Durvalumab + Lurbinectedin for Small Cell Lung Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Pregnancy, CNS metastases, Active infections, others

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

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: 2

Duration: 6 months

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of combining two treatments, durvalumab and lurbinectedin, on small cell lung cancer that has returned or not responded to previous treatments. Durvalumab, a monoclonal antibody, may stop cancer cells from growing, while lurbinectedin helps slow their growth. The goal is to determine if these treatments together can kill more tumor cells and extend patients' lives. This trial suits those with small cell lung cancer that returned or didn’t respond after one round of specific chemotherapy and immunotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that durvalumab and lurbinectedin are likely to be safe for humans?

Research shows that durvalumab and lurbinectedin are being tested together to treat small cell lung cancer that has returned or not responded to previous treatments. Studies on lurbinectedin indicate it is generally well-tolerated. In earlier research, patients experienced some manageable side effects, such as fatigue, low blood cell counts, and nausea.

Durvalumab is already approved for other types of cancer and has a known safety record. It is usually well-tolerated, with common side effects like tiredness, cough, and skin rash. Serious side effects are less common but can include issues with the liver, lungs, or other organs.

The combination of these treatments is still under study, but current data suggests they are reasonably safe. This trial aims to provide more information about how patients handle the combination. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for small cell lung cancer?

Researchers are excited about combining durvalumab and lurbinectedin for small cell lung cancer because this duo offers a fresh approach compared to standard treatments like chemotherapy and immunotherapy alone. Durvalumab is an immunotherapy drug that helps the immune system target and attack cancer cells, while lurbinectedin disrupts the cancer cells' DNA, making it harder for them to survive and proliferate. This combination has the potential to enhance the body's natural defenses against cancer while simultaneously hindering cancer cell growth, which could lead to better outcomes for patients.

What evidence suggests that durvalumab and lurbinectedin might be an effective treatment for small cell lung cancer?

Research has shown that durvalumab, a monoclonal antibody, can extend the lives of patients with small cell lung cancer by enhancing the immune system's ability to attack cancer cells. Lurbinectedin, another drug, has proven effective in treating small cell lung cancer, particularly in patients who have already undergone other treatments. In real-world use, lurbinectedin has temporarily halted cancer growth. This trial will administer a combination of durvalumab and lurbinectedin, potentially killing more cancer cells and extending patient survival. ^{4 5 6 7 8}

Who Is on the Research Team?

Konstantinos Leventakos, MD

Principal Investigator

Mayo Clinic in Rochester

Anastasios Dimou, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• Lurbinectedin

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.

How Is the Trial Designed?

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 European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

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 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, 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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04607954

Durvalumab and Lurbinectedin for the Treatment of ... This phase II trial studies the effects of durvalumab and lurbinectedin in treating patients with extensive stage small cell lung cancer that has come back ...

2. imfinzihcp.com imfinzihcp.com/sclc/extensive-stage/efficacy.html

IMFINZI® (durvalumab) Efficacy & Clinical Trials for 1L ES- ... The ONLY FDA-approved IO combination in first-line ES-SCLC with 3-YEAR overall survival data from a randomized Phase III study

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40618675/

Outcome and safety of lurbinectedin as compassionate use ... Considering its safety profile and modest but consistent effectiveness, lurbinectedin represents a therapeutic option as compassionate use ...

4. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2024/imfinzi-improved-os-and-pfs-in-limited-stage-sclc.html

Imfinzi significantly improved overall survival and ... Imfinzi significantly improved overall survival and progression-free survival for patients with limited-stage small cell lung cancer in ADRIATIC ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40482375/

small cell lung cancer (ES-SCLC): real world response ... Lurbinectedin demonstrated meaningful clinical activity in second-line therapy for SCLC, while also showing durable responses in heavily pretreated cases.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02454972

NCT02454972 | Clinical Trial of Lurbinectedin (PM01183) ... Integrated exposure-response analysis of efficacy and safety of lurbinectedin to support the dose regimen in small-cell lung cancer. Cancer Chemother Pharmacol.

7. asco.org asco.org/abstracts-presentations/ABSTRACT254807

Efficacy and safety profile of lurbinectedin in second-line ... Efficacy and safety of lurbinectedin (PM1183) in small cell lung cancer (SCLC): Results from a phase 2 study. First Author: Jose Manuel Trigo Perez.

8. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/small-cell-lung-cancer

Small Cell Lung Cancer Clinical Trials The purpose of this study is to evaluate whether the combination of durvalumab plus lurbinectedin can increase 6 month progression-free survival, in patients ...