, pregnancy/breastfeeding, certain heart conditions or mental illnesses affecting study compliance.

Inclusion Criteria

I can take care of myself and am up and about more than half of the day.

My condition cannot be treated with surgery.

I am undergoing or scheduled for specific radiation therapy for lung cancer, or I completed it recently.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I have had severe lung inflammation treated with high-dose steroids.

Patients who are pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants undergo chemotherapy and radiation therapy for Stage III nonsmall cell lung cancer

Varies

Treatment

Quick start of Durvalumab within 14 days of finishing chemoradiation

48 weeks

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab

Trial Overview The trial tests the effects of Durvalumab given within 14 days after finishing chemotherapy and radiation ('quick start'). It examines both positive and negative outcomes on patients' health and identifies logistical challenges in starting treatment promptly.

How Is the Trial Designed?

Group I: Quick Start Durvalumab Experimental Treatment 4 Interventions

Standard of care test and procedures for cancer treatments along with Durvalumab treatment at physician's discretion

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?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Published Research Related to This Trial

Durvalumab, a PD-L1 inhibitor, has shown promising results in increasing progression-free survival and objective response rates in patients with inoperable and locally advanced stage III non-small cell lung cancer, based on interim results from a phase III trial.

The significant benefits observed suggest that durvalumab could potentially become the standard treatment for these patients in the United States.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab Promising for NSCLC. [2019]

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]

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 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]

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 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 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 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]

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. 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 ...

3. 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 ...

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 ...