Durvalumab + Tremelimumab for Non-Small Cell Lung Cancer

(MYSTIC Trial)

Not currently recruiting at 215 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for advanced non-small cell lung cancer (NSCLC) to determine if they outperform standard chemotherapy. It examines the use of two drugs, durvalumab and tremelimumab (both immunotherapy drugs), either in combination or with durvalumab alone, compared to typical chemotherapy. The goal is to identify the most effective and safe treatment for patients. Suitable participants have stage IV NSCLC without specific genetic mutations (EGFR or ALK) and have not previously received chemotherapy or similar treatments. As a Phase 3 trial, this research represents the final step before FDA approval, providing patients access to potentially groundbreaking treatments.

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.

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

Research shows that durvalumab, when used alone, is generally safe and well-tolerated for treating advanced non-small cell lung cancer (NSCLC). The most common side effects include thyroid problems (12.5%), liver issues (7.2%), and colitis (2.0%), which is inflammation of the colon. These side effects are usually mild and manageable.

Specific safety details for the combination of durvalumab and tremelimumab aren't provided here. However, since this trial is in a later stage, earlier studies likely demonstrated that the combination was safe enough to continue. It is also reassuring that durvalumab is already approved for other conditions, indicating its safety is well-understood.

Prospective trial participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Durvalumab and Tremelimumab for non-small cell lung cancer because they work differently from traditional chemotherapy. Unlike standard treatments like cisplatin or carboplatin, which target rapidly dividing cells, Durvalumab and Tremelimumab are immunotherapy drugs that help the immune system recognize and attack cancer cells. Durvalumab targets the PD-L1 protein, while Tremelimumab inhibits CTLA-4, both of which are pathways cancer cells use to hide from the immune system. This novel approach could lead to more effective and potentially longer-lasting responses in patients.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will compare different treatment approaches for non-small cell lung cancer (NSCLC). Studies have shown that Durvalumab, one of the treatments participants may receive as monotherapy, can greatly improve survival rates in patients with NSCLC. In one study, 83.5% of patients were alive after one year, and 64.0% were alive after two years. Another study found that using Durvalumab after initial treatment with chemotherapy and radiation helped patients live longer and delayed cancer progression. Although specific data on the combination of Durvalumab and Tremelimumab in this trial is not available, the success of Durvalumab alone suggests it might work well when combined with Tremelimumab, another treatment option being tested. Both treatments aim to help the immune system fight cancer, which has shown promise in improving patient outcomes. ^{2 6 7 8 9}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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, 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]

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 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]

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]

Citations

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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 ...