Radiation + Durvalumab for Lung Cancer

(SUPER Trial)

Overseen By Marc de Perrot, MD, FRCSC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Marc de Perrot

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: EGFR/ALK mutations, Autoimmune disorders, Active infections, 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

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with stage 2 or 3 non-small cell lung cancer (NSCLC) who plan to undergo surgery. Participants will receive a mix of non-ablative oligofractionated radiation (a type of targeted radiation therapy) and Durvalumab, an immunotherapy drug, before surgery. The researchers aim to determine if this approach can shrink tumors and improve surgical outcomes. This trial suits those with stage IIB to IIIB NSCLC who have tumors that can be biopsied and are planning surgery. As a Phase 2 trial, the 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 does not specify if you need to stop taking your current medications. However, you cannot take any other cancer treatments while participating in this study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Durvalumab, also known as Imfinzi, is generally safe for treating non-small cell lung cancer (NSCLC). Studies have found it to be safe and well-tolerated in patients with various solid cancers, including lung cancer. Durvalumab has been tested in many patients and has demonstrated a good safety record, with common side effects usually being mild.

In the SUPER trial, Durvalumab was safely used with radiation therapy, supporting its use in this trial. Patients typically experience manageable side effects, and doctors closely monitor them during treatment. ^{1 2 3 4 5}

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

Researchers are excited about the combination treatment of radiation and durvalumab for lung cancer because it offers a unique approach compared to standard treatments like chemotherapy and surgery. Durvalumab is an immunotherapy drug that works by blocking PD-L1, a protein that allows cancer cells to evade the immune system. This mechanism boosts the body's ability to fight cancer. Additionally, the combination with non-ablative oligofractionated radiation therapy aims to enhance the immune response even further, potentially leading to better outcomes before surgery. This dual approach could provide more effective pre-surgical treatment, making it a promising option for lung cancer patients.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Studies have shown that Durvalumab, when combined with radiation, effectively treats non-small cell lung cancer (NSCLC). Earlier research found that individuals receiving Durvalumab after chemoradiotherapy lived three times longer without cancer progression compared to those who did not receive it. Durvalumab has also been proven to extend patients' lives. In this trial, participants will receive a combination of non-ablative oligofractionated radiation therapy and Durvalumab before surgery. This combination has demonstrated safety and effectiveness, particularly in advanced lung cancer, suggesting it could be a promising option for patients with stage 2 or 3 NSCLC. ^{2 3 6 7 8}

Who Is on the Research Team?

Marc de Perrot, MD, FRCSC

Principal Investigator

UHN - Toronto General Hopsital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage 2 or 3 non-small cell lung cancer who can consent to the study, have a life expectancy of at least 12 weeks, and are in good health with proper organ and marrow function. They must be able to follow the study plan including treatments and check-ups.

Inclusion Criteria

I am fully active or can carry out light work.

Adequate normal organ and marrow function as defined below Hemoglobin ≥9.0 g/dL Absolute neutrophil count (ANC) ≥1.0 × 10^9/L Platelet count ≥75 × 10^9/L Serum bilirubin in normal range with the exception of Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal

My body weight is over 30 kg.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Immunotherapy

Participants receive non-ablative oligofractionated radiation therapy and two cycles of Durvalumab before surgery

5-6 weeks

Surgery

Participants undergo surgical resection of the tumor

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Non-ablative oligofractionated radiation (NORT)

Trial Overview

The SUPER trial tests a combination treatment before surgery for lung cancer patients. It involves Non-ablative oligofractionated radiation (NORT) followed by two cycles of Durvalumab, an immunotherapy drug.

How Is the Trial Designed?

Group I: Neoadjuvant NORT-Durvalumab Experimental Treatment 2 Interventions

administration of non-ablative oligofractionated radiation therapy using 12 Gy in 3 fractions in combination with two doses of durvalumab (1500 mg IV) prior to surgery.

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?

Marc de Perrot

Lead Sponsor

Trials

2

Recruited

40+

Ozmosis Research Inc.

Industry Sponsor

Trials

25

Recruited

5,200+

Published Research Related to This Trial

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]

In the Phase 3 PACIFIC study involving 713 patients with unresectable stage III non-small-cell lung cancer (NSCLC), the anti-PD-L1 agent durvalumab significantly improved median progression-free survival (17.2 months vs. 5.6 months for placebo) and overall survival (not reached vs. 28.7 months for placebo).

While durvalumab showed a slight increase in grade 3 or 4 toxicity (30.5% vs. 26.1% for placebo), its efficacy in prolonging survival justifies its use, leading to its licensing for this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond chemoradiotherapy: improving treatment outcomes for patients with stage III unresectable non-small-cell lung cancer through immuno-oncology and durvalumab (Imfinzi®▼, AstraZeneca UK Limited). Patel, P., Alrifai, D., McDonald, F., et al.[2023]

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]

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]

This Phase II study (DOLPHIN) is investigating the safety and efficacy of durvalumab combined with radiation therapy in patients with unresectable, locally advanced non-small cell lung cancer (NSCLC) who are PD-L1 positive and unable to undergo chemotherapy, aiming for improved outcomes without the adverse effects of chemotherapy.

The primary goal is to evaluate the 12-month progression-free survival rate, with secondary goals including overall survival and safety, highlighting the potential of combining immunotherapy and radiotherapy for better treatment options in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design for a Multicenter, Phase II Study of Durvalumab Plus Concurrent Radiation Therapy in Locally Advanced Non-Small Cell Lung Cancer: The DOLPHIN Study (WJOG11619L). Tachihara, M., Tsujino, K., Ishihara, T., et al.[2021]

The DUART trial is a Phase II study investigating the safety and tolerability of durvalumab in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) who cannot undergo chemotherapy due to poor performance status or other health issues.

This study aims to evaluate whether durvalumab can improve survival outcomes for these patients compared to the current standard of care, which is radiotherapy alone, based on promising results from the PACIFIC trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DUART: durvalumab after radiotherapy in patients with unresectable, stage III NSCLC who are ineligible for chemotherapy. Filippi, AR., Dziadziuszko, R., García Campelo, MR., 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, 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 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]

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