Lurbinectedin +/- Irinotecan for Small Cell Lung Cancer

Not currently recruiting at 276 trial locations

Overseen By Mónica Insa

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: PharmaMar

Must not be taking: Topoisomerase inhibitors

Disqualifiers: CNS metastases, Heart disease, Liver disease, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 39 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for individuals with small cell lung cancer (SCLC) who did not respond well to initial platinum-based chemotherapy. Researchers are testing two experimental treatments: one with lurbinectedin alone and another combining lurbinectedin with irinotecan. These treatments are compared against standard options, irinotecan or topotecan. Individuals who previously received platinum-based chemotherapy and have stable or treated brain metastases may be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatments.

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

The trial protocol does not specify if you need to stop your current medications. However, you must have at least three weeks since your last antineoplastic treatment and recover from any adverse events to grade ≤ 1. It's best to discuss your current medications with the trial team.

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, you must have at least three weeks since your last cancer treatment and recover from any side effects before starting the trial.

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

A previous study found lurbinectedin to be safe for patients with extensive-stage small cell lung cancer (SCLC). Patients tolerated it well when used alone, even after trying other treatments.

Research on the combination of lurbinectedin and irinotecan shows it is safe and manageable for patients with a poor outlook. While side effects may occur, they are not severe enough to halt treatment. The combination also yielded good results for those with high-risk SCLC, with many patients responding well.

Overall, both lurbinectedin alone and its combination with irinotecan appear to be safe options for treating SCLC, based on the available evidence. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for small cell lung cancer because they offer new ways to tackle the disease. Lurbinectedin is unique because it interferes with cancer cell DNA, stopping them from growing and spreading. When combined with Irinotecan, which works by disrupting cancer cell division, they form a powerful duo that could offer better outcomes than current treatments like Topotecan. This combination has the potential to enhance effectiveness and provide new hope for patients who have limited options.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research has shown that lurbinectedin, as a second treatment option for small cell lung cancer (SCLC), yields promising results. In studies, patients taking lurbinectedin lived an average of 7.7 months. It proved effective and safe, even for those who had already tried other treatments. In this trial, some participants will receive lurbinectedin alone, while others will receive a combination of lurbinectedin and irinotecan. When combined with irinotecan, lurbinectedin demonstrated strong cancer-fighting effects and remained safe to use. This combination was particularly beneficial for patients with poor outlooks from other treatments. Overall, these findings suggest that using lurbinectedin alone or with irinotecan could benefit SCLC treatment. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

Adults with small-cell lung cancer who've had one prior platinum-based chemotherapy can join this trial. They must have good organ function, no recent serious heart issues or uncontrolled infections, and cannot be pregnant or breastfeeding. Participants need to agree to use effective contraception and should not have been treated with certain drugs like lurbinectedin before.

Inclusion Criteria

Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN

Albumin ≥ 3.0 g/dL

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x upper limit of normal (ULN)

Exclusion Criteria

I haven't had serious heart issues like a heart attack or unstable angina in the past year.

I have a heart rhythm problem that needs treatment.

I have a chronic liver condition that needs treatment and haven't taken hepatitis antiviral drugs in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either lurbinectedin as a single agent, lurbinectedin in combination with irinotecan, or investigator's choice of topotecan or irinotecan

39 months

Every 3 weeks (q3wk) for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Irinotecan
• Lurbinectedin
• Topotecan

Trial Overview The LAGOON trial is testing the effectiveness of Lurbinectedin alone (Group A) or combined with Irinotecan (Group B), compared to the standard treatment choice of Topotecan or Irinotecan (Group C). This phase III study randomly assigns patients to these groups in an open-label setting.

How Is the Trial Designed?

Group I: Lurbinectedin plus Irinotecan Experimental Treatment 2 Interventions

Patients will consecutively receive the following q3wk (every three weeks = one treatment cycle): * Irinotecan (Day 1 and Day 8) * Lurbinectedin (Day 1)

Group II: Lurbinectedin Experimental Treatment 1 Intervention

Patients will consecutively receive lurbinectedin on Day 1 q3wk (every three weeks = one treatment cycle)

Group III: Control arm Active Control 2 Interventions

Best Investigator's choice prior to randomization between: * Irinotecan on Day 1 q3wk * Topotecan on Days 1-5 q3wk

Irinotecan is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Camptosar for:

• Colorectal cancer

Approved in European Union as Irinotecan for:

• Colorectal cancer

Approved in Japan as Topotecin for:

• Colorectal cancer
• Small cell lung cancer

Approved in Canada as Irinotecan for:

• Colorectal cancer

Who Is Running the Clinical Trial?

PharmaMar

Lead Sponsor

Trials

93

Recruited

11,800+

José María Fernández de Sousa-Faro

PharmaMar

Chief Executive Officer since 1986

PhD in Biochemistry, Complutense University of Madrid

Carmen Cuevas Marchante

PharmaMar

Chief Medical Officer since 2002

MD, University of Navarra

Published Research Related to This Trial

A phase I study found that alternating weekly therapy with irinotecan/cisplatin and etoposide/cisplatin was well-tolerated by patients with small-cell lung cancer, indicating a favorable safety profile for this treatment regimen.

The combination of these drugs demonstrated significant antitumor activity, suggesting a potential clinical advantage for using this approach as a first-line therapy in small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-dense therapy with a novel irinotecan regimen for small-cell lung cancer. Johnson, FM., Kurie, JM., Peeples, BO., et al.[2018]

Irinotecan, when combined with cisplatin, significantly improves survival rates in previously untreated patients with extensive-stage small-cell lung cancer, showing a median progression-free survival of 6.9 months compared to 4.8 months with standard treatment (etoposide/cisplatin).

The combination therapy also resulted in a median overall survival of 12.8 months versus 9.4 months for the standard treatment, indicating that irinotecan could be a promising new option for enhancing treatment outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan plus cisplatin in small-cell lung cancer. Sandler, A.[2018]

The maximum tolerated dose (MTD) of irinotecan hydrochloride (CPT-11) in combination with etoposide for patients with refractory advanced lung cancer was determined to be 40 mg/m2, but this regimen was associated with significant toxicity, including one treatment-related death due to pulmonary toxicity.

Out of the nine patients studied, only two achieved a partial response, indicating that while there may be some therapeutic efficacy, the treatment's safety profile raises concerns, particularly regarding pulmonary complications in patients with a history of cytotoxic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of a weekly infusion of irinotecan hydrochloride (CPT-11) and a 14-day continuous infusion of etoposide in patients with lung cancer: JCOG trial 9408. Fujishiro, M., Shinkai, T., Fukuda, M., et al.[2019]

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 study of 25 patients with refractory or relapsed small-cell lung cancer (SCLC), the combination of irinotecan (CPT-11) and etoposide resulted in a high overall response rate of 71%, with 14 partial responses and 3 complete responses, indicating its potential efficacy as a treatment option.

The treatment was associated with significant toxicities, including severe myelosuppression (56% experienced grade 3 to 4 neutropenia), highlighting the need for careful monitoring and management of side effects, but it still shows promise for further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of irinotecan and etoposide for treatment of refractory or relapsed small-cell lung cancer. Masuda, N., Matsui, K., Negoro, S., et al.[2018]

Irinotecan, a semisynthetic version of camptothecin, has shown promising activity in treating lung cancer, which has seen stagnant survival rates over the past 20 years.

The article reviews the mechanism of action and development history of irinotecan, highlighting its potential as a new treatment option for lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of irinotecan in lung cancer. Fukuoka, M.[2018]

Irinotecan (CPT-11) has demonstrated a broad range of antitumor activity across various cancer types, including lymphoma, leukemia, and several solid tumors, although most studies have focused on colorectal and gastrointestinal cancers.

Preliminary results indicate that irinotecan shows modest but reproducible activity in multiple cancers, suggesting the need for further well-designed clinical trials to better understand its efficacy and optimal use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. Rosen, LS.[2018]

Belotecan showed a higher objective response rate (33%) compared to topotecan (21%) and a significantly longer median overall survival (13.2 months vs. 8.2 months), suggesting it may be a more effective treatment for sensitive-relapsed small-cell lung cancer (SCLC).

Patients receiving belotecan also had a higher completion rate of treatment cycles (53% vs. 35%), indicating better tolerability and potential for improved patient adherence compared to topotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised phase 2b study comparing the efficacy and safety of belotecan vs. topotecan as monotherapy for sensitive-relapsed small-cell lung cancer. Kang, JH., Lee, KH., Kim, DW., et al.[2021]

Citations

1. 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 ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e20128

Lurbinectedin for small cell lung cancer (SCLC): Response ... This study aimed to analyze line-dependent outcomes and response patterns of lurbinectedin in SCLC patients. Methods: In this retrospective ...

3. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-lurbinectedin-combination-atezolizumab-or-atezolizumab-and-hyaluronidase-tqjs-extensive

FDA approves lurbinectedin in combination with ... FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925003776

Outcome and safety of lurbinectedin as compassionate use ... Compassionate use of lurbinectedin in second or further lines is effective and safe for ES-SCLC. •. Worse outcomes were observed with PS ≥ 2 ...

5. lungcancerjournal.info lungcancerjournal.info/article/S0169-5002(25)00490-8/fulltext

small cell lung cancer (ES-SCLC): real world response ... Lurbinectedin was given as second-line therapy in 39 patients (66.1 %) and as third-line or beyond in 20 patients (33.9 %). The overall response ...

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

Outcome and safety of lurbinectedin as compassionate use ... Lurbinectedin represents a therapeutic option as compassionate use in patients with ES-SCLC, especially in those with a long CFI.

7. jto.org jto.org/article/S1556-0864(23)01471-5/fulltext

P2.17-02 EFfectiveness and Safety Profile of Lurbinectedin ... In this RW study, the safety and effectiveness outcomes of lurbinectedin in 2L SCLC were generally consistent with those seen in the phase 2 basket trial ( ...

8. 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 ...