Zepzelca (lurbinectedin) / Boryung Group, PharmaMar, Jazz, Luye Group, Key Oncologics, Specialised Therap, Merck (MSD) - LARVOL DELTA

Real-world effectiveness of lurbinectedin in extensive stage small cell lung cancer (ES-SCLC). (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Lurbinectedin for small cell lung cancer (SCLC): Response patterns and survival outcomes by line of therapy. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Lurbinectedin with immunotherapy in extensive-stage small cell lung cancer: Current insights and future prospects—A systematic review. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Review • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Evaluation of the combination of lurbinectedin and atezolizumab in a humanized mouse model. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Preclinical

Early Access Program in oncology: Retrospective study at a Portuguese hospital (ECOP 2024) - "During the study period were submitted 163 EAP requests for abiraterone, amivantamab, bevacizumab, durvalumab, encorafenib, enfortumab, everolimus, erdafitinib, lenvatinib, lurbinectedin, niraparib, nivolumab, olaparib, pembrolizumab, pertuzumab, ramucirumab, sacituzumab govitecan, selpercatinib, trifluridine/tipiracil, trametinib+dabrafenib, trastuzumab-deruxtecan and tucatinib. Conclusion Most cases correspond to metastatic disease, EAPs facilitate timely access to innovative therapies for patients with high unmet medical needs. The majority of situations were financed, which confirms the importance of EAPs in an era where oncology is constantly innovating."

Retrospective data • Gastrointestinal Disorder • Oncology

Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): Primary results of the phase 3 IMforte trial. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT05091567 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Safety and efficacy of lurbinectedin plus atezolizumab as second-line treatment for advanced small-cell lung cancer: Results of the 2SMALL phase 1/2 study (NCT04253145). (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT04253145 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P1/2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Pan-inhibition of super-enhancer-driven oncogenic transcription by novel synthetic ecteinascidins yields potent anti-cancer activity (AACR 2025) - "Mechanistically, our extensive RNA-seq and chem-map assays reveal that synthetic ecteinascidins significantly suppress SE-mediated oncogene expression in melanoma cells by directly binding to and inhibiting the promoters of genes encoding ubiquitous transcription factors and coactivators that are highly enriched at oncogenic SE sites. Overall, our study provides the first evidence that the clinically approved drug, lurbinectedin, as well as its derivatives, can target and disrupt SE-dependent oncogenes, highlighting their potential as therapeutic options for cancers with transcriptionally heterogeneous landscapes where conventional therapies face significant challenges."

Cutaneous Melanoma • Lung Cancer • Melanoma • Oncology • Small Cell Lung Cancer • Solid Tumor • BRD4 • CDK7

Jazz Pharmaceuticals Showcases Transformative Data at ASCO 2025, Highlighting Advances in Small Cell Lung Cancer, HER2+ Gastroesophageal Cancer and Diffuse Glioma (PRNewswire) - "Key presentations include: (i) An oral abstract of the Phase 3 IMforte trial, which showed statistically significant and clinically meaningful survival benefit (progression-free survival (PFS) and overall survival (OS) for the combination of Zepzelca and atezolizumab (Tecentriq) for extensive-stage small cell lung cancer (ES-SCLC) patients receiving treatment in the first-line maintenance setting; (ii) A rapid oral abstract of four-year follow-up data, including new OS and translational biomarker data, from an ongoing Phase 2 trial of Ziihera in combination with chemotherapy for the first-line treatment of HER2-positive advanced or metastatic gastroesophageal adenocarcinoma (mGEA); (iii) An oral abstract of efficacy and safety data from a Phase 2 trial of dordaviprone (ONC201), from the recently completed Chimerix acquisition, in prospective clinical trials of adult and pediatric recurrent H3 K27M-mutant diffuse glioma patients."

Clinical data • Gastroesophageal Junction Adenocarcinoma • Glioma • Small Cell Lung Cancer

Small Cell Lung Cancer: A Review. (PubMed, JAMA) - "First-line treatment for ES-SCLC is combined treatment with platinum-etoposide chemotherapy and immunotherapy with the programmed cell death 1 ligand 1 (PD-L1) inhibitors durvalumab or atezolizumab followed by maintenance immunotherapy until disease progression or toxicity...Second-line therapy for patients with ES-SCLC includes the DNA-alkylating agent lurbinectedin (35% overall response rate; median progression-free survival, 3.7 months) and a bispecific T-cell engager against delta-like ligand 3, tarlatamab (40% overall response rate; median progression-free survival, 4.9 months)...First-line treatment for LS-SCLC is radiation targeting the tumor given concurrently with chemotherapy and followed by consolidation immunotherapy. For ES-SCLC, first-line treatment is chemotherapy and immunotherapy followed by maintenance immunotherapy."

Journal • Cough • Endocrine Cancer • Lung Cancer • Musculoskeletal Pain • Neuroendocrine Tumor • Oncology • Pain • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor

Novel EGFR x cMET bispecific ADC GQ1033 and DLL3-ADC GQ1030 demonstrated promising therapeutic efficacy in preclinical studies (AACR 2025) - "Using the platforms, we created a broad ADC library targeting EGFR x cMET and DLL3, combining antibodies with various formats, different linkers, and payloads like MMAE, Eribulin, Exatecan, Lurbinectedin, and TopoIx...In an osimertinib-resistant NSCLC PDX trial, involving ~10 models with diverse EGFR/cMET expression levels, GQ1033 demonstrated robust antitumor activity with an overall ORR of ~70%... GQ1033 and GQ1030, developed through high-throughput screening leveraging our iGDC™ and iLDC™ platforms, have demonstrated encouraging efficacy in preclinical studies, suggesting a broader therapeutic index. These next-gen ADCs hold potential as innovative treatments for lung cancers."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • DLL3 • EGFR

Healthcare Resource Utilization (HCRU), Costs, and Outcomes Among Patients With Extensive-Stage (ES) Small Cell Lung Cancer (SCLC) in the United States: A Retrospective, Real-World Analysis of Administrative Claims Data (ISPOR 2025) - "Patients with lung cancer were included if they had a diagnosis of metastatic disease and initiated treatment indicative of ES‑SCLC (any first-, second-, or third-line regimen containing carboplatin/cisplatin plus etoposide/irinotecan, or lurbinectedin) between January 1, 2018 and December 31, 2022 (Medicare) or July 31, 2023 (MORE2). These results highlight the substantial financial burden and poor outcomes among patients with ES-SCLC throughout the treatment journey."

HEOR • Real-world • Real-world evidence • Retrospective data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

EMERGE 402: To Assess the Effectiveness and Safety of Zepzelca in Adult Patients With Extensive Stage Small Cell Lung Cancer (SCLC) (clinicaltrials.gov) - P=N/A | N=272 | Active, not recruiting | Sponsor: Jazz Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Jun 2030 ➔ Jun 2025 | Trial primary completion date: Jun 2030 ➔ Jun 2025

Enrollment closed • Real-world evidence • Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Real-World Treatment Patterns and Outcomes in Patients With Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Treated With First-Line Platinum-Based Chemotherapy (PBC) and =2 Subsequent Lines of Therapy in the United States (ISPOR 2025) - "The most common third-line therapies were lurbinectedin monotherapy (received by 21.8% of patients); topoisomerase I inhibitor monotherapy (21.8%); chemotherapy other than platinum-based agents, topoisomerase inhibitors, and lurbinectedin (15.7%); and PD‑(L)1-‍inhibitor monotherapy (13.1%)... This study demonstrates that there is no clear standard of care among patients with ES-SCLC receiving third‑line therapy. Treatment duration is short, and outcomes, including overall survival, are poor, highlighting the substantial disease burden and need for novel treatment options in this patient population."

Clinical • HEOR • Real-world • Real-world evidence • Lung Cancer • Oncology • Primary Biliary Cholangitis • Small Cell Lung Cancer • Solid Tumor

Preclinical analysis of ONC206 and ONC212 with lurbinectedin in pancreatic cancer (AACR 2025) - "Our group recently described lurbinectedin's potency as both a single agent and combinatorial agent with irinotecan and 5-fluorouracil in pancreatic cancer cell lines. Future studies will analyze whether a combination of lurbinectedin and ONC212 or lurbinectedin and ONC206, another imipridone and chemical analogue of ONC201, proves more efficient at killing pancreatic tumor cells in vitro. Our results are developing insights into novel combinatorial therapeutic regimens while investigating the molecular mechanisms underlying synergism."

Preclinical • Lung Cancer • Oncology • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor

A phase II study of lurbinectedin with or without avelumab in small cell carcinoma of the bladder (laser)-design and rationale. (PubMed, Future Oncol) - P2 | "Treatment regimens are drawn from the small cell lung cancer (SCLC) literature, with platinum and etoposide commonly used in the first-line setting. Immune checkpoint inhibitors have also been approved for SCLC, improving survival when added to chemotherapy. This article describes the design and rationale behind LASER, an open-label phase II trial of lurbinectedin with or without avelumab.Clinical trial registration: NCT06228066 (ClinicalTrial.gov)."

Journal • P2 data • Bladder Cancer • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

IMforte: A Phase III, Open-Label Study of Maintenance Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab in Participants With Extensive-Stage Small-Cell Lung Cancer (clinicaltrials.gov) - P3 | N=660 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Mar 2026 ➔ Aug 2026

Trial completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

CYP3A Genotype Is Associated With Variability in the Exposure and Clearance of the Novel Oncogenic Transcription Inhibitor Lurbinectedin. (PubMed, Clin Transl Sci) - "A strong additive association between CYP3A4 and CYP3A5 genotypes (informed as a CYP3A activity score [AS] variable) and lurbinectedin clearance (CL) and exposure was confirmed, for example, patients with an AS of 3, 2, or 1 showed a 2.3-, 1.6-, and 1.5-fold higher total lurbinectedin CL compared to those with an AS of 0 and 2.3-, 1.8-, and 1.6-fold higher unbound lurbinectedin CL. In conclusion, preemptive CYP3A genotyping may offer a valuable approach for personalizing treatment with lurbinectedin in cancer patients."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ABCB1 • CYP3A4 • CYP3A5 • FOXA3 • NR5A2

Patient Characteristics and Treatment Patterns in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (ISPOR 2025) - "After 1L therapy, subsequent options include lurbinectedin, topotecan, platinum rechallenge (PR), and tarlatamab (since 2024). ES-SCLC patients receiving 1Lm and subsequent therapy tend to be younger and healthier than the average patients receiving 1L treatment. Lurbinectedin was the most common 2L and 3L treatment. Reasons for not proceeding with treatment intensification in 1L and 1Lm should be further investigated."

Clinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Protocol to co-culture SCLC cells with human CD8+ T cells to measure tumor cell killing and T cell activation. (PubMed, STAR Protoc) - "Here, we present a protocol to assess T cell activation and the ability of lurbinectedin to enhance anti-tumor responses using in vitro co-cultures of SCLC cells and human CD8 T cells...This protocol provides a platform to study anti-tumor T cell responses and develop new SCLC therapies. For complete details on the use and execution of the protocol, please refer to Chakraborty et al.1."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Unmet Needs in Maintenance Therapy for Extensive Stage Small Cell Lung Cancer. (PubMed, Clin Lung Cancer) - "In this review, we describe the rationale for maintenance therapy approaches in ES-SCLC and summarize the existing data on chemotherapy, ICIs, and other agents in the first-line maintenance setting. Predictive biomarkers, SCLC subtypes, and new therapeutics in development are discussed including lurbinectedin, antibody-drug conjugates, and T-cell engager molecules."

IO biomarker • Journal • Developmental Disorders • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

PharmaMar signs a new licensing, development and commercialization agreement with Merck for lurbinectedin in Japan (Pharmamar Press Release) - "PharmaMar...and Merck...announced an exclusive licensing agreement for the development and commercialization of Zepzelca (lurbinectedin), a novel transcription inhibitor for the treatment of small cell lung cancer (SCLC), in Japan. Under the terms of the agreement, PharmaMar will receive an upfront payment of €22 million. PharmaMar is entitled to tiered double digit royalties on net sales, and various clinical, regulatory, and sales based milestones totalling up to an additional €31 million. PharmaMar will supply Merck with lurbinectedin for clinical and commercial use in Japan."

Licensing / partnership • Small Cell Lung Cancer

The novel transcriptional inhibitor ecubectedin demonstrates strong antitumor activity in patient-derived xenograft models of soft tissue sarcoma (AACR 2025) - "Doxorubicin (DOX)-based chemotherapy is standard of care for advanced/metastatic disease, despite low response rates and poor disease control...Mice were randomized to 5 experimental groups and treated by tail vein injection once weekly: 1) vehicle (VEH) (5% dextrose) 5 mL/kg; 2) DOX 5 mg/kg; 3) trabectedin (TRA) 0.15 mg/kg; 4) lurbinectedin (LUR) 0.18mg/kg; 5) ECU 1.2 mg/kg... ECU has antitumor effects in PDX models of STS, with the most prominent activity seen in STS134. Next step includes investigating the role of DNA repair mechanisms in response to ECU treatment."

Preclinical • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Lurbinectedin/Irinotecan as a new therapeutic combination for small cell lung cancer (AACR 2025) - "Short term treatment of PDX models, as well as 3D cultures of organoids (PDXDO) and spheroids (CDXDS) and 2D cultures of SCLC cell lines, helped us determine that the treatment causes elevated levels of DNA Damage, a blockade in DNA Replication, and finally apoptosis. The results from this study highlight the relevance of the combination of these two already approved drugs in the treatment of SCLC."

Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Lurbinectedin synergizes with selinexor by inhibiting DNA damage repair and enhancing immune cell infiltration in neuroendocrine lung and prostate tumors (AACR 2025) - "Furthermore, treatment with lurbinectedin or the combination, enhanced the infiltration of T cells, monocytes, and macrophages into the tumor. In summary, selinexor and lurbinectedin is a promising strategy for targeting NE tumors."

Immune cell • IO biomarker • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • CHEK1 • CHEK2 • IFNG • MLH1 • MYC • PTPRC • RB1 • STING • TP53 • XPO1