Trilaciclib + Lurbinectedin for Small Cell Lung Cancer

Overseen By Lauren Higgins

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Investigational drugs

Disqualifiers: Active infection, Pregnant, Breastfeeding, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 8 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that certain medications or treatments are prohibited. It's best to discuss your current medications with the trial team to see if any are not allowed.

What data supports the effectiveness of the drug Lurbinectedin for Small Cell Lung Cancer?

Lurbinectedin has shown promising results in treating small cell lung cancer, especially for patients who have relapsed after initial treatment. In a phase II trial, it demonstrated a response rate of 35.2% and was approved by the FDA as a second-line treatment for this condition. ^{1 2 3 4 5}

Is the combination of Trilaciclib and Lurbinectedin safe for humans?

Lurbinectedin has been approved for treating small cell lung cancer and has shown a favorable safety profile in studies, with manageable side effects at the approved dose. Safety data from trials involving various solid tumors indicate that the drug is generally safe for human use. ^{3 4 5 6 7}

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

Lurbinectedin is unique because it is a marine-derived drug that specifically inhibits transcription (the process of copying DNA into RNA), which is often abnormal in small cell lung cancer. It was the first systematic therapy approved for this condition and has shown promising results both alone and in combination with other drugs. ^{4 5 6 8 9}

What is the purpose of this trial?

Lung cancer is by far the leading cause of cancer death among both men and women worldwide and the second most common cancer in terms of new cases. Small cell lung cancer (SCLC) is the deadliest form of lung cancer. The standard first-line treatment is the combination of carboplatin, etoposide, and atezolizumab. While response rates for this regimen are high (roughly 60%), the duration of response is short, typically 4 months. Following progression after the 1st line treatment of SCLC, there is no consensus regarding subsequent therapy. Lurbinectedin is FDA approved and is increasingly preferred in clinical practice. Toxicity was significant, but appeared favorable compared to historic results with topotecan, leading to the adoption of this therapy for second-line SCLC. The toxicity profile was dominated by myelosuppression. This study investigates the effect of Trilaciclib on myelosuppression rate in subjects with platinum refractory extensive stage (ES)- SCLC receiving Lurbinectedin as well as the clinical synergy of Trilaciclib and Lurbinectedin combination.

Research Team

Jared Weiss, MD

Principal Investigator

UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria

Adults over 18 with small cell lung cancer who've had previous platinum and PD1/PDL1 treatments can join. They need measurable disease, good performance status (able to carry out daily activities), and must consent to participate. Excluded are those on recent investigational drugs, certain medications, pregnant/breastfeeding women, anyone allergic to the study drugs or their components, or with active infections needing treatment.

Inclusion Criteria

I am fully active or can carry out light work.

Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.

I have been treated with a platinum-based drug or drugs targeting PD1/PDL1.

Exclusion Criteria

Treatment with any investigational drug within 4 weeks prior to start of treatment.

A known allergy or sensitivity to either study drug or its excipients.

Subject is receiving prohibited medications or treatments as listed in the protocol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Trilaciclib and Lurbinectedin to assess the effect on myelosuppression rate in subjects with platinum refractory extensive stage SCLC

Up to 8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including overall survival and progression-free survival

Up to 5 years

Treatment Details

Interventions

• Lurbinectedin
• Trilaciclib

Trial Overview The trial is testing Trilaciclib's ability to reduce myelosuppression (a decrease in bone marrow activity) in patients taking Lurbinectedin for extensive stage small cell lung cancer after other treatments have failed. It aims to see if combining these two drugs improves patient outcomes.

Participant Groups

Group I: Trilaciclib and Lurbinectedin Experimental Treatment 2 Interventions

Subjects with platinum refractory extensive stage small cell lung cancer receiving laciclib and Lurbinectedin

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?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

G1 Therapeutics, Inc.

Industry Sponsor

Trials

22

Recruited

3,300+

Findings from Research

Lurbinectedin treatment for small cell lung cancer (SCLC) showed improved median overall survival (OS) of 9.3 months compared to 6.1 months for the historical standard of care, based on a synthetic control arm analysis of 174 patients in Alberta, Canada.

The effectiveness of lurbinectedin was particularly notable in patients with a chemotherapy-free interval of 90 days or more, where the hazard ratio for improved survival was 0.49, indicating a significant survival benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Lurbinectedin for the Treatment of Relapsed Small Cell Lung Cancer in the Post-Platinum Setting: A Real-World Canadian Synthetic Control Arm Analysis. Boyne, DJ., Dawe, DE., Shakir, H., et al.[2023]

Lurbinectedin, a new treatment for small cell lung cancer (SCLC), showed a response rate of 35.2% in a phase II trial with patients who had previously failed chemotherapy, leading to its FDA approval for second-line treatment.

While a phase III trial combining lurbinectedin with doxorubicin did not improve overall survival compared to standard treatments, it demonstrated a better safety profile, indicating potential for further combination therapies with other agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lurbinectedin in small cell lung cancer. Manzo, A., Sforza, V., Carillio, G., 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, 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, a marine-derived drug, has shown promising efficacy in treating relapsed small cell lung cancer, both as a standalone treatment and in combination with other chemotherapy agents like doxorubicin and paclitaxel.

The drug has received accelerated approval from the FDA for monotherapy in relapsed small cell lung cancer, highlighting its favorable safety profile and potential as a new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lurbinectedin in the treatment of relapsed small cell lung cancer. Baena, J., Modrego, A., Zeaiter, A., et al.[2021]

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 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]

In a phase 3 trial involving 613 patients with relapsed small-cell lung cancer (SCLC), the combination of lurbinectedin and doxorubicin did not significantly improve overall survival compared to standard control therapies, with median survival times of 8.6 months versus 7.6 months, respectively.

However, the lurbinectedin plus doxorubicin combination demonstrated a better safety profile, with fewer severe hematological adverse events and lower rates of treatment discontinuation due to side effects compared to the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Aix, SP., Ciuleanu, TE., Navarro, A., et al.[2023]

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]

References

1. France pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Lurbinectedin for the Treatment of Relapsed Small Cell Lung Cancer in the Post-Platinum Setting: A Real-World Canadian Synthetic Control Arm Analysis. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Lurbinectedin in small cell lung cancer. [2022]

3. 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]

4. Netherlands pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Lurbinectedin in the treatment of relapsed small cell lung cancer. [2021]

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

Lurbinectedin: First Approval. [2021]

7. England pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. [2023]

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

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