Lurbinectedin monotherapy (PM1183)

Background

Phase 2, single-arm, open-label basket trial; 26 hospitals across 6 European countries + USA. Relapsed SCLC after one prior platinum-based line. N=105. ECOG ≤2, measurable disease, no brain metastases.

Results

Interventions and follow up: Treatment: lurbinectedin 3.2 mg/m² IV 1-h infusion q3wk until progression or unacceptable toxicity (n=105).
Primary endpoint: investigator-assessed ORR (RECIST 1.1).
mFollow up: 17.1 mo (IQR 6.5–25.3).
Results: ORR (investigator): 35.2%, 95% CI 26.2–45.2 (37/105).
mPFS: NR.
mOS: NR.

Adverse events

Grade 3-4 (any causality): neutropenia 46%, leucopenia 29%, anaemia 9%, thrombocytopenia 7%.
Serious treatment-related: 10%; neutropenia and febrile neutropenia most common (5% each).
Deaths: no treatment-related deaths.

Conclusions

Lurbinectedin monotherapy was active in second-line SCLC (ORR 35%) with a manageable, mainly haematologic safety profile, offering an option for a population with few alternatives. Findings supported accelerated FDA approval and further development.

Key Limitations

Single-arm phase 2, no comparator, so efficacy cannot be benchmarked against topotecan or best supportive care. Endpoint was investigator-assessed response, not independently reviewed survival; activity heterogeneous by chemotherapy-free interval (sensitive vs resistant relapse). Brain metastases and ECOG >2 excluded. Confirmatory ATLANTIS phase 3 (lurbi + doxorubicin) later missed its OS endpoint, tempering the accelerated-approval signal.

Clinical Context

Basis for 2020 FDA accelerated approval of single-agent lurbinectedin in relapsed SCLC. Most useful in platinum-sensitive relapse, with lower response in resistant disease. ESMO/ASCO recognize it among second-line options alongside topotecan; the failed confirmatory ATLANTIS trial keeps its long-term place under discussion. The agent has since moved into first-line maintenance (IMforte). Hematologic monitoring and growth-factor support are key.