Durvalumab + Tremelimumab for Non-Small Cell Lung Cancer

(MYSTIC Trial)

Recruiting at 170 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids, Immunomodulatory therapy

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: 14

Duration: 48 weeks

1118 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus platinum-based SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type locally advanced or metastatic NSCLC

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you should not have had prior chemotherapy or systemic therapy for your lung cancer.

What data supports the effectiveness of the drug combination of Durvalumab and Tremelimumab for treating non-small cell lung cancer?

Research shows that the combination of Durvalumab and Tremelimumab, along with chemotherapy, significantly improved survival rates in patients with metastatic non-small cell lung cancer compared to chemotherapy alone. This combination has been approved for use in the USA for this condition, indicating its effectiveness. ^{1 2 3 4 5}

Is the combination of Durvalumab and Tremelimumab safe for humans?

The combination of Durvalumab and Tremelimumab has been studied in various cancers and is generally considered to have a tolerable safety profile, but it can lead to significant side effects. In a study, serious side effects occurred in about 32.6% of patients, including reduced appetite and diarrhea. It is important to discuss potential risks with a healthcare provider. ^{2 4 5 6 7}

How is the drug combination of Durvalumab and Tremelimumab unique for treating non-small cell lung cancer?

The combination of Durvalumab and Tremelimumab is unique because it uses two types of immune checkpoint inhibitors to enhance the body's immune response against cancer cells, potentially improving survival rates in patients with metastatic non-small cell lung cancer compared to standard chemotherapy alone. ^{1 3 4 5 8}

Research Team

Stuart McIntosh, MD

Principal Investigator

AstraZeneca, Alderley Park, Cheshire, UK

Naiyer Rizvi, MD

Principal Investigator

Columbia University Medical Center, New York, NY, USA

Eligibility Criteria

This trial is for adults over 18 with Stage IV NSCLC without EGFR mutations or ALK rearrangements, who haven't had systemic therapy for recurrent/metastatic NSCLC. Ideal candidates have a good performance status (0 or 1). It's not for those with certain lung cancer types, brain metastases/spinal issues unless stable and untreated, autoimmune/inflammatory disorders, or prior immunomodulatory therapy.

Inclusion Criteria

My cancer does not have EGFR mutations or ALK rearrangements.

I haven't received any treatment for my recurrent or metastatic NSCLC.

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

Exclusion Criteria

My lung cancer is a mix of small-cell and non-small cell types.

My brain or spinal metastases are stable and don't require steroids.

I have or had an autoimmune or inflammatory disorder like Crohn's disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or Standard of Care chemotherapy

48 weeks

Tumour scans every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Tumour scans every 8 weeks after 48 weeks until progression

Treatment Details

Interventions

• MEDI4736 (Durvalumab)
• Tremelimumab

Trial Overview The study tests the effectiveness and safety of MEDI4736 (Durvalumab) alone and combined with Tremelimumab versus standard platinum-based chemotherapy in first-line treatment. Patients are randomly assigned to receive either the new therapies or one of several chemo options.

Participant Groups

Group I: Monotherapy Experimental Treatment 1 Intervention

PD-L1 monoclonal Antibody monotherapy.

Group II: Combination Therapy Experimental Treatment 2 Interventions

PD-L1+Tremelimumab combination therapy

Group III: Standard of Care Active Control 5 Interventions

Standard of Care chemotherapy treatment

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

Findings from Research

In the phase 3 POSEIDON study involving 1013 treatment-naïve patients with metastatic non-small-cell lung cancer (NSCLC), the combination of tremelimumab, durvalumab, and chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Patients receiving the combination treatment also experienced a longer time to deterioration in quality of life and various symptoms, indicating better overall health status compared to those on chemotherapy, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). Garon, EB., Cho, BC., Luft, A., et al.[2023]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

In the phase 3 MYSTIC study involving 488 treatment-naïve patients with metastatic non-small-cell lung cancer, durvalumab alone or in combination with tremelimumab showed significant improvements in patient-reported outcomes (PROs) compared to chemotherapy, particularly in reducing fatigue and appetite loss.

Patients receiving durvalumab-containing treatments experienced a longer time to deterioration in quality of life and physical functioning, indicating that these treatments may help maintain better overall well-being without negatively impacting quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). Garon, EB., Cho, BC., Reinmuth, N., et al.[2022]

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]

Tremelimumab, a CTLA-4 blocking antibody, was approved in the USA in October 2022 for treating unresectable hepatocellular carcinoma (uHCC) in combination with durvalumab, marking a significant advancement in cancer therapy.

In November 2022, tremelimumab was also approved for metastatic non-small cell lung cancer (mNSCLC) when combined with durvalumab and platinum-based chemotherapy, indicating its broad potential in treating various malignant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremelimumab: First Approval. Keam, SJ.[2023]

The combination of durvalumab and tremelimumab in cancer treatment is associated with a higher incidence of severe adverse events (32.6%) compared to durvalumab alone (23.8%), indicating increased safety concerns with the combination therapy.

Patients receiving the combination therapy also experienced higher rates of specific side effects such as diarrhea (15.6% vs. 8.1%), rash (11.1% vs. 6.5%), and treatment discontinuation (18% vs. 3%), highlighting the need for careful monitoring and patient counseling regarding these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. Fahmy, O., Ahmed, OAA., Khairul-Asri, MG., et al.[2023]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with durvalumab, with or without tremelimumab, plus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer (POSEIDON). [2023]

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

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. [2022]

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

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). [2022]

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

Durvalumab for the treatment of non-small cell lung cancer. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Tremelimumab: First Approval. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Adverse Events and Tolerability of Combined Durvalumab and Tremelimumab versus Durvalumab Alone in Solid Cancers: A Systematic Review and Meta-Analysis. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]