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

Evaluation of the Appropriateness, Efficacy, and Safety of Lurbinectedin in Patients with Metastatic Small Cell Lung Cancer (ASHP 2025) - No abstract available

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

Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small-cell lung cancer (ES-SCLC): IMforte Asia subgroup results (ESMO Asia 2025) - P3 | "We report exploratory results from pts enrolled in Asia. Eligible pts with ES-SCLC without progressive disease (PD) after 1L induction tx with atezo, carboplatin, and etoposide were randomised 1:1 to maintenance tx IV q3w with lurbi 3.2 mg/m2 (with G-CSF prophylaxis) + atezo 1200 mg or atezo alone until PD or unacceptable toxicity. In pts from Asia, 1L maintenance tx of ES-SCLC with lurbi + atezo improved PFS and OS vs atezo, consistent with data from the global study population. Although TRAEs occurred more frequently in the lurbi + atezo arm, these were consistent with the known safety profile of both drugs; discontinuation due to toxicity was infrequent."

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

SEZanne: A Study to Evaluate the Optimal Dose, Adverse Events and Change in Disease Activity of Intravenous ABBV-706 in Combination With Atezolizumab Versus Standard of Care as First-Line Treatment in Adult Participants With Previously Untreated Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting | Phase classification: P2/3 ➔ P2

Adverse events • Enrollment open • Phase classification • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Experts Unpack the Most Notable NCCN Guideline Changes Heading Into 2026 (OncLive) - "'[During 2025], adjuvant therapy regimens from the [phase 3] ATOMIC trial [NCT02912559]—FOLFOX or CAPEOX in combination with atezolizumab—were added in stage III dMMR/MSI-H colon cancer. This change represents the addition of checkpoint inhibitor therapies at earlier points of the patient journey.' Al B. Benson, III, MD...said in a statement to OncLive."

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INVESTIGATING THE SAFETY AND EFFICACY OF LURBINECTEDIN WITH IPILIMUMAB AND NIVOLUMAB FOR ADVANCED SOFT TISSUE SARCOMA: LINNOVATE PHASE 1/2 STUDY (NCT05876715) (CTOS 2025) - P1/2 | "Therefore, immune checkpoint inhibitors (ICIs) such as ipilimumab and nivolumab, which enhance sustained T-cell activation by suppressing regulatory T cells, are most effective when administered as first-line therapy in combination with lurbinectedin—a synthetic analog of the marine alkaloid trabectedin—that not only induces apoptosis in cancer cells and exposes tumor neoantigens for immune recognition but also depletes tumor-associated macrophages, thereby restoring immune surveillance and potentially enhancing the efficacy of ICIs. The observed 28% BORR and 100% CBR support the continuation of the phase 2 portion of the study, with manageable toxicity."

Clinical • Metastases • P1/2 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): Exploratory results of biomarker, updated efficacy and safety analyses from the phase III IMforte trial (ESMO-IO 2025) - P3 | "We report exploratory biomarker and exploratory updated efficacy and safety results.Methods Pts without progressive disease (PD) after 1L induction tx (atezo + carboplatin + etoposide) were randomised 1:1 to IV maintenance tx q3w with lurbi 3.2 mg/m2 + atezo 1200 mg or atezo until PD or unacceptable toxicity. With longer FU, clinically meaningful INV-PFS and OS improvements were maintained with lurbi + atezo vs atezo. Safety remained consistent with the known atezo and lurbi profiles.Clinical trial identification NCT05091567.Editorial acknowledgement Medical writing assistance for this abstract was provided by Nimisha H. Bhoola, PhD, of Nucleus Global, an Inizio Company, and funded by F. Hoffmann-La Roche Ltd.Legal entity responsible for the study F. Hoffmann-La Roche Ltd and Jazz Pharmaceuticals plc."

Biomarker • Clinical • IO biomarker • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • PD-L1

Safety and Efficacy of Radiotherapy Combined With Immunochemotherapy in Pre-treated SCLC Patients With Liver Metastases (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Sichuan University

New P2 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

IDENTIFICATION OF A DNA REPAIR INHIBITOR FOR THE COMBINATION WITH LURBINECTEDIN AND RADIOTHERAPY IN SARCOMA CELL LINES (CTOS 2025) - "Objective: Improved multimodal treatment could optimize therapeutic outcomes for sarcoma patients. Our preclinical data suggest that the combination of LU with RT has no sensitizing effect compared to LU treatment alone in sarcoma cell lines. However, combining LU and IR with DNA repair inhibitors such as the ATRi VE-822 is a promising way to improve sarcoma treatment."

Preclinical • Fibrosarcoma • Liposarcoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Synovial Sarcoma • ANXA5

Swiss medical authority approves PharmaMar’s Zepzelca (lurbinectedin) and Atezolizumab (Tecentriq) combination as first-line maintenance therapy for extensive-stage small cell lung cancer (Pharmamar Press Release) - "The Swissmedic approval is based on results from the Phase 3 IMforte trial, which showed that the lurbinectedin and atezolizumab combination reduced the risk of disease progression or death by 46% and the risk of death by 27%, compared to atezolizumab maintenance therapy alone."

Approval • Small Cell Lung Cancer

EFFECTIVENESS OF LURBINECTEDIN PLUS IRINOTECAN IN PRECLINICAL MODEL OF DESMOPLASTIC SMALL ROUND CELL TUMOR (CTOS 2025) - "We demonstrated the effectiveness of the combination trabectedin plus irinotecan in a PDX model of DSRCT. Lurbinectedin and irinotecan exhibit potent antiproliferative activity in DSRCT models. These results lead to the design of a phase II study of lurbinectedin and irinotecan in adult and young adult patients with advanced DSRCT (EU 2024-519261-21-00). Further molecular studies on the effect of drugs on EWS::WT1 modulation both in vitro and in vivo are ongoing."

Preclinical • Oncology • Soft Tissue Sarcoma • WT1

THE NOVEL TRANSCRIPTIONAL INHIBITORS ECUBECTEDIN AND PM54 DEMONSTRATE ANTITUMOR ACTIVITY IN PATIENT-DERIVED XENOGRAFT MODELS OF SOFT TISSUE SARCOMA (CTOS 2025) - "The novel compounds ECU and PM54 consistently showed the strongest antitumor activity in the PDX models tested, achieving prolonged TV-stabilization in STS336 even after treatment cessation. In ongoing experiments we are now exploring the impact of the DNA repair capacity of the models on the antitumor effects observed with the drugs.Tumor volume change on day 16 and comparison of mitotic and apoptotic activity of respective treatment groups compared to vehicle on day 16. ↓ decrease in activity, as compared to baseline."

Preclinical • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

FDA approves lurbinectedin in combination with atezolizumab for extensive-stage small cell lung cancer. (PubMed, Oncoimmunology) - "The recent FDA approval of lurbinectedin plus atezolizumab for advanced small cell lung cancer underscores the promise of combining immunogenic cell death (ICD) inducers with PD-1/PD-L1 blockade. This synergistic strategy induces durable responses in refractory tumors and may extend immunotherapy benefits across diverse malignancies through rational ICD-checkpoint inhibitor combinations."

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

Zepzelca: Newly added patents in Orange Book (Orange Book) - Expiry on May 29, 2040

Patent • Neuroendocrine Tumor • Oncology • Solid Tumor • Thoracic Cancer

Drug screening reveals differential drug response in primary and metastatic clear cell sarcoma. (PubMed, Cancer Lett) - "Furthermore, we explored combinational treatment of lurbinectedin with selinexor. Synergistic effects were confirmed in a novel autologous co-culture model incorporating cancer-associated fibroblasts, providing a more physiologically relevant system for drug testing. This study identified promising therapeutic avenues by highlighting key vulnerabilities in CCS, considering both inter tumour heterogeneity, tumour plasticity and the stromal influence on drug response."

Journal • Oncology • Sarcoma • Solid Tumor

SEZanne: A Study to Evaluate the Optimal Dose, Adverse Events and Change in Disease Activity of Intravenous ABBV-706 in Combination With Atezolizumab Versus Standard of Care as First-Line Treatment in Adult Participants With Previously Untreated Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P2/3 | N=180 | Not yet recruiting | Sponsor: AbbVie | Trial completion date: May 2029 ➔ Sep 2031

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

Real-World Treatment Patterns and Clinical Outcomes in Patients With Extensive-Stage Small Cell Lung Cancer Treated With First-Line Platinum-Based Chemotherapy and ≥ 2 Subsequent Lines of Therapy in the United States. (PubMed, Adv Ther) - "This study demonstrated the heterogeneity of treatments after 1L PBC-containing therapy for patients with ES-SCLC, with no clear standard of care identified. In 3L, rwTTD/D, rwTTNT/D, and rwOS were short, demonstrating the substantial unmet need for novel treatments in this setting."

Clinical data • HEOR • Journal • Real-world evidence • 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) Previously Treated With First-Line (1L) Platinum-Based Chemotherapy (PBC) (ISPOR-EU 2025) - P | "In this real-world study of patients with ES-SCLC in France, 2L and 3L treatments were heterogeneous, the most common being PBC without immunotherapy. Outcomes in patients with recurrent SCLC were very poor, highlighting the need for novel treatment options."

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

Network Meta-Analysis NMA of Clinical Effectiveness of Second-Line (2L+) Treatments in Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (ISPOR-EU 2025) - "DeLLphi-304, an ongoing phase III randomized controlled trial (RCT), showed that tarlatamab offers considerable clinical benefit in head-to-head comparisons versus chemotherapies (topotecan, amrubicin, or lurbinectedin). An NMA was conducted to indirectly compare tarlatamab with existing 2L treatments, including those not evaluated in DeLLphi-304. Bayesian NMAs using fixed effects models were used to compare overall survival (OS) and progression-free survival (PFS) among treatments in the overall 2L population (tarlatamab, topotecan, cyclophosphamide + doxorubicin + vincristine [CAV], amrubicin, and irinotecan-based regimens) and the platinum-sensitive (defined as chemotherapy-free interval ≥ 90 days) subgroup (tarlatamab, topotecan, platinum rechallenge, amrubicin, and liposomal irinotecan). In the overall 2L population, tarlatamab demonstrated significant improvements in OS compared to all comparators, with hazard ratios (HRs) ranging from 0.50 (95% credible interval..."

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

Indirect Comparison of Tarlatamab vs. Chemotherapy (CTx) in Patients With Previously Treated, Platinum-Refractory, or Resistant Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (ISPOR-EU 2025) - P2, P3 | "OBJECTIVES: Tarlatamab showed considerable benefit in response, survival, and patient-reported outcomes compared to CTx (topotecan, lurbinectedin, or amrubicin) in ES-SCLC after first-line platinum-based therapy in the DeLLphi-304 trial (NCT05740566). While paclitaxel and cyclophosphamide/doxorubicin/vincristine (CAV) are treatment options for platinum-refractory or resistant ES-SCLC, there is a lack of head-to-head data comparing these treatments with tarlatamab... Tarlatamab offers significant efficacy benefit relative to paclitaxel and CAV in patients with platinum-refractory or resistant ES-SCLC in the second-line setting. These findings reinforce tarlatamab as an effective treatment option for this population."

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

Costs Associated With the Administration, Postinfusion Monitoring, and Management of Adverse Events (AEs) Related to Novel Drugs for Second-Line (2L+) Treatment of Small-Cell Lung Cancer (SCLC) (ISPOR-EU 2025) - "This analysis showed that treatment with lurbinectedin is associated with substantial cost savings in the administration, post-infusion monitoring, and adverse events management compared with tarlatamab in 2L SCLC."

Adverse events • Clinical • Anemia • Inflammation • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Business Updates:…Zepzelca (lurbinectedin) (PRNewswire) - "Net product sales decreased 8% to $79.3 million in 3Q25 compared to 3Q24."

Sales • Small Cell Lung Cancer

Place in therapy of key treatments for platinum-sensitive, relapsed, extensive-stage small cell lung cancer with a focus on lurbinectedin: a narrative review with case studies. (PubMed, Drugs Context) - "Case studies highlight objective and durable responses to second-line lurbinectedin, along with good tolerability and quality of life. Available evidence supports second-line lurbinectedin as a useful alternative to platinum rechallenge, topotecan and cyclophosphamide-doxorubicin-vincristine in patients with platinum-sensitive relapsed SCLC."

Journal • Platinum sensitive • Review • Hematological Disorders • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Increasing the efficacy of ICB by lurbinectedin mediated re-activation of tumor microenvironment in SCLC. (SITC 2025) - "By enhancing T-cell infiltration, antigen presentation, and co-stimulatory signaling, lurbinectedin may significantly improve patient responses to ICB. This study provides a strong rationale for combining lurbinectedin with ICB, offering new hope for improving clinical outcomes in patients with SCLC."

Biomarker • Clinical • IO biomarker • Tumor microenvironment • Endocrine Cancer • Lung Cancer • Neuroendocrine Carcinoma • Oncology • Small Cell Lung Cancer • Solid Tumor • CD19 • CD8 • SDC1

Palliative Radiotherapy With Lurbinectedin in Patients With Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=22 | Recruiting | Sponsor: Emory University | Trial completion date: Jul 2025 ➔ Jul 2027 | Trial primary completion date: Jul 2025 ➔ Jul 2026

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

Tarlatamab as second-line (2L) treatment for small cell lung cancer (SCLC): Outcomes by chemotherapy-free interval (CFI) and prior PD-(L)1 inhibitor use in the phase III DeLLphi-304 trial (ESMO 2025) - P3 | "Methods Patients were randomised 1:1 to tarlatamab or CTx (topotecan, lurbinectedin, or amrubicin) Post hoc analysis was conducted for prespecified subgroups based on CFI (< 90 vs ≥ 90 days) and prior anti-PD-(L)1 use (yes vs no). Additionally, in contrast to CTx, the reduced risk of death and higher ORR with tarlatamab remained consistent even in platinum-resistant disease where prognosis has been especially poor, reinforcing tarlatamab as a standard of care for 2L SCLC. Table: LBA101 CFI Tarlatamab CTx Tarlatamab CTx < 90 days ≥ 90 days Efficacy n = 109 n = 114 n = 145 n = 141 Median OS, mos 10.9 6.4 17.1 10.6 HR (95% CI) 0.60 (0.43, 0.84) 0.65 (0.45, 0.93) Median PFS, mos 3.2 2.7 4.5 4.4 HR (95% CI) 0.71 (0.54, 0.94) 0.73 (0.56, 0.95) Safety n = 107 n = 109 n = 145 n = 135 Grade ≥ 3 TRAEs, % 30 58 24 66 TRAE leading to dose interruption or reduction, % 21 50 18 59 CRS, % 59 - 54 - Prior PD-(L)1 Yes No Efficacy n = 180 n = 180 n = 74 n = 75 Median OS, mos..."

Clinical • Late-breaking abstract • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor