Durvalumab + Lurbinectedin for Small Cell Lung Cancer

Overseen by Anastasios Dimou, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Mayo Clinic

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Pregnancy, CNS metastases, Active infections, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial studies the effects of two drugs, durvalumab and lurbinectedin, on patients with advanced small cell lung cancer that has returned or not responded to previous treatments. Durvalumab boosts the immune system to fight cancer, and lurbinectedin stops cancer cells from growing. The goal is to see if this combination can help patients live longer without their cancer getting worse.

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, certain medications like live vaccines, recent chemotherapy, or immunosuppressive drugs may need to be paused before joining the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Durvalumab in treating cancer?

Durvalumab has shown effectiveness in improving survival rates in patients with locally advanced non-small cell lung cancer (NSCLC) after chemoradiotherapy, as seen in the PACIFIC trial. It is also approved for treating urothelial carcinoma, indicating its potential in enhancing immune responses against cancer cells. ^{1 2 3 4 5}

Is the combination of Durvalumab and Lurbinectedin safe for humans?

Durvalumab has been associated with an increased risk of immune-related side effects, particularly pneumonitis (inflammation of the lungs), which can be serious and potentially fatal. This safety information is based on its use in treating non-small cell lung cancer and other solid tumors. ^{1 3 4 6 7}

What makes the drug combination of Durvalumab and Lurbinectedin unique for treating small cell lung cancer?

The combination of Durvalumab and Lurbinectedin is unique because Durvalumab is an immunotherapy that enhances the body's immune response against cancer cells by blocking a protein called PD-L1, while Lurbinectedin is a chemotherapy drug that targets cancer cell DNA to prevent their growth. This dual approach of using both an immune system booster and a DNA-targeting agent is a novel strategy for treating small cell lung cancer. ^{1 6 8 9 10}

Research Team

Konstantinos Leventakos, MD

Principal Investigator

Mayo Clinic in Rochester

Anastasios Dimou, MD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults with small cell lung cancer that has returned or didn't respond to chemo and immunotherapy. Participants must have had only one prior treatment regimen, be in good health otherwise, and willing to use contraception. They can't join if they've had severe reactions to similar drugs, active infections or other cancers, certain heart conditions, or are pregnant/nursing.

Inclusion Criteria

Your bilirubin levels must be within a certain range, and this will be checked within two weeks before you join the study.

Your platelet count needs to be at least 100,000 per cubic millimeter.

My cancer returned more than 90 days after my last treatment, making it platinum-sensitive.

Exclusion Criteria

I have not had a heart attack in the last 6 months and do not need ongoing therapy for severe heart rhythm problems.

I have not had radiation therapy in the last 3 weeks.

I haven't taken immunosuppressive drugs in the last 14 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab and lurbinectedin IV on day 1 of each 21-day cycle

6 months

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 5 years

1 visit at 30 days post-treatment, then every 6 weeks until disease progression, and every 3 months thereafter

Treatment Details

Interventions

• Durvalumab (Monoclonal Antibodies)
• Lurbinectedin (Alkylating agents)

Trial Overview The trial tests Durvalumab (a monoclonal antibody) combined with Lurbinectedin (an alkylating agent) on patients with relapsed/refractory extensive stage small cell lung cancer. It aims to see if this combination helps control the disease better and improves survival rates.

Participant Groups

Group I: Treatment (durvalumab, lurbinectedin) Experimental Treatment 2 Interventions

Patients receive durvalumab IV over 60 minutes on day 1 and lurbinectedin IV over 60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Durvalumab is already approved in Japan for the following indications:

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Dr. Gianrico Farrugia

Mayo Clinic

Chief Executive Officer since 2019

MD from University of Malta Medical School

Dr. Richard Afable

Mayo Clinic

Chief Medical Officer

MD from Loyola Stritch School of Medicine

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Durvalumab is an FDA-approved monoclonal antibody that enhances T-cell responses against cancer by blocking the PD-L1 pathway, specifically for patients with advanced urothelial carcinoma who have progressed after platinum-based chemotherapy.

The drug is currently being tested in phase III trials for various cancers, including lung and head and neck cancers, indicating its potential broad application in oncology beyond urothelial carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. Syed, YY.[2022]

In a study of 68 patients with locally advanced non-small cell lung cancer treated with intensity-modulated radiotherapy (IMRT), the administration of durvalumab significantly improved distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS), with hazard ratios of 0.31, 0.33, and 0.32 respectively.

The study also found that while grade 2 or higher radiation pneumonitis (RP) was associated with worse DMFS, reducing the incidence of RP could enhance patient outcomes, highlighting the importance of managing treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. Yamamoto, T., Tsukita, Y., Katagiri, Y., et al.[2022]

Durvalumab has been approved for use in patients with locally advanced PD-L1-positive non-small cell lung cancer (NSCLC) after chemoradiotherapy, based on its efficacy demonstrated in the PACIFIC trial and subsequent analysis of 211 patients in the Expanded Access Program (EAP).

In the EAP, 126 patients who received durvalumab were included, some of whom had oligometastatic disease and a history of autoimmune conditions, indicating that durvalumab may be effective and safe for a broader patient population than previously studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. Faehling, M., Schumann, C., Christopoulos, P., et al.[2020]

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 a study of 34 patients with locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy followed by durvalumab, 26.5% experienced symptomatic pneumonitis, but this did not negatively affect their overall survival or progression-free survival.

The management of pneumonitis included steroid treatment, and 70% of patients were able to safely resume durvalumab after recovery, indicating that re-challenging with durvalumab is feasible even after pneumonitis occurs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of pneumonitis after chemoradiation and durvalumab for locally advanced non-small cell lung cancer. Hassanzadeh, C., Sita, T., Savoor, R., et al.[2022]

In a study of 924 patients with unresectable stage III non-small cell lung cancer treated with durvalumab, race did not significantly affect treatment patterns such as initiation delays, interruptions, or discontinuations.

Black patients experienced fewer immune-related adverse events and pneumonitis compared to White patients, suggesting potential differences in safety profiles between racial groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration. Moore, AM., Nooruddin, Z., Reveles, KR., et al.[2023]

In a study of 83 patients with unresectable stage III non-small cell lung cancer (NSCLC) receiving durvalumab, 25.3% experienced pneumonitis, confirming the risk associated with this treatment.

The incidence of pneumonitis observed in this real-world setting aligns with findings from the PACIFIC trial, indicating that the safety profile of durvalumab is consistent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. LeClair, JN., Merl, MY., Cohenuram, M., et al.[2022]

The AEGEAN trial is a phase III study involving approximately 800 patients with resectable, early-stage non-small-cell lung cancer (NSCLC) that aims to evaluate the effectiveness of durvalumab combined with chemotherapy before surgery and as a monotherapy after surgery.

This study will assess key outcomes such as pathological complete response and event-free survival, potentially improving treatment strategies for patients with Stage II-III NSCLC, where current survival rates remain low despite standard postoperative chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Rationale for a Phase III, Double-Blind, Placebo-Controlled Study of Neoadjuvant Durvalumab + Chemotherapy Followed by Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III non-small-cell Lung Cancer: The AEGEAN Trial. Heymach, JV., Mitsudomi, T., Harpole, D., et al.[2022]

In the IONESCO trial involving 46 patients with early-stage resectable non-small-cell lung cancer, neoadjuvant durvalumab treatment resulted in an impressive 89% complete surgical resection rate and a major histopathological response (MPR) of 19%.

Despite the promising efficacy, the trial faced an unexpected 90-day postoperative mortality rate of four patients, leading to its premature termination; however, no serious or grade 3-5 adverse events related to durvalumab were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO). Wislez, M., Mazieres, J., Lavole, A., 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. New Zealand pubmed.ncbi.nlm.nih.gov

Durvalumab: First Global Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP. [2020]

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

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

5. China pubmed.ncbi.nlm.nih.gov

Implications of pneumonitis after chemoradiation and durvalumab for locally advanced non-small cell lung cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration. [2023]

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

Real-World Incidence of Pneumonitis in Patients Receiving Durvalumab. [2022]

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

Design and Rationale for a Phase III, Double-Blind, Placebo-Controlled Study of Neoadjuvant Durvalumab + Chemotherapy Followed by Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III non-small-cell Lung Cancer: The AEGEAN Trial. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant durvalumab for resectable non-small-cell lung cancer (NSCLC): results from a multicenter study (IFCT-1601 IONESCO). [2022]

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

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