MEDI4736 for Lung Cancer

Recruiting at 270 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

1415 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing whether a new drug, MEDI4736, can help lung cancer patients after surgery and possibly chemotherapy by boosting their immune system to fight any remaining cancer cells.

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.

What data supports the effectiveness of the drug MEDI4736 for lung cancer?

Research shows that MEDI4736, a type of drug called a monoclonal antibody, helps the immune system recognize and attack cancer cells by blocking a protein called PD-L1. It has shown promising early results in treating various cancers, including non-small cell lung cancer, and is being tested in several studies to confirm its effectiveness. ^{1 2 3 4 5}

Is MEDI4736 safe for human use?

MEDI4736, also known as durvalumab, has been studied for safety in various cancer types, including lung cancer. It generally has a better-tolerated safety profile compared to traditional chemotherapy, with ongoing studies to further assess its safety in combination with other treatments. ^{1 6 7 8 9}

How does the drug MEDI4736 differ from other treatments for lung cancer?

MEDI4736 is unique because it is a monoclonal antibody that blocks PD-L1, a protein that helps cancer cells hide from the immune system, allowing T cells to attack the tumor. Unlike traditional chemotherapy, it has a better safety profile and can be used alone or in combination with other treatments, offering a new approach for patients with non-small cell lung cancer. ^{1 6 10 11 12}

Research Team

Glenwood Goss

Principal Investigator

Ottawa Hospital Research Institute, Ontario, Canada

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

PD-L1 blockade for cancer treatment: MEDI4736. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3. [2023]

3. United States 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. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Overcoming immunosuppression and pro-tumor inflammation in lung cancer with combined IL-1β and PD-1 inhibition. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Surgical Perspective on Neoadjuvant Immunotherapy in Non-Small Cell Lung Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Immune checkpoint inhibitors in NSCLC. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

Present Situation and Future Progress of Inhaled Lung Cancer Therapy: Necessity of Inhaled Formulations with Drug Delivery Functions. [2021]

8. United States 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. [2019]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Retrospect and Prospect for Lung Cancer in China: Clinical Advances of Immune Checkpoint Inhibitors. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Identification and Characterization of MEDI4736, an Antagonistic Anti-PD-L1 Monoclonal Antibody. [2022]

12. China pubmed.ncbi.nlm.nih.gov

The role of pembrolizumab in the treatment of advanced non-small cell lung cancer. [2021]