MEDI4736 for Lung Cancer

Not currently recruiting at 315 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Canadian Cancer Trials Group

Must not be taking: Immunosuppressants, Investigational drugs

Disqualifiers: Autoimmune disease, Cardiovascular conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new drug, MEDI4736 (an immunotherapy), effectively prevents lung cancer from returning after surgery and possibly chemotherapy. Participants will receive either MEDI4736 or a placebo to compare outcomes. This trial suits those who have had a complete surgical removal of primary non-small cell lung cancer meeting specific staging criteria. Participants should not have other types of lung cancer or a history of certain autoimmune diseases.

As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot be on immunosuppressive agents within 28 days of starting the trial, and you cannot receive live vaccines within 30 days prior to the trial.

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

Research shows that MEDI4736, also known as durvalumab, has undergone safety testing for lung cancer treatment. In earlier studies, patients received durvalumab after other treatments like chemotherapy. The results indicated it was generally well-tolerated, with most patients not experiencing serious side effects. Common mild side effects included fatigue and cough, which were manageable for most people.

Durvalumab is already approved for other types of lung cancer, demonstrating a history of safe use. This approval supports its safety. However, discussing potential risks and benefits with a healthcare provider remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about MEDI4736 for lung cancer because it represents a new class of treatment called immune checkpoint inhibitors. Unlike traditional chemotherapy, which targets cancer cells directly, MEDI4736 works by helping the immune system recognize and attack cancer cells. It specifically targets the PD-L1 protein, which some tumors use to hide from the immune system. This innovative approach has the potential to improve the body's natural defenses against cancer, offering hope for more effective and longer-lasting responses compared to existing treatments.

What evidence suggests that MEDI4736 might be an effective treatment for lung cancer?

Research shows that MEDI4736, also known as durvalumab, has promising results in treating certain lung cancers. Earlier studies found that durvalumab significantly increased the time patients lived without their cancer worsening. Specifically, patients with locally advanced, unresectable non-small-cell lung cancer (NSCLC) lived 11 months longer without cancer progression when treated with durvalumab compared to those who did not receive it. Additionally, long-term studies have shown better survival rates over five years for patients who received this treatment. In this trial, participants will receive either MEDI4736 or a placebo. These findings suggest that durvalumab could help improve survival after surgery and possibly chemotherapy for lung cancer patients. ^{2 6 7 8 9}

Who Is on the Research Team?

Glenwood Goss

Principal Investigator

Ottawa Hospital Research Institute, Ontario, Canada

Are You a Good Fit for This Trial?

This trial is for adults with a confirmed diagnosis of non-small cell lung cancer (NSCLC) who have had surgery and possibly chemo. They should be in good physical condition (ECOG 0 or 1), have adequate blood counts, and organ function. It's not for those with certain neuroendocrine carcinomas, other cancers within the last 5 years, autoimmune diseases, severe allergies to MEDI4736, or uncontrolled health conditions.

Inclusion Criteria

I am fully active or have some restrictions but can still care for myself.

I have N2 disease and will get radiation after surgery within the specified time.

Your white blood cell count and platelet count are within a certain range.

Exclusion Criteria

You have a history of certain immune-related diseases or organ transplant.

I have no cancer history in the last 5 years, except for non-melanoma skin cancer or in-situ cancer that was treated.

I have more than one primary cancer at the same time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MEDI4736 or placebo by intravenous infusion for a maximum of 12 months or until study drug withdrawal

12 months

Follow-up

Participants are monitored for disease-free survival and quality of life over an extended period

8 years

What Are the Treatments Tested in This Trial?

Interventions

• MEDI4736
• Placebo

Trial Overview The study is testing whether taking the new drug MEDI4736 after surgery (and maybe chemo) helps more than no additional treatment at all. Participants are randomly assigned to get either MEDI4736 or a placebo without knowing which one they're getting—a process known as double-blind.

How Is the Trial Designed?

Group I: MEDI4736 Experimental Treatment 1 Intervention

MEDI4736 by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier.

Group II: Placebo Placebo Group 1 Intervention

PLACEBO by intravenous infusion. Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Australasian Lung Cancer Trials Group

Collaborator

Trials

3

Recruited

1,600+

National Health and Medical Research Council, Australia

Collaborator

Trials

167

Recruited

473,000+

National Cancer Institute (NCI), Naples

Collaborator

Trials

1

Recruited

1,400+

Dutch Society of Physicians for Pulmonology and Tuberculosis

Collaborator

Trials

8

Recruited

3,100+

Thoracic Oncology Group of Australasia (TOGA)

Collaborator

Trials

1

Recruited

1,400+

Intergroupe Francophone de Cancerologie Thoracique

Collaborator

Trials

60

Recruited

42,500+

Central and Eastern European Oncology Group

Collaborator

Trials

5

Recruited

2,200+

Korean Cancer Study Group

Collaborator

Trials

33

Recruited

7,700+

Fundación GECP

Collaborator

Trials

22

Recruited

6,400+

Published Research Related to This Trial

In a phase I study involving 43 patients with advanced solid tumors, MEDI-573 demonstrated a favorable safety profile with no dose-limiting toxicities and only one case of treatment-related hyperglycemia.

While MEDI-573 did not lead to any partial or complete responses in the tumors, 13 out of 39 evaluable patients showed stable disease, indicating some preliminary antitumor activity in a heavily pretreated population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Haluska, P., Menefee, M., Plimack, ER., et al.[2021]

Immune checkpoint inhibitors, like pembrolizumab, have shown significant and lasting improvements in treating advanced non-small cell lung cancer (NSCLC), particularly in patients with high PD-L1 expression.

Pembrolizumab has been approved by the U.S. FDA for NSCLC that has progressed after other treatments, indicating its efficacy in a challenging patient population, but further research is needed to enhance treatment outcomes through combinations with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of pembrolizumab in the treatment of advanced non-small cell lung cancer. Santabarbara, G., Maione, P., Rossi, A., et al.[2021]

In a study involving 15 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone chemotherapy, the novel antitumor agent MGI-114 showed no objective tumor responses, leading to the conclusion that it is not effective as a second-line treatment.

The treatment was associated with significant side effects, including grade 2 or higher thrombocytopenia in 40% of patients, and grade 3 nausea and grade 2 vomiting in 40% and 47% of patients, respectively, indicating safety concerns with this dosing regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of 6-hydroxymethylacylfulvene (MGI-114, irofulven) in patients with advanced non-small cell cancer previously treated with chemotherapy. Dowell, JE., Johnson, DH., Rogers, JS., et al.[2019]

Canakinumab, an anti-IL-1β antibody, has shown promise in reducing lung cancer incidence, suggesting that targeting inflammation in the tumor microenvironment can enhance cancer treatment outcomes.

The CANOPY program is investigating the combination of canakinumab with PD-1 inhibition as a potential chemotherapy-free immunotherapy strategy, particularly for patients with non-small-cell lung cancer who typically have low PD-L1 expression levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming immunosuppression and pro-tumor inflammation in lung cancer with combined IL-1β and PD-1 inhibition. Lee, JM., Tsuboi, M., Kim, ES., et al.[2022]

In a phase III study involving 643 patients with advanced non-small-cell lung cancer, the addition of canakinumab to standard treatment did not significantly improve progression-free survival (PFS) or overall survival (OS) compared to placebo.

Despite the lack of survival benefit, canakinumab was found to delay the deterioration of lung cancer symptoms, indicating potential quality of life improvements for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Canakinumab Versus Placebo in Combination With First-Line Pembrolizumab Plus Chemotherapy for Advanced Non-Small-Cell Lung Cancer: Results From the CANOPY-1 Trial. Tan, DSW., Felip, E., de Castro, G., et al.[2023]

Citations

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

Durvalumab after Chemoradiotherapy in Stage III Non– ... Among patients with locally advanced, unresectable NSCLC, progression-free survival was 11 months longer among patients who received durvalumab ...

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

Durvalumab real-world treatment patterns and outcomes in ... Durvalumab real-world treatment patterns and outcomes in patients with stage III non-small-cell lung cancer treated in a US community setting.

3. 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 ...

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

Real World Effectiveness of Durvalumab in Stage III ... Five-year survival outcomes from the PACIFIC trial: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00036

The Phase III PACIFIC-2 Study | Journal of Clinical Oncology Immunotherapy targeting PD-L1 improves outcomes in patients with unresectable stage III non–small cell lung cancer (NSCLC) and no progression ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40835220/

Long-Term Safety and Effectiveness of Durvalumab in ... Based on the PACIFIC trial results, durvalumab after chemoradiotherapy (CRT) is the standard of care for unresectable stage III NSCLC.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02087423

NCT02087423 | A Global Study to Assess the Effects of ... This study is designed to investigate the efficacy, safety, tolerability of a new drug, MEDI4736 (Durvalumab), in patients with Locally Advanced or ...

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

A phase II clinical trial evaluating the safety and efficacy of ... Approximately 30–40% of patients with advanced and metastatic non-small cell lung cancer (NSCLC) present with an impaired performance status (PS).

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 ...