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

Trial Summary

What is the purpose of this trial?

This phase I trial aims to determine if it is safe to use palliative radiotherapy and lurbinectedin at the same time to treat small cell lung cancer that has spread outside of the chest and that has grown after being treated with chemotherapy (extensive stage). Lurbinectedin kills tumor cells by blocks a process called transcription that small cell lung cancer relies on to survive. It also damages the deoxyribonucleic acid (DNA) of tumor cells, which is similar to the way radiation kills tumor cells. Palliative radiotherapy is a routine medical treatment for patients who have lung cancer that has spread to other parts of the body (metastatic), and is used to relieve symptoms caused by cancer or to patients from developing symptoms. This trial may help doctors understand if treating patients with lurbinectedin and palliative radiotherapy at the same time would make them both work better than either one alone or if they could cause more side effects for patients when given together.

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.

What data supports the effectiveness of the drug Lurbinectedin for treating small cell lung cancer?

Lurbinectedin, also known as Zepzelca, was approved by the FDA in June 2020 as a treatment for small cell lung cancer (SCLC) that has progressed after initial chemotherapy. Early clinical trials have shown promising results, indicating that it can help manage this type of cancer. ^{1 2 3 4 5}

Is Lurbinectedin safe for humans?

Lurbinectedin, approved for treating small cell lung cancer, has an acceptable and manageable safety profile at the approved dose, but it includes warnings for potential side effects like myelosuppression (low blood cell counts), liver toxicity, and risks to unborn babies. ^{1 4 5 6 7}

What makes the drug Lurbinectedin unique for treating small cell lung cancer?

Lurbinectedin is unique because it is the first FDA-approved drug specifically for small cell lung cancer (SCLC) that has progressed after platinum-based chemotherapy, and it works by inhibiting oncogenic transcription (the process by which cancer cells grow and divide). ^{1 2 4 5 8}

Research Team

Kristin Higgins, MD

Principal Investigator

Emory University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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 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 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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment of Small Cell Lung Cancer with Lurbinectedin: A Review. [2022]

2. China 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. [2022]

3. England 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. [2020]

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

Lurbinectedin: First Approval. [2021]

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

Lurbinectedin: A New Treatment Option for Relapsed/Refractory Small-Cell Lung Cancer. [2021]

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

Pooled Safety Analysis of Single-Agent Lurbinectedin in Patients With Advanced Solid Tumours. [2023]

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

FDA Approval Summary: Lurbinectedin for the Treatment of Metastatic Small Cell Lung Cancer. [2022]

8. England 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. [2022]