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

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 3 IMforte trial (ESMO-IO 2025) - No abstract available

Biomarker • Clinical • P3 data • 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) - No abstract available

Clinical • 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

Detailed safety analysis of DeLLphi-304: The first phase III study to evaluate tarlatamab versus chemotherapy for previously treated small cell lung cancer (ESMO 2025) - P3 | "Methods Pts were randomized to tarlatamab or chemotherapy (CTx: topotecan, lurbinectedin, or amrubicin). Conclusions In the DeLLphi-304 trial, tarlatamab demonstrated a predictable and manageable safety profile in 2L SCLC, with no new safety signals identified. Table: LBA100 Treatment-related adverse events TRAE Tarlatamab (n = 252) CTx (n = 244) All Grades Grade ≥3 All Grades Grade ≥3 Anemia 19.8% 2.0% 61.5% 27.9% Neutropenia 7.5% 4.4% 29.5% 22.1% Thrombocytopenia 3.2% 0.4% 23.8% 11.8% Infection 6.3% 1.2% 15.2% 8.6%"

Clinical • Late-breaking abstract • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • DLL3

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

Clinical benefit analysis of a phase I/II study using lurbinectedin combined with ipilimumab and nivolumab as first-line therapy for advanced soft tissue sarcoma (NCT05876715) (ESMO 2025) - P1/2 | "Background The efficacy of immune checkpoint inhibitors (ICIs) increases when given as first line therapy for sarcomas and may have synergistic activity with lurbinectedin, a synthetic version of the marine alkaloid trabectedin, whose plausible mechanism of action is not only to induce apoptosis in cancer cells but also to deplete growth promoting tumor-associated macrophages in the tumor microenvironment. In Phase 2, there was 1/6 CR, 1/6 PR and 4/6 SD with a 28% BORR and 100% CBR. Conclusions The data indicates that 28% BORR and 100% CBR warrant continuing the Phase 2 part of the study with manageable toxicity."

Clinical • Metastases • P1/2 data • Oncology • Sarcoma • Soft Tissue 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 | N=730 ➔ 180 | Trial completion date: Sep 2031 ➔ May 2029 | Trial primary completion date: Sep 2031 ➔ May 2029

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

Real-world treatment patterns and progression-free survival from first-line chemoimmunotherapy in patients with extensive-stage small cell lung cancer in the US (ESMO 2025) - "Most (89.5%) pts received atezolizumab-based 1L CIT...Among pts with ≥2 LOTs, most were treated with a new regimen (82.4%), most commonly lurbinectedin (37.5%) or a topoisomerase inhibitor (24.5%), while 17.6% were rechallenged with a platinum-etoposide-based regimen...Conclusions In US rw practice, pts with ES-SCLC treated with 1L CIT experience rapid disease progression and many do not receive subsequent tx, possibly due to poor clinical status or other factors. This highlights that rw prognosis for these pts remains poor, with an unmet need for novel tx options to improve their outcomes."

Clinical • HEOR • Real-world • Real-world evidence • Lung Cancer • Oncology • 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

Increasing the efficacy of immunotherapy by lurbinectedin-mediated reactivation of the tumor microenvironment in SCLC [WITHDRAWN] (ESMO 2025) - No abstract available

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

IDeate-Lung02: A Study of Ifinatamab Deruxtecan Versus Treatment of Physician's Choice in Subjects With Relapsed Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=540 | Active, not recruiting | Sponsor: Daiichi Sankyo | Recruiting ➔ Active, not recruiting

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

Efficacy of ABBV-706 as second-line treatment for patients with platinum-refractory/resistant small cell lung cancer (ESMO 2025) - P1 | "Background First-line (1L) standard of care (SOC) for extensive-stage small cell lung cancer (SCLC) includes platinum chemotherapy + etoposide (PE), with a PD-L1 inhibitor...Cross-trial comparison showed that ABBV-706 had improved efficacy (ORR, DOR, and PFS) compared with approved 2L agents lurbinectedin and topotecan...Given the antitumor effect observed in PDX models and improved outcomes in PE-resistant pts from NCT05599984, ABBV-706 has the potential to replace 1L SOC in SCLC. Table: 2777P Efficacy observed in NCT05599984 Clinical trial pts N=80 1.8 mg/kg n=41 2.5 mg/kg n=39 CTFI <30 days n=19 CTFI <90 days n=41 ORR, % (n/N) 56 (23/41) 59 (23/39) 53 (10/19) 59 (24/41) mDOR, months [95% CI] 6.2 [4.2, NE] 4.4 [3.5, 6.9] 5.7 [2.8, NE] 5.6 [3.2, 6.9] Median PFS-706, months [95% CI] 6.8 [4.0, 8.2] 5.6 [4.4, 7.0] 5.7 [3.9, 7.5] 5.7 [4.2, 7.0] Median PFS-L1, months [95% CI] 6.1 [4.6, 8.8] 6.5 [4.8, 8.4] 4.0 [3.0, 6.0] 4.4 [4.2, 5.5] CTFI, chemotherapy-free..."

Clinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • SEZ6

Increasing the efficacy of ICB by lurbinectedin mediated re-activation of tumor microenvironment in SCLC. (SITC 2025) - "At that time, full Regular and YIA abstracts will be published as a preprint supplement in the Journal for ImmunoTherapy of Cancer (JITC). This includes content within the original abstract submitted."

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

Real-world third-line treatment patterns and outcomes for recurrent or extensive stage small cell lung cancer (SCLC) in the Canadian small cell lung cancer database (CASCADE) (ESMO 2025) - "3L included CAV 28%, camptothecin derivatives 23%, platinum doublet 21%, immunotherapy 3%, lurbinectedin 2%, other 23%. Patients eligible for 3L therapies such as tarlatamab are limited and, by reaching 3L, demonstrate a different disease trajectory than most SCLC patients. Legal entity responsible for the study The authors."

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

Real-world (rw) treatment (tx) patterns and outcomes in French patients (pts) with extensive stage small cell lung cancer (ES-SCLC) treated in second-line (2L) (ESMO 2025) - "For 2L therapies, 33% used platinum CTx + etoposide (PE rechallenge), 14% used topotecan, 13% used cyclophosphamide, doxorubicin, and vincristine, 12% used lurbinectedin through compassionate access, 4% used PE + IO, and 23% used other CTx. Survival was consistently poor across all 2L groups with modestly higher median OS in prognosis in the PS group (Table). Table: 2787P Survival outcomes from initiation of 2L tx N rwOS rwPFS Median 95%CI Median 95%CI Overall 270 5.4 4.7 - 6.5 3.1 2.8 - 3.5 PS 133 7.8 6.5 - 9.9 4.4 3.9 - 5.2 PR 136 4.0 3.3 - 5.0 2.2 2.0 - 2.8 1L IO naive 95 4.7 3.9 - 6.5 2.8 2.5 - 3.7 1L IO exposed 175 5.8 5.0 - 7.0 3.2 2.8 - 3.8 Conclusions Despite available 2L txs for ES-SCLC in France, prognosis remains poor, highlighting the urgent need for more effective txs to improve outcomes."

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

Intracranial activity of ifinatamab deruxtecan (I DXd) in patients (pts) with extensive-stage (ES) small cell lung cancer (SCLC) and baseline (BL) brain metastases (BM): Primary analysis of IDeate-Lung01 (JADPRO 2025) - P2, P3 | "BACKGROUND • Approximately 10-20% of patients with SCLC have BM at diagnosis, increasing to 80% after 2 years** -For patients with BM at baseline, median OS from time of diagnosis is ~5 months, with a 3-year survival rate of 3.0% In the primary analysis of IDeate-Lung01 (Phase 2; NCT05280470), I-DXd 12 mg/kg Q3W demonstrated a systemic CORR of 48.2%, mDOR of 5.3 months, and mPFS of 4.9 months in 137 patients with previously treated ES-SCLC METHODS • We report a subgroup analysis of patients with asymptomatic (previously treated or untreated) BM identified by CNS BICR at study baseline delectable by CT/MRI brain scan at baseline (Figure 1) • Brain CT/MRI was performed at baseline for all patients, and for those with investigator-determined BM, Q6W for 36 weeks and Q12W thereafter Intracranial response was assessed by CNS BICR using a version of RECIST 1.1 modified for assessment of CNS tumors RESULTS • Baseline characteristics of patients with baseline BM: -..."

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

Patient-reported outcomes (PROs) from DeLLphi-304: The first phase III trial evaluating tarlatamab and chemotherapy (CTx) in patients (Pts) with previously treated small cell lung cancer (SCLC) (ESMO 2025) - P3 | "Methods Pts were randomized to receive tarlatamab or CTx (topotecan, lurbinectedin or amrubicin) until disease progression. Conclusions Tarlatamab treatment delayed deterioration in cancer-related symptoms with a favorable benefit-risk profile and clinically meaningful improvements in quality of life. These findings reinforce tarlatamab as the new standard of care."

Clinical • P3 data • Patient reported outcomes • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

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 (JADPRO 2025) - "BACKGROUND • Despite improved efficacy with 1L immune checkpoint inhibitors (ICIs) + platinum-based chemotherapy, most patients with ES-SCLC eventually experience disease progression and long-term survival remains limited¹-⁵ • Due to the high attrition rate in ES-SCLC of ~60%⁶, offering the most effective treatment in the front-line setting before progression is crucial to improve outcomes in this difficult-to-treat disease • Lurbinectedin is an alkylating agent and transcription inhibitor that is approved in the US and other countries for the treatment of patients with metastatic SCLC who experienced disease progression on or after platinum-based chemotherapy • In pre-clinical studies, lurbinectedin was shown to synergize with ICIs⁷⁻⁸ to achieve high rates of tumor regression and induce long-term T-cell memory⁹⁻¹⁰ • In Phase 1/2 trials in patients with relapsed ES-SCLC, the combination of lurbinectedin and ICIs was well tolerated with promising..."

Clinical • P3 data • Lung Cancer • Oncology • 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 • P1 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

PharmaMar Group…received a milestone payment of $50 million from Jazz Pharmaceuticals…related to the full approval granted on October 2nd of this year from the U.S Food and Drug Administration (FDA) for Zepzelca (lurbinectedin) in combination with atezolizumab (Tecentriq) as a first-line maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) (Pharmamar Press Release)

Commercial • Small Cell Lung Cancer

IDeate-Lung02: a Phase 3 study of second-line ifinatamab deruxtecan in patients with relapsed small cell lung cancer. (PubMed, Future Oncol) - P3 | "Patients with small cell lung cancer (SCLC) have poor prognosis and limited treatment options beyond first-line therapy. Secondary endpoints include ORR by investigator; progression-free survival, duration of response, disease control rate, and time to response, all by BICR and investigator; patient-reported outcomes; and safety. IDeate-Lung02 will ascertain whether I-DXd treatment after only one prior line of systemic treatment improves outcomes for patients with relapsed SCLC compared with topotecan, amrubicin, or lurbinectedin.Clinical Trial Registration: NCT06203210."

Journal • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276

Second-line treatment strategies and clinical outcomes after progression on chemoimmunotherapy in extensive-stage small-cell lung cancer. (PubMed, Lung Cancer) - "2L survival outcomes post-CIO were similar to historical results after chemotherapy alone. Despite 1L immunotherapy, 2L response rates and survival remain poor, underscoring the need for more effective strategies in ES-SCLC."

Clinical data • Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

Modeling spinal dissemination in glioblastoma using post-mortem and ex vivo approaches (EANO 2025) - "Using these cells, we successfully established a disseminating glioblastoma model in a mouse and, importantly, detected metastasis, highlighting a persistent aggressive phenotype.Carfizomib, Lurbinectedin, Panobinostat, Ixazomib, Idasanutlin, Cobimetinib and Trametinib all showed good cytotoxic activity ex- vivo. Our study highlights that the molecular pathology of spinal LM cells closely mirrors the primary tumor, and the dissemination might occur with some degree of genetic evolution. Novel treatment approaches for this aggressive tumor cell phenotype could include a personalized treatment based on the drug-screening platform results."

Preclinical • Brain Cancer • Glioblastoma • Hematological Malignancies • Oncology • Solid Tumor • MGMT • PTCH1 • TP53

Cost-effectiveness analysis of lurbinectedin plus atezolizumab as first-line treatment for extensive-stage small-cell lung cancer. (PubMed, Front Immunol) - "At a willingness-to-pay threshold of $40,365 and $150,000 per QALY, the probability of LU-AT being cost-effective relative to AT was 0% in China and USA. Within the framework of China's and the United States' healthcare system, LU-AT is unlikely to represent a cost-effective first-line treatment for ES-SCLC."

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

Jazz Pharmaceuticals...announced that the U.S. Food and Drug Administration (FDA) has granted approval for Zepzelca (lurbinectedin) in combination with atezolizumab (Tecentriq) or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) as a maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy... (PRNewswire) - "The FDA approval is based on results from the Phase 3 IMforte trial (NCT05091567), which showed that the Zepzelca 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."

FDA approval • Small Cell Lung Cancer