Lurbinectedin + Radiotherapy for Small Cell Lung Cancer

Recruiting at 2 trial locations

Overseen By Kristin Higgins, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must be taking: Lurbinectedin

Disqualifiers: Pregnancy, Breastfeeding, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 21 days

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining lurbinectedin, a drug that disrupts cancer cell growth, with palliative radiotherapy can more effectively treat small cell lung cancer that has spread beyond the chest and progressed after initial chemotherapy. The main goal is to determine if using the drug and radiation together is more effective or has more side effects than using them separately. The trial seeks participants with extensive-stage small cell lung cancer that has not responded to initial treatments and who are suitable for lurbinectedin therapy. 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 this new treatment combination.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have completed all previous cancer-directed therapies (except lurbinectedin) at least 3 weeks before starting the study therapy.

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

Research has shown that lurbinectedin is generally well-tolerated by patients with advanced small cell lung cancer. In earlier studies, patients who received lurbinectedin for compassionate use experienced mostly mild side effects, meaning most did not have severe reactions.

One study with 238 patients used lurbinectedin as a second or third treatment option after other therapies. Patients typically received about three treatment cycles, suggesting many could continue treatment without major problems.

Although lurbinectedin is not yet approved for all uses, it has FDA approval for treating certain lung cancers, providing some assurance about its safety. This trial aims to determine if using it with radiotherapy is equally safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for small cell lung cancer?

Researchers are excited about lurbinectedin for small cell lung cancer because it offers a new way to tackle the disease by targeting the transcription process necessary for cancer cell survival. Unlike standard treatments like chemotherapy and immunotherapy, lurbinectedin is a novel compound that disrupts cancer cell replication. Additionally, combining it with palliative radiotherapy could enhance its effectiveness, potentially offering better outcomes for patients with advanced stages of this aggressive cancer.

What evidence suggests that this treatment might be an effective treatment for small cell lung cancer?

Research has shown that lurbinectedin, administered alongside palliative radiation therapy in this trial, may help treat small cell lung cancer (SCLC), especially after other treatments have been attempted. In earlier studies, lurbinectedin proved effective, offering lasting benefits for patients who had undergone multiple treatments. The drug halts transcription, a process cancer cells need to survive, and damages their DNA, similar to radiation. These actions suggest that lurbinectedin can effectively target and destroy cancer cells, potentially improving outcomes for people with advanced SCLC. ^{2 3 5 6 7}

Who Is on the Research Team?

Kristin Higgins, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

Adults with extensive stage small cell lung cancer that has spread and grown after chemotherapy can join this trial. They must have proper liver, blood, and bone marrow function, not be pregnant or breastfeeding, agree to use contraception, and have an ECOG performance status of 3 or less (which means they are capable of limited self-care).

Inclusion Criteria

I understand my cancer diagnosis and the risks and benefits of the study.

I am not pregnant and can prove it with a test before starting treatment.

I agree to use birth control during and after the study as required.

Exclusion Criteria

I had radiation therapy, but my current cancer treatment area is not close to previously treated critical areas.

Pregnancy or breastfeeding within 2 weeks

Patients may not enroll in both safety cohorts

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo palliative radiotherapy over 5 or 10 treatment fractions daily for 21 days and receive lurbinectedin intravenously on day 1 of each cycle, with cycles repeating every 21 days

21 days

Daily visits for radiotherapy, 1 visit every 21 days for lurbinectedin

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 1, 3, 6, and 12 months

12 months

4 visits (in-person) at 1, 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Lurbinectedin
• Palliative Radiation Therapy

Trial Overview

The trial is testing the safety of combining lurbinectedin (a drug that disrupts cancer cell DNA) with palliative radiotherapy in patients whose lung cancer has metastasized. The goal is to see if using them together improves effectiveness without increasing side effects.

How Is the Trial Designed?

Group I: Treatment (lurbinectedin and palliative radiation therapy) Experimental Treatment 2 Interventions

Patients undergo palliative RT over 5 or 10 treatment fractions at the discretion of the treating physician daily for 21 days. Patients also receive lurbinectedin IV over 1 hour on day 1 of each cycle. Cycles of lurbinectedin repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Lurbinectedin is already approved in United States, European Union for the following indications:

Approved in United States as Zepzelca for:

• Metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Approved in European Union as Zepzelca for:

• Metastatic small-cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Jazz Pharmaceuticals

Industry Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Published Research Related to This Trial

Lurbinectedin (ZEPZELCA™) has been approved in the USA for treating adult patients with metastatic small cell lung cancer (SCLC) who have progressed after platinum-based chemotherapy, highlighting its efficacy in a challenging cancer type.

The drug has received orphan drug status in multiple countries, indicating its potential importance in treating rare cancers, and ongoing clinical investigations are exploring its use in other solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lurbinectedin: First Approval. Markham, A.[2021]

Lurbinectedin, approved by the FDA in June 2020 as ZEPZELCA, is the first systemic therapy specifically for Small Cell Lung Cancer (SCLC), highlighting its significance in cancer treatment.

The drug works by inhibiting the transcription of genes related to tumor growth, which helps to suppress tumor-associated macrophages and alter the tumor environment, making it a promising option for SCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Small Cell Lung Cancer with Lurbinectedin: A Review. Rajput, PS., Khan, SR., Singh, P., et al.[2022]

Lurbinectedin shows significant cytotoxicity in small cell lung cancer (SCLC) cell lines, particularly at low doses, with a median IC50 of 0.46 nM, and its effectiveness is enhanced in cell lines expressing high levels of the SLFN11 protein, which serves as a promising biomarker for sensitivity to this treatment.

In SCLC models with low SLFN11 expression, combining lurbinectedin with ATR inhibitors like ceralasertib and berzosertib can resensitize these otherwise resistant cells, suggesting a potential strategy to improve treatment outcomes for patients with low SLFN11 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SLFN11 biomarker status predicts response to lurbinectedin as a single agent and in combination with ATR inhibition in small cell lung cancer. Kundu, K., Cardnell, RJ., Zhang, B., et al.[2022]

Lurbinectedin shows a promising overall response rate of 35.2% and a median overall survival of 9.3 months as a second-line therapy for small-cell lung cancer (SCLC), making it a viable option for patients who have not responded to platinum-based treatments.

Common adverse effects include myelosuppression, increased liver enzymes, nausea, vomiting, and fatigue, with significant drug interactions noted, particularly with CYP3A4 inhibitors, highlighting the need for careful management and monitoring in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lurbinectedin: A New Treatment Option for Relapsed/Refractory Small-Cell Lung Cancer. Shinn, LT., Vo, KA., Reeves, DJ.[2021]

Lurbinectedin received accelerated FDA approval for treating metastatic small cell lung cancer (SCLC) in patients who progressed after platinum-based chemotherapy, based on a study of 105 patients showing a 35% overall response rate and a median duration of response of 5.3 months.

This approval is significant as it is the first new treatment option for metastatic SCLC in over 20 years, particularly addressing the needs of patients with platinum-resistant disease, although it comes with warnings for potential side effects like myelosuppression and hepatotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lurbinectedin for the Treatment of Metastatic Small Cell Lung Cancer. Singh, S., Jaigirdar, AA., Mulkey, F., et al.[2022]

In a study of 95 patients with small cell lung cancer (SCLC) and malignant pleural mesothelioma (MPM) treated with lurbinectedin, the drug demonstrated a manageable safety profile and showed clinical activity, with median overall survival of 7.0 months for SCLC and 7.2 months for MPM.

Lurbinectedin was associated with immune system changes, including the depletion of classical monocytes and increased proliferation of T cells, suggesting its potential as a platform for future immunotherapy combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lurbinectedin shows clinical activity and immune-modulatory functions in patients with pre-treated small cell lung cancer and malignant pleural mesothelioma. Dumoulin, DW., Cantini, L., Cornelissen, R., et al.[2022]

Lurbinectedin has a manageable safety profile when used at the approved dose of 3.2 mg/m2 every 3 weeks, as shown in a pooled analysis of 554 patients with various advanced solid tumors, including small cell lung cancer and ovarian cancer.

The most common side effects were transient hematological abnormalities, particularly neutropenia (41%) and leukopenia (30%), along with non-hematological issues like fatigue (63%) and nausea (57%), indicating that while side effects are present, they are generally manageable for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. Leary, A., Oaknin, A., Trigo, JM., et al.[2023]

Lurbinectedin, which works by inhibiting the transcription of protein-coding genes and causing DNA damage, is being tested in a Phase III study (ATLANTIS) for its effectiveness in treating small-cell lung cancer after platinum-based chemotherapy.

The study compares the combination of lurbinectedin and doxorubicin against standard chemotherapy options, with overall survival as the primary goal, involving patients who have already undergone one line of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ATLANTIS: a Phase III study of lurbinectedin/doxorubicin versus topotecan or cyclophosphamide/doxorubicin/vincristine in patients with small-cell lung cancer who have failed one prior platinum-containing line. Farago, AF., Drapkin, BJ., Lopez-Vilarino de Ramos, JA., et al.[2020]

Citations

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pubmed.ncbi.nlm.nih.gov

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

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Lurbinectedin demonstrated meaningful clinical activity in second-line therapy for SCLC, while also showing durable responses in heavily pretreated cases.

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Outcome and safety of lurbinectedin as compassionate use ...

A total of 238 patients receiving lurbinectedin as second- (37 %), third- (45 %) or further-line (18 %) were included. Median number of cycles was 3 (1−22).

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pubmed.ncbi.nlm.nih.gov

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

Outcome and safety of lurbinectedin as compassionate use ...

Lurbinectedin has recently emerged in the treatment landscape of extensive stage (ES) small cell lung cancer (SCLC). Here we report the outcomes ...

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Real-World Lurbinectedin Exhibits Safety and Modest ...

Lurbinectedin (Zepzelca) displayed a favorable safety profile and modest efficacy outcomes as a therapy with compassionate use in patients with extensive-stage ...