Anti-Cancer Agents for Non-Small Cell Lung Cancer

(MAGELLAN Trial)

Recruiting at 39 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

175 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug AZD2936 and other drugs in the treatment of non-small cell lung cancer?

Research shows that combining platinum-based chemotherapy with checkpoint inhibitors like pembrolizumab significantly improves survival in non-small cell lung cancer (NSCLC) patients. Additionally, pemetrexed combined with platinum drugs or nab-paclitaxel has shown effectiveness in NSCLC treatment, providing similar survival outcomes with less toxicity compared to other regimens. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

The treatments involving pemetrexed, carboplatin, and cisplatin have shown acceptable safety profiles in clinical trials for non-small cell lung cancer. Pemetrexed, in particular, has been noted for having fewer side effects compared to some other treatments, and it is well-tolerated when used with radiation therapy. ^{1 2 6 7 8}

What makes the drug AZD2936 unique for treating non-small cell lung cancer?

The treatment AZD2936 is unique because it combines multiple agents, including novel drugs like Durvalumab and Oleclumab, which are not standard in traditional chemotherapy regimens for non-small cell lung cancer. This combination aims to enhance the effectiveness of treatment by targeting different pathways involved in cancer growth and survival. ^{9 10 11 12 13}

What is the purpose of this trial?

This study is designed to determine the efficacy and safety of durvalumab and/or novel oncology therapies, with or without chemotherapy, for first-line Stage IV Non-Small Cell Lung Cancer (NSCLC)

Research Team

Sandip Patel, MD

Principal Investigator

UCSD Morres Cancer Center

Chih-Hsin Yang, MD

Principal Investigator

National Taiwan University Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

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Combined Checkpoint Inhibition and Chemotherapy: New Era of 1st-Line Treatment for Non-Small-Cell Lung Cancer. [2020]

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Role of pemetrexed in non-small cell lung cancer. [2022]

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Comparison of Chemotherapeutic Regimens Frequently Used in Metastatic Non-squamous NSCLC Treatment. [2021]

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Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. [2022]

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Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

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Randomized phase II study of pemetrexed-cisplatin or docetaxel-cisplatin plus thoracic intensity-modulated radiation therapy in patients with stage IV lung adenocarcinoma. [2020]

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Pemetrexed in the treatment of advanced non-small-cell lung cancer: a review of the clinical data. [2019]

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