Durvalumab vs Chemotherapy for Non-Small Cell Lung Cancer

Not currently recruiting at 96 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids, Immunotherapy

Disqualifiers: Brain metastases, Autoimmune disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 6

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, durvalumab (an immunotherapy drug), against standard chemotherapy for people with advanced non-small cell lung cancer (NSCLC). The researchers aim to determine if durvalumab is more effective and safer for those who haven't yet received cancer treatment. Participants should have stage IV NSCLC without certain genetic changes (EGFR and ALK) and show high levels of a protein called PD-L1. This trial suits those untreated and experiencing symptoms related to advanced lung cancer. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

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

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

Research has shown that durvalumab is generally safe and well-tolerated for people with advanced non-small cell lung cancer (NSCLC). In earlier studies, common side effects included thyroid issues (12.5%), liver problems (7.2%), and colon inflammation (2.0%). Despite these side effects, many patients have used durvalumab safely.

For those considering chemotherapy options like gemcitabine, carboplatin, cisplatin, paclitaxel, or pemetrexed, these are standard treatments with known side effects. These can include low blood counts, nausea, and tiredness, but doctors understand them well.

Overall, both durvalumab and chemotherapy have safety profiles that doctors are familiar with, and they can guide patients on what to expect and how to manage any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about Durvalumab for non-small cell lung cancer because it works differently from traditional chemotherapy options. Unlike standard treatments, which often involve combinations like gemcitabine with carboplatin or cisplatin, Durvalumab is a monoclonal antibody that targets the PD-L1 protein on cancer cells. This immune checkpoint blockade can potentially boost the body's immune response to attack cancer cells more effectively. By harnessing the immune system, Durvalumab offers a promising alternative that might improve outcomes for patients with this type of lung cancer.

What evidence suggests that this trial's treatments could be effective for advanced NSCLC?

This trial will compare Durvalumab with standard chemotherapy treatments for non-small cell lung cancer (NSCLC). Studies have shown that Durvalumab, a medicine that aids the immune system in fighting cancer, can significantly benefit people with NSCLC. Specifically, research indicates that after using Durvalumab, 55.9% of patients experienced no cancer growth for a year. In another study, 83.5% of patients were alive after one year, and 64.0% were alive after two years, demonstrating a clear benefit in terms of survival. These findings suggest that Durvalumab can be a powerful option for treating advanced NSCLC, especially for patients with high levels of a protein called PD-L1. Meanwhile, the standard chemotherapy treatments in this trial include combinations such as Gemcitabine with carboplatin or cisplatin, Paclitaxel with carboplatin, and Pemetrexed with carboplatin or cisplatin. ^{2 6 7 8 9}

Who Is on the Research Team?

Shire Norah

Principal Investigator

AstraZeneca GMD IO, Gaitherburg, MD, USA

Parker Suzanne

Principal Investigator

AstraZeneca RDM, South San Francisco, USA

Are You a Good Fit for This Trial?

This trial is for adults with Stage IV Non-Small Cell Lung Cancer (NSCLC) who have not had prior treatment, do not have certain gene mutations (EGFR/ALK), and show high PD-L1 expression. It's not for those with a history of significant autoimmune diseases, untreated brain metastases, or previous immune therapy.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer shows high PD-L1 expression.

My condition is Stage IV non-small cell lung cancer.

Exclusion Criteria

I have stable brain or spinal metastases and haven't taken steroids for 14 days.

I have or had an autoimmune or inflammatory disorder like colitis.

I have not had chemotherapy or any systemic therapy for advanced NSCLC.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Durvalumab or standard of care platinum-based chemotherapy

12 months

Tumor assessments every 6 weeks for the first 48 weeks, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

57 months

Long-term Follow-up

Participants are assessed for overall survival and progression-free survival

Up to 69 months

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab (MEDI4736)
• Gemcitabine + carboplatin
• Gemcitabine + cisplatin
• Paclitaxel + carboplatin
• Pemetrexed + carboplatin
• Pemetrexed + cisplatin

Trial Overview The study compares the effectiveness and safety of Durvalumab alone versus various combinations of chemotherapy drugs in first-line treatment. Patients are randomly assigned to receive either Durvalumab or one of several standard chemo options.

How Is the Trial Designed?

Group I: Arm 1: Durvalumab Experimental Treatment 1 Intervention

Anti-PD-L1 monoclonal Antibody monotherapy

Group II: Arm 2: Standard of Care Active Control 5 Interventions

Standard of Care Platinum-Based chemotherapy

Who Is Running the Clinical Trial?

AstraZeneca

Lead 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37497677/

Durvalumab real-world treatment patterns and outcomes in ... Estimated 1- and 2-year OS rates were 83.5 and 64.0%, respectively, with median OS not reached. Conclusion: This study confirmed an OS benefit ...

2. jto.org jto.org/article/S1556-0864(25)01014-7/fulltext

Long-Term Safety and Effectiveness of Durvalumab in ... Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709937

Durvalumab after Chemoradiotherapy in Stage III Non– ... The 12-month progression-free survival rate was 55.9% (95% CI, 51.0 to 60.4) with durvalumab and 35.3% (95% CI, 29.0 to 41.7) with placebo, and ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40075721/

Real-World Insights into the Impact of Durvalumab on ... The PACIFIC trial demonstrated that durvalumab after platinum-based chemoradiotherapy (CRT) improves overall survival (OS) and progression-free survival (PFS).

5. sciencedirect.com sciencedirect.com/science/article/pii/S1879406824000031

Real world efficacy and toxicity of consolidation ... Consolidation durvalumab following platinum-based chemoradiotherapy (CRT) significantly improved overall survival for patients with unresectable stage III ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39147210/

Concerning Safety and Efficacy of Concurrent and ... - PubMed The primary endpoint of progression-free survival at 12 months was 20% (50% for PDL1≥1% vs 0% for PDL1 unavailable or <1%). Median overall ...

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00494-7/fulltext

A phase II clinical trial evaluating the safety and efficacy of ... This study demonstrates that single agent durvalumab is safe and well tolerated in the 1st line treatment of patients with advanced NSCLC and ECOG PS of 2, with ...

8. clinical-lung-cancer.com clinical-lung-cancer.com/article/S1525-7304(25)00154-8/fulltext

Real World Effectiveness of Durvalumab in Stage III ... Survival outcomes favored durvalumab over the historic cohort across PD-L1 subgroups, though PFS improvement was not statistically significant ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.01308

Five-Year Survival Outcomes From the PACIFIC Trial Analyses of patient-reported outcomes from PACIFIC found no evidence for a detrimental effect of up to 12 months of durvalumab treatment on ...