Lurbinectedin + Osimertinib for Small Cell Lung Cancer

(LOTS Trial)

Overseen By Lori Tyson, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Misty Shields

Must be taking: Osimertinib

Disqualifiers: Pregnancy, Brain metastases, ILD, others

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

Compensation: Varies

Number of Visits: 2

Duration: Until progression or unacceptable toxicities

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination to determine its safety and effectiveness against a rare form of lung cancer called transformed small cell lung cancer (SCLC). The drugs under study are lurbinectedin (a chemotherapy drug) and osimertinib (a targeted therapy), each designed to target cancer cells in unique ways. The trial seeks individuals initially diagnosed with a type of lung cancer involving changes in the EGFR gene who have previously taken osimertinib. Those who have transitioned to SCLC and have not experienced changes rendering osimertinib ineffective may be suitable candidates. Participants should be willing to try new treatments and have measurable cancer that can be tracked during the trial. 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 combination therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does allow interruptions of osimertinib before enrollment. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of lurbinectedin and osimertinib has a predictable safety profile. In one study, all three patients experienced a decrease in bone marrow activity, but none faced severe issues. The FDA has already approved lurbinectedin for treating small cell lung cancer (SCLC) in patients who have previously received platinum-based therapy, indicating it is generally well-tolerated.

Osimertinib is a known treatment for certain types of lung cancer, which confirms its recognized safety record. It is important to note that this trial is in the early stages, with the primary goal of determining the treatment's safety for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Lurbinectedin and Osimertinib for small cell lung cancer because these drugs offer a novel approach compared to traditional chemotherapy. Lurbinectedin works by inhibiting the transcription process in cancer cells, which stops them from replicating, while Osimertinib is a targeted therapy that blocks specific proteins involved in cancer cell growth. This combination has the potential to be more effective and cause fewer side effects than the typical chemotherapy regimens. Additionally, the targeted nature of Osimertinib offers hope for personalized treatment, potentially leading to better outcomes for patients.

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

Research has shown that combining lurbinectedin and osimertinib might be promising for treating transformed small cell lung cancer (SCLC). One study found that patients receiving this combination after their cancer transformed to SCLC lived for a median of 7.7 months, meaning half of the patients lived longer. The treatment continued for a median of 4.3 months, the duration before it stopped working or side effects became too severe. Although data is limited, these early results suggest the combination might help slow this aggressive cancer. Participants in this trial will receive varying doses of lurbinectedin and osimertinib to further evaluate the combination's effectiveness and safety. ^{1 6 7 8 9}

Who Is on the Research Team?

Misty D Shields, MD, PhD

Principal Investigator

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with a rare cancer type known as transformed small cell lung cancer (SCLC). Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

Ability to provide written informed consent and HIPAA authorization

Measurable disease per RECIST (version 1.1)

Adequate laboratory functions on baseline testing within 21 days of enrollment including hematologic, hepatic, and renal parameters

Exclusion Criteria

Pregnant or breastfeeding patients

Severe allergic or anaphylactic reaction to osimertinib

Allergic or anaphylactic reactions to inactive ingredients of lurbinectedin

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Phase I dose de-escalation to identify the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs) of lurbinectedin and osimertinib

21 days

1 visit every 21 days

Treatment

Participants receive a combination of lurbinectedin every 21 days and osimertinib daily until progression or unacceptable toxicities

Until progression or unacceptable toxicities

1 visit every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lurbinectedin
• Osimertinib

Trial Overview The trial is testing the combination of two drugs: lurbinectedin and osimertinib. It's an open-label study, meaning both researchers and participants know which treatment is being administered.

How Is the Trial Designed?

Group I: Phase II Dose Expansion Experimental Treatment 2 Interventions

3.2 mg/m2 or 2.6 mg/m2 dose of lurbinectedin with 80 mg or 40 mg daily dose of osimertinib. This will occur day 1 of each 21 day cycle.

Group II: Phase I Does De-Escalation Experimental Treatment 2 Interventions

3.2 mg/m2 or 2.6 mg/m2 dose of lurbinectedin with 80 mg or 40 mg daily dose of osimertinib. This will occur day 1 of each 21 day cycle.

Who Is Running the Clinical Trial?

Misty Shields

Lead Sponsor

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07153055

Phase I/II Trial of Lurbinectedin With Osimertinib in ... This open-label, Phase I/II trial is studying the safety and effectiveness of an experimental drug combination, lurbinectedin with osimertinib, ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2666364325000232

Brief Report Combination of Lurbinectedin and Osimertinib ... In this case series, three patients received treatment with lurbinectedin plus osimertinib after transformation to SCLC. In our limited experience, the ...

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

small cell lung cancer (ES-SCLC): real world response ... The median overall survival (mOS) for all evaluable patients was 7.7 months, and the median duration of treatment (mDoT) was 4.3 months. At data ...

4. patlynk.com patlynk.com/trial/NCT07153055

Lurbinectedin and Osimertinib for Transformed Small Cell ... This study investigates a new treatment combination for patients with a specific type of lung cancer known as transformed small cell lung cancer.

5. researchgate.net researchgate.net/publication/388966969_Combination_of_Lurbinectedin_and_Osimertinib_for_Treatment_of_EGFR_Mutated_Transformed_Small_Cell_Lung_Cancer_A_Brief_Report/download

(PDF) Combination of Lurbinectedin and Osimertinib for ... Results A total of 312 patients were included. Lurbinectedin was delivered as second-line therapy in 138 (44%) patients. Grade 3-4 treatment- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12052803/

Combination of Lurbinectedin and Osimertinib for ... In our study, the safety profile of the lurbinectedin and osimertinib combination was predictable. All three patients experienced myelotoxicity but none of them ...

7. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/imj.16348

Lurbinectedin in small cell lung cancer: real‐world ... From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8–2.9) and OS was 4.5 months (95% CI: 3.5–7.2). From SCLC diagnosis, the ...

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.932105/full

Lurbinectedin in small cell lung cancer Lurbinectedin was approved by the Food and Drug Administration as second line for SCLC patients in progression on or after platinum-based therapy.

9. cancernetwork.com cancernetwork.com/view/real-world-lurbinectedin-exhibits-safety-and-modest-efficacy-in-es-sclc

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 ...