Anti-Cancer Agents for Non-Small Cell Lung Cancer

(MAGELLAN Trial)

Not currently recruiting at 52 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AstraZeneca

Disqualifiers: Autoimmune disorders, Immunodeficiency, CNS metastases, others

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

Compensation: Varies

Number of Visits: 18

Duration: 48-54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness and safety of different cancer treatments for people with Stage IV Non-Small Cell Lung Cancer (NSCLC). It will explore various combinations of the drug durvalumab with other therapies, such as chemotherapy or new cancer drugs, to determine the most effective approach. The trial seeks participants with Stage IV NSCLC that cannot be treated with surgery or radiation and who have not received previous treatments for metastatic NSCLC. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive potentially groundbreaking therapies.

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

The trial does not specify if you need to stop taking your current medications, but it does require that you have not had any prior chemotherapy or systemic therapy for metastatic NSCLC.

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

Research has shown that durvalumab, whether used alone or with other treatments, has been tested in various studies. These studies generally find that durvalumab is well-tolerated, with most side effects being manageable. However, some patients have experienced immune-related reactions, which are common with cancer immunotherapies.

Studies have explored the combination of durvalumab and danvatirsen in treating different cancers, including non-small cell lung cancer. This combination has a safety profile similar to durvalumab alone, with side effects usually being mild to moderate.

The combination of durvalumab with oleclumab has also been studied. Results suggest this combination is generally safe, but some cases of more serious side effects require careful monitoring.

AZD2936, another treatment being tested in this trial, has an acceptable safety profile. Patients have experienced some side effects, but these are typically mild and manageable. When combined with chemotherapy, the safety profile remains similar, although chemotherapy can add its own side effects.

MEDI5752, a newer treatment option, has shown promising safety results. While many patients have tolerated it well, some have reported significant side effects, necessitating careful patient selection and monitoring.

This trial is in its early stages (Phase 1), focusing mainly on assessing safety and tolerability. While some evidence of safety exists, more data is needed to fully understand the risks and benefits. Discuss potential risks with a healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for non-small cell lung cancer because they offer innovative approaches compared to the standard chemotherapy options like carboplatin and cisplatin. For example, AZD2936 is an experimental drug that potentially enhances the effectiveness of chemotherapy by targeting specific cancer mechanisms. Durvalumab is an immunotherapy that helps the immune system recognize and attack cancer cells more effectively. MEDI5752 is a dual immunotherapy agent that combines two different mechanisms to boost the body's natural defenses against cancer. These treatments represent a shift towards personalized cancer therapies, aiming for better outcomes with potentially fewer side effects.

What evidence suggests that this trial's treatments could be effective for Stage IV Non-Small Cell Lung Cancer?

Research has shown that durvalumab, one of the treatments in this trial, can be effective for non-small cell lung cancer (NSCLC). Studies have found that durvalumab helps patients live longer without their cancer worsening. In this trial, some participants will receive durvalumab with other treatments like chemotherapy, which may enhance these benefits. Early trials suggested that adding danvatirsen to durvalumab might further improve treatment outcomes for advanced cancers. The combination of durvalumab and oleclumab, also being tested in this trial, has shown promise in reducing the risk of cancer growth.

AZD2936, another treatment under study in this trial, has shown early signs of fighting tumors in advanced NSCLC patients who have undergone previous treatments. This drug targets specific proteins that help cancer cells evade the immune system. MEDI5752, which targets two proteins uniquely, is also part of this trial and has demonstrated strong and lasting effects against tumors in some cancer studies. These findings suggest these treatments could potentially offer new options for people with NSCLC. ^{1 2 3 4 5}

Who Is on the Research Team?

Sandip Patel, MD

Principal Investigator

UCSD Morres Cancer Center

Chih-Hsin Yang, MD

Principal Investigator

National Taiwan University Hospital

Are You a Good Fit for This Trial?

This trial is for adults with Stage IV Non-Small Cell Lung Cancer (NSCLC) who haven't had systemic therapy for metastatic NSCLC. They should not have certain gene mutations treatable by approved drugs, must be in good physical condition (WHO/ECOG 0 or 1), and expected to live at least 12 weeks. People with autoimmune diseases, immunodeficiency, or untreated brain metastases can't join.

Inclusion Criteria

I haven't had chemotherapy or any treatment for my advanced lung cancer.

I know my tumor's PD-L1 status.

My cancer returned more than a year after completing platinum-based therapy.

Exclusion Criteria

I have or had an autoimmune or inflammatory disorder.

I have brain metastases that have not been treated.

I have not had chemotherapy or systemic therapy for advanced lung cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab and/or novel oncology therapies, with or without chemotherapy, for first-line Stage IV NSCLC

48-54 weeks

Tumor assessments every 6-9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3-6 months

Every 12 or 18 weeks depending on treatment arm

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• AZD2936
• Carboplatin
• Cisplatin
• Danvatirsen
• Durvalumab
• Gemcitabine
• MEDI5752
• Nab-paclitaxel
• Oleclumab
• Pemetrexed

Trial Overview The study tests the effectiveness and safety of durvalumab alone or combined with other new cancer treatments and chemotherapy options like Gemcitabine, Carboplatin, Nab-paclitaxel, Pemetrexed, Cisplatin for first-line treatment of advanced lung cancer.

How Is the Trial Designed?

Group I: B5 Experimental Treatment 4 Interventions

AZD2936 + chemotherapy

Group II: B4 Experimental Treatment 1 Intervention

MEDI5752

Group III: B3 Experimental Treatment 7 Interventions

Durvalumab + investigator's choice of chemotherapy + oleclumab

Group IV: B2 Experimental Treatment 7 Interventions

Durvalumab + Investigator's choice of chemotherapy + danvatirsen

Group V: B1 Experimental Treatment 6 Interventions

Durvalumab + Investigator's choice of chemotherapy

Group VI: A5 Experimental Treatment 1 Intervention

AZD2936

Group VII: A4 Experimental Treatment 1 Intervention

MEDI5752

Group VIII: A3 Experimental Treatment 2 Interventions

Durvalumab + oleclumab

Group IX: A2 Experimental Treatment 2 Interventions

Durvalumab + danvatirsen

Group X: A1 Experimental Treatment 1 Intervention

Durvalumab

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

In patients with metastatic non-small-cell lung cancer (NSCLC) expressing PD-L1 in ≥50% of tumor cells, pembrolizumab significantly improves progression-free and overall survival compared to traditional platinum-based chemotherapy.

Combining pembrolizumab with standard chemotherapy (pemetrexed and a platinum drug) enhances survival outcomes regardless of PD-L1 expression, indicating a broader efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. Wang, C., Kulkarni, P., Salgia, R.[2020]

In a study of 1,534 patients with advanced non-squamous non-small cell lung cancer, the combination of platinum/paclitaxel/bevacizumab resulted in a significantly higher overall response rate (ORR) of 40.8% compared to 32.7% for platinum/pemetrexed.

Despite the better ORR with the paclitaxel/bevacizumab regimen, there was no significant difference in progression-free survival (PFS) or overall survival (OS) between the two treatment groups, suggesting that both regimens are similarly effective and should be chosen based on side effect profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Chemotherapeutic Regimens Frequently Used in Metastatic Non-squamous NSCLC Treatment. Krejci, D., Opalka, P., Krejci, J., et al.[2021]

A variety of new agents, including taxanes, gemcitabine, and irinotecan, have shown promise in early clinical studies for treating non-small-cell lung cancer (NSCLC), indicating potential for improved treatment options.

Cisplatin remains a key component in combination therapies for NSCLC, being tested alongside these new agents, radiation, and surgery in numerous trials to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy in metastatic non-small-cell lung cancer. Sandler, A.[2022]

In the phase III KEYNOTE-189 study, pembrolizumab combined with pemetrexed and platinum-based chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) in patients with untreated metastatic nonsquamous non-small-cell lung cancer, with a hazard ratio of 0.56 for OS and 0.49 for PFS after a median follow-up of 31 months.

The treatment was associated with a high objective response rate (ORR) of 48.3% compared to 19.9% for the placebo group, and among patients who completed 35 cycles of pembrolizumab, the ORR was even higher at 85.7%, indicating strong efficacy with manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Rodríguez-Abreu, D., Powell, SF., Hochmair, MJ., et al.[2022]

The combination of pemetrexed and nab-paclitaxel was found to be feasible and well tolerated in patients with advanced non-small cell lung cancer (NSCLC), with a recommended phase II dose established at pemetrexed 500 mg/m² and nab-paclitaxel 260 mg/m².

In a phase II trial involving 37 patients, the treatment showed a response rate of 14% and a disease control rate of 46%, with a median overall survival of 8.8 months, indicating some efficacy in second and third-line therapy despite the early closure of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer. Ho, C., Davies, AM., Sangha, RS., et al.[2023]

Pemetrexed is an effective treatment for relapsed or chemotherapy-refractory non-small cell lung cancer (NSCLC), showing similar response and survival rates to taxotere but with less toxicity.

When combined with platinum analogs or other chemotherapy agents like gemcitabine or vinorelbine, pemetrexed produces equivalent responses and overall survival outcomes, suggesting it is a viable option in NSCLC treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of pemetrexed in non-small cell lung cancer. Longo-Sorbello, GS., Chen, B., Budak-Alpdogan, T., et al.[2022]

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

Cisplatin combined with either a vinca alkaloid or etoposide is highly effective in reducing mortality for patients with non-small cell lung cancer, as shown in meta-analyses comparing chemotherapy to supportive care.

Recent studies indicate that combining cisplatin-based chemotherapy with new agents and radiotherapy can significantly prolong survival and improve outcomes for patients with locally advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for non-small cell lung cancer]. Shinkai, T., Saijo, N.[2018]

In a randomized phase 2 trial involving 101 patients with stage IV lung adenocarcinoma, the combination of Pemetrexed and Cisplatin (Pem-Cis) showed a significantly higher one-year survival rate of 72.0% compared to 52.9% for Docetaxel and Cisplatin (Doc-Cis).

Patients receiving Pem-Cis also experienced longer progression-free survival (12.6 months) compared to those on Doc-Cis (7.5 months), indicating that Pem-Cis may be a more effective first-line treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. Su, SF., Li, M., Geng, YC., et al.[2020]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9050

experienced advanced/metastatic non-small-cell lung ... AZD2936 showed an acceptable safety profile and preliminary antitumor activity in pts with advanced/metastatic NSCLC previously treated with standard therapy ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)03314-8/fulltext

1446P Preliminary efficacy and safety of rilvegostomig ... Preliminary efficacy and safety of rilvegostomig (AZD2936), a bispecific antibody targeting PD-1 and TIGIT, in checkpoint inhibitor (CPI)-pretreated advanced/ ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04995523

NCT04995523 | A Study of AZD2936 Anti-TIGIT/Anti-PD-1 ... This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT400910

Safety, pharmacokinetics (PK), pharmacodynamics ( ... AZD2936 showed an acceptable safety profile and preliminary antitumor activity in pts with advanced/metastatic NSCLC previously treated with standard therapy ...

5. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7020C00001

A Study of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific ... This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and ...