Durvalumab + Radiotherapy for Stage III Non-Small Cell Lung Cancer

Overseen By Christian Chukwuma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Metastatic disease, Active infection, 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

Compensation: Varies

Number of Visits: 18

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of the drug Durvalumab (Imfinzi) and radiotherapy for treating Stage III Non-Small Cell Lung Cancer (NSCLC). The goal is to evaluate the treatment's effectiveness when surgery is not an option. Participants will receive both the drug and radiotherapy, followed by the drug alone for up to a year. This trial suits those diagnosed with inoperable Stage IIIA or IIIB NSCLC who have not previously received similar treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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

Research has shown that durvalumab, when combined with chest radiation therapy, is generally well-tolerated. Studies have found that durvalumab, a type of immunotherapy, is effective and safe as a follow-up treatment for patients with Stage III non-small cell lung cancer (NSCLC) after their initial treatment. One study indicated that it can be safely administered at a dose of 1500 mg every four weeks, which matches the dosage participants will receive in this trial.

Reported side effects often include tiredness, cough, and skin rash, common with many cancer treatments. However, serious side effects occur less frequently and are closely monitored by medical teams. Overall, existing research suggests that durvalumab, in combination with radiation therapy, is a safe option for many patients with Stage III NSCLC. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for Stage III Non-Small Cell Lung Cancer, which often includes chemotherapy combined with radiotherapy, durvalumab with radiotherapy takes a different approach by using immunotherapy. Durvalumab is a type of immune checkpoint inhibitor that specifically targets the PD-L1 protein, helping the immune system to better recognize and attack cancer cells. Researchers are excited about this treatment because it offers a potentially less toxic alternative to chemotherapy while aiming to enhance the body's own immune response to fight cancer more effectively. This combination could improve outcomes for patients by offering a more targeted approach with the added benefit of prolonged treatment beyond the initial radiotherapy phase.

What evidence suggests that Durvalumab and radiotherapy might be an effective treatment for Stage III Non-Small Cell Lung Cancer?

Research has shown that durvalumab, when used after combined chemotherapy and radiation therapy, helps patients with stage III non-small cell lung cancer (NSCLC) live longer. One study found that patients who received durvalumab had better survival rates than those who did not. Another study confirmed that durvalumab can be safely administered immediately after chemotherapy and radiation, with no unexpected side effects. In this trial, all participants will receive a combination of durvalumab and radiation therapy, which has proven to extend patient survival and is well-tolerated. These findings suggest that durvalumab effectively treats stage III NSCLC. ^{2 6 7 8 9}

Who Is on the Research Team?

Yuanyuan Zhang, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

Adults over 18 with stage IIIA or IIIB non-small cell lung cancer (NSCLC) that can't be operated on. They must have a life expectancy of at least 12 weeks, good organ function, and no severe illnesses or allergies to trial drugs. Women must not be pregnant and participants agree to use contraception.

Inclusion Criteria

My N2 disease was confirmed by a biopsy or a PET/CT scan.

My cancer is at a stage where surgery isn't an option due to large lymph nodes in my chest.

I had lung infection due to blockage but don't need IV antibiotics anymore.

Exclusion Criteria

You have a serious health problem, a history of certain medical conditions, a recent surgery, or are not using contraception during the study.

Receiving any other investigational agents for the treatment of the cancer under study

I've had radiation in the same area as my current cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Concurrent Treatment

Participants receive 1500mg intravenous durvalumab once every 4 weeks while receiving a 60 Gy/30 Fraction course of thoracic radiotherapy

6 weeks

6 visits (in-person)

Consolidative Treatment

Participants continue to receive 1500mg intravenous durvalumab once every 4 weeks for up to one year following the start of treatment

12 months

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Thoracic RT

Trial Overview This Phase II trial tests Durvalumab with thoracic radiotherapy followed by additional Durvalumab for NSCLC. It's a single-arm study where all eligible patients receive the same treatment without comparison groups.

How Is the Trial Designed?

Group I: Single Arm: Therapeutic Intervention Experimental Treatment 2 Interventions

All subjects receive the same therapeutic intervention of 1500mg intravenous durvalumab once every 4 weeks while receiving a 60 Gy/30 Fraction course of thoracic radiotherapy. After radiotherapy is complete, subjects continue to receive 1500mg intravenous durvalumab once every 4 weeks for up to one year following the start of treatment.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

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

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. imfinzihcp.com imfinzihcp.com/nsclc/stage-3/efficacy.html

IMFINZI® Efficacy for unresectable Stage III NSCLC Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. J Clin Oncol. 2022;40(12): ...

3. 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6831969/

Durvalumab for stage III non-small-cell lung cancer patients A recently published phase III trial (PACIFIC) showed for the first time an improved overall survival in stage III NSCLC patients with consolidative durvalumab.

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 ... Phase III open label first line therapy study of MEDI 4736 (durvalumab) with or without tremelimumab versus SOC in non small-cell lung cancer ( ...

7. imfinzihcp.com imfinzihcp.com/nsclc/stage-3/imfinzi-after-crt.html

IMFINZI® After CRT for unresectable Stage III NSCLC Durvalumab (IMFINZI) is recommended (Category 1) as a consolidation immunotherapy option for patients with unresectable Stage III NSCLC.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03693300

NCT03693300 | A Study to Determine Safety of ... This is a Phase II, open-label, multi-centre study to determine the safety of a fixed dose of Durvalumab (MEDI4736) (1500 mg) every 4 weeks [q4w] in ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.34.15_suppl.9029

Safety and clinical activity of durvalumab (MEDI4736), an ... A Phase 1/2 dose escalation and dose expansion study is ongoing to evaluate the safety and efficacy of durvalumab, a modified human IgG1 mAb ...