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

On 26 March 2026, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Zepzelca, intended for the treatment of extensive-stage small cell lung cancer (ES-SCLC). (European Medicines Agency) - "Zepzelca, in combination with atezolizumab, is indicated for the maintenance treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy with atezolizumab, carboplatin and etoposide."

CHMP • Small Cell Lung Cancer

REAL-WORLD TREATMENT PATTERNS, OUTCOMES, HCRU AND COSTS ASSOCIATED WITH PREVIOUSLY-TREATED EXTENSIVE-STAGE SCLC IN THE US FOLLOWING THE APPROVAL OF NEWER TREATMENT OPTIONS (ISPOR 2026) - "In 2L, lurbinectedin (44.7%), carboplatin + etoposide + atezolizumab (10.2%), and tarlatamab (9.8%) were most common. In 3L, lurbinectedin and tarlatamab were most common (28.3% each), followed by nivolumab or pembrolizumab (5.4% each)... Early real-world data post-tarlatamab approval show high costs and mortality. In addition, fragmented 2L/3L treatment highlights the need for novel therapies that improve clinical and economic outcomes."

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

Patterns of disease progression (PD) and efficacy associated with tumour burden from the phase III IMforte study of lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in ES-SCLC (ESMO 2025) - P3 | "Methods Eligible pts with ES-SCLC without PD after 1L induction tx with atezo, carboplatin, and etoposide were randomised 1:1 to maintenance tx q3w with lurbi 3.2 mg/m 2 + atezo 1200 mg or atezo until PD or unacceptable toxicity. Table: 2762MO Association of OS and IRF-PFS with maintenance BL tumour burden OS IRF-PFS Lurbi + atezo Atezo Lurbi + atezo Atezo Non-measurable disease only, n 67 59 67 59 Median, mo 16.4 12.2 7.3 2.8 Unstratified HR (95% CI) 0.75 (0.44, 1.28) 0.56 (0.36, 0.86) Measurable disease with baseline SOD <median, n 89 86 89 86 Median, mo 13.2 13.6 5.5 2.4 Unstratified HR (95% CI) 0.96 (0.62, 1.47) 0.58 (0.41, 0.82) Measurable disease with baseline SOD ≥median, n 86 96 86 96 Median, mo 11.7 8.6 4.2 1.6 Unstratified HR (95% CI) 0.59 (0.40, 0.86) 0.52 (0.37, 0.72) Conclusions Proportionately fewer IRF-defined PD events were observed in target/non-target lesions in the lurbi + atezo vs atezo arms. The addition of lurbi led to greater OS improvement..."

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

SEZanne: A phase II randomized, open-label, multicenter study to evaluate the optimal dose, safety, and efficacy of ABBV-706 in combination with atezolizumab (atezo) versus standard of care (SOC) in patients (pts) with previously untreated extensive-stage (ES) small cell lung cancer (SCLC) (ELCC 2026) - P2 | "Adding a PD-L1 inhibitor (atezo or durvalumab) to PCT only modestly improves survival, and novel therapies are needed...SOC includes 4 cycles of PCT (carboplatin) + etoposide + atezo followed by atezo maintenance; lurbinectedin may also be used in maintenance where locally approved...Treatment continues until progression, intolerable toxicity, or other discontinuation criteria are met. The study is enrolling."

Clinical • Combination therapy • IO biomarker • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SEZ6

Lurbinectedin plus atezolizumab vs durvalumab maintenance in ES-SCLC: A comparative clinical and economic analysis (AACR 2026) - "The IMforte combination offers superior PFS and potentially longer OS than CASPIAN's durvalimab-based regimen, but with increased bone marrow toxicity and significantly higher costs. CASPIAN's regimen is more cost-effective, making it a viable option in resource-constrained settings, and lurbenectin can be used as a following line of treatment after progression on durvalumab. The IMforte trial did not allow a crossover; hence, it is unknown if early introduction of lurbecnectin for ES-SCLC will better survival rather than when used as a subsequent line treatment."

Clinical • HEOR • Omic analysis • 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 | N=27 ➔ 180

Adverse events • Enrollment change • Trial initiation date • 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): Primary results of the phase 3 IMforte trial. (ASCO 2025) - P3 | " Tx-naive pts with ES-SCLC received standard induction tx with atezo, carboplatin, and etoposide for four 21-day cycles (q3w). IMforte met both primary endpoints of IRF-PFS and OS, demonstrating a clinically meaningful benefit with 1L maintenance tx with lurbi + atezo vs atezo in pts with ES-SCLC. Lurbi + atezo was generally well tolerated, with no new or unexpected safety signals. IMforte is the first global Phase 3 study to show PFS and OS improvement with 1L maintenance tx for ES-SCLC and supports maintenance lurbi + atezo as a new option for pts with this aggressive disease."

Clinical • P3 data • Febrile Neutropenia • Infectious Disease • Lung Cancer • Neutropenia • Oncology • Septic Shock • 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=50 | Recruiting | Sponsor: AbbVie | N=27 ➔ 50

Adverse events • Enrollment change • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

IMforte: Subsequent treatment (Tx) following first-line maintenance (1Lm) with lurbinectedin (lurbi) + atezolizumab (atezo) or atezo in extensive stage small cell lung cancer (ES-SCLC) (ELCC 2026) - P3 | "Here, we report a post hoc analysis of subsequent Tx after discontinuation of 1Lm Tx in IMforte and explore the potential impact of such Tx on OS.Methods Eligible pts with ES-SCLC who did not progress after induction with atezo, carboplatin, and etoposide were randomised 1:1 to receive lurbi (3.2 mg/m2) + atezo (1200 mg) or atezo alone every 3 weeks until unacceptable toxicity, disease progression, or withdrawal of consent...Table: 423P Subsequent Tx n (%)a Lurbi + atezo n = 242 Atezo n = 241 2L Tx 108 (45) 132 (55) Topotecan alone 20 (19) 29 (22) Platinum-based chemotherapy 39 (36) 35 (27) CAVb 12 (11) 17 (13) Lurbib 0 17 (13) Atezo alone 20 (19) 5 (4) Tarlatamab alone 1 (1) 7 (5) Irinotecan alone 4 (4) 9 (7) Other 12 (11) 13 (10) 3L Tx 32 (13) 30 (12) Topotecan alone 2 (6) 5 (17) Platinum-based chemotherapy 7 (22) 7 (23) CAVb 6 (19) 2 (7) Lurbib 0 3 (10) Tarlatamab alone 2 (6) 0 Irinotecan alone 5 (16) 4 (13) Other 10 (31) 9 (30) aOverall Tx line % calculated from..."

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

Real-world (RW) effectiveness and safety of lurbinectedin for previously treated small cell lung cancer (SCLC): Jazz EMERGE 402 (ELCC 2026) - P | "Background Lurbinectedin received accelerated approval in the US for extensive stage (ES)-SCLC that progressed on or after platinum-based therapy in 2020 based on a phase II basket trial and full approval combined with atezolizumab as first-line maintenance therapy for ES-SCLC in 2025 based on the phase III IMforte trial.Methods The phase 4, prospective, observational Jazz EMERGE 402 trial (NCT04894591) evaluated lurbinectedin for previously treated ES-SCLC in RW practice in North America. dEstimated using Kaplan-Meier methodology. Conclusions Lurbinectedin was associated with clinically meaningful effectiveness and predictable/manageable safety for previously treated ES-SCLC in a RW population, including poor-prognosis subgroups."

Clinical • Real-world • Real-world evidence • 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=27 | Recruiting | Sponsor: AbbVie

Adverse events • New P2 trial • 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, P3 | "The combination of LUR and ATZ showed promising efficacy in patients with relapsed SCLC regardless of prior exposure to immunotherapy, including those with resistance to platinum. The associated safety profile is manageable. The regimen is being evaluated in a phase III trial in the maintenance setting (IMforte trial NCT05091567)."

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

In-depth profiling of SCLC models of acquired chemoresistance reveals SLFN11-dependent antibody-drug conjugate payload sensitivity and ATR inhibitor synergy (AACR 2026) - "Drug screens were conducted to identify therapeutic vulnerabilities, including responses to unconjugated antibody-drug conjugate (ADC) payloads and targeted pathway inhibitors. Cisplatin-resistant (CR) SCLC models exhibited broad cross-resistance to clinically relevant cytotoxic drugs such as carboplatin, lurbinectedin, and topoisomerase I and II (TOP1 and TOP2) inhibitors...Importantly, inhibition of ATR with ceralasertib synergized with DNA-damaging ADC payloads, re-sensitizing SLFN11-low resistant models by increasing DNA damage and inducing apoptosis. Our findings demonstrate shared adaptive mechanisms of acquired cisplatin resistance in SCLC, including checkpoint rewiring and metabolic flexibility... Our findings demonstrate shared adaptive mechanisms of acquired cisplatin resistance in SCLC, including checkpoint rewiring and metabolic flexibility. SLFN11 was identified as a key determinant of TOP1-directed ADC efficacy. Combining ATR inhibition with DNA-damaging..."

ADC • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SLFN11 • TOP1

PharmaMar’s treatment for small cell lung cancer approved as first-line maintenance therapy in Taiwan (Pharmamar Press Release) - "This approval as a first-line maintenance therapy means that the drug is administered after the initial induction treatment for those patients who achieve stable disease or better, in order to maintain the response achieved."

Approval • Small Cell Lung Cancer

Marine-Derived Anticancer Compounds and their Clinical Status. (PubMed, Anticancer Agents Med Chem) - "Marine sources offer a wide variety of compounds, and modifying them provides researchers with new opportunities for drug development. Many marine-derived compounds have already shown strong pharmacological effects, with some even proven in clinical use. New studies suggest that marine compounds could also play an important role in anticancer drug delivery systems, making them a promising option for future treatments."

Journal • Oncology

Brief Report: Real-World Outcomes of Lurbinectedin in Veterans With Small Cell Lung Cancer. (PubMed, Clin Lung Cancer) - No abstract available

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

Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. (PubMed, N Engl J Med) - P3 | "Treatment with tarlatamab led to longer overall survival than chemotherapy among patients with small-cell lung cancer whose disease had progressed during or after platinum-based chemotherapy. (Funded by Amgen; DeLLphi-304 ClinicalTrials.gov number, NCT05740566.)."

Journal • Cough • Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • 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

Tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): Primary analysis of Ph3 DeLLphi-304. (ASCO 2025) - P3 | "The DeLLphi-304 trial showed tarlatamab significantly improved OS, PFS, and PROs, with a favorable safety and tolerability profile compared to CTx in pts with SCLC that progressed on or after initial platinum-based CTx, defining a new standard of care for these patients. Clinical Trial Information: NCT05740566; Legal entity responsible: Amgen Inc.; Funding: Amgen Inc.; Editorial acknowledgement: Medical writing support for the development of this abstract was provided by Sukanya Raghuraman, PhD, of Cactus Life Sciences, part of Cactus Communications, and was funded by Amgen Inc. MD: mean difference; NE: not estimable; wks, weeks.*Topotecan (n=185), lurbinectedin (n=47), or amrubicin (n=23).†EORTC QLQ-C30 scale.‡EORTC QLQ-LC13 scale.§Non-significant."

Clinical • Late-breaking abstract • Anemia • Cough • Lung Cancer • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor

Phase 1 trial of ZL-1310, a DLL3-targeted ADC, in patients with previously treated extensive-stage small cell lung cancer (AACR-NCI-EORTC 2025) - P1 | "All pts had prior platinum-based chemotherapy, of whom 90.4% received a prior anti-PD‑L1, 13 (12.5%) had prior lurbinectedin, and 10 (9.6%) had a prior DLL3-targeted therapy. ZL-1310 has a manageable safety profile, encouraging activity, and displayed meaningful improvements in pts with CNS disease, addressing a critical unmet need – including in those with asymptomatic, untreated brain metastases. These data support further clinical development of ZL-1310 in SCLC."

Clinical • Late-breaking abstract • P1 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Investigation of lurbinectedin-induced cytosolic DNA/RNA sensors activation and immune cell-mediated cytotoxicity in small cell lung cancer (ELCC 2026) - "Sequential treatment with cisplatin followed by lurbinectedin, with or without radiotherapy, modulated DNA damage response pathways and activated cytosolic DNA/RNA sensing mechanisms. These assays demonstrated enhanced cytotoxic activity of CD8+ T cells and natural killer (NK) cells in the presence of lurbinectedin. Overall, our data demonstrate that lurbinectedin triggers multiple immune-related pathways, including STING- and MAVS-dependent signaling, leading to increased antigen presentation and induction of immunogenic cell death.Conclusions The observed potentiation of CD8+ T-cell and NK-cell cytotoxicity provides a strong mechanistic rationale for combining lurbinectedin with immune checkpoint blockade to improve therapeutic outcomes in SCLC."

Immune cell • IO biomarker • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD8 • GAPDH

Lurbinectedin With Berzosertib, an ATR Kinase Inhibitor in Small Cell Cancers and High-Grade Neuroendocrine Cancers (clinicaltrials.gov) - P1/2 | N=37 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=120 ➔ 37 | Trial primary completion date: Aug 2026 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial primary completion date • Endocrine Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

PM54 suppresses WNT/β-catenin signaling and synergizes with chemotherapy in gastric cancer models (AACR 2026) - "Background: PM54 is a lurbinectedin analog that binds CG-rich promoter regions, inducing transcriptional blockade, DNA double-strand breaks, and S-phase arrest culminating in apoptosis...Drug interactions with 5-fluorouracil (5-FU) and cisplatin were quantified by combination index analysis... PM54 represses WNT/β-catenin signaling and enhances the efficacy of chemotherapy in gastric cancer models. These findings support its development in rational combination regimens to improve patient outcomes."

Preclinical • Gastric Cancer • Oncology • Solid Tumor

Lurbinectedin alters EWS::FLI1 binding to chromatin to poison transcription (AACR 2026) - "Lurbinectedin is a small molecule analog of the natural product trabectedin that has shown efficacy in multiple cancers including Ewing sarcoma. This modulation of EWS::FLI1 binding to chromatin occurs in both a concentration and time dependent manner. Intriguingly, the impact appears to be dependent on gene length: there is greater transcription alteration in longer genes compared to shorter genes."

Ewing Sarcoma • Oncology • Sarcoma • Solid Tumor • FLI1

PM54 targets oncogenic transcriptional networks across multiple cancer types (AACR 2026) - "Background: PM54, a synthetic ecteinascidin analog derived from lurbinectedin, binds GC-rich promoter regions to block transcription, induce DNA double-strand breaks, and trigger S-phase arrest and apoptosis... PM54 rapidly suppresses proliferative/MYC-driven programs and elicits adaptive metabolic/immune responses. Baseline transcriptional state predicts response and may guide patient selection and combination strategies."

Breast Cancer • Gastric Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • POU2F3