Calsed (amrubicin) / Sumitomo Pharma, BMS, Nippon Kayaku - LARVOL DELTA

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 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

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

Efficacy and Safety of ABBV-706 Versus Standard of Care in Relapsed/Refractory Small Cell Lung Cancer: A Phase 3 Study (IASLC-WCLC 2026) - P1, P3 | "Tarlatamab, a recommended standard of care (SOC) in second line (2L) for patients with ES-SCLC with disease progression on or after platinum-based chemotherapy, offers improved response rates in heavily treated relapsed/refractory (R/R) patients; however, treatment options in this setting are still limited...Methods : M23-384 (NCT07365241) is a Phase 3, global, randomized, open-label, multicenter (~175 sites) study, evaluating the safety and efficacy of ABBV-706 versus SOC (topotecan, lurbinectedin, or amrubicin) in patients with R/R SCLC...Key secondary endpoints include progression-free survival and duration of response based on BICR assessment per RECIST v1.1, patient-reported outcomes (change from baseline at Week 12 in physical functioning as measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30], and in Global Health Status [GHS]/QoL as measured by the EORTC QLQ-C30 GHS/QoL scale), and..."

Clinical • First-in-human • P3 data • CNS Disorders • Epilepsy • Interstitial Lung Disease • Lung Cancer • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • SEZ6

Intracranial efficacy of tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): DeLLphi-304 phase 3 post hoc analysis. (ASCO 2026) - P3 | " Pts were randomized 1:1 to receive tarlatamab or CTx (topotecan, lurbinectedin or amrubicin) as 2L treatment for SCLC. Tarlatamab demonstrated increased intracranial efficacy with longer CNS PFS and OS vs CTx in pts with stable, treated and untreated asymptomatic BM. These results affirm tarlatamab as the 2L standard of care for SCLC, even in pts with BM. aAssessed in pts with ≥1 lesion that was ≥ 10 mm."

Clinical • P3 data • Retrospective data • Brain Cancer • CNS Tumor • 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

Association of CBR3 Rs8133052 With PFS in Relapsed SCLC Treated With Second-Line or Later Amrubicin (IASLC-WCLC 2026) - "Introduction : Although treatment options for relapsed small cell lung cancer (SCLC) beyond first-line therapy are evolving with the introduction of tarlatamab, cytotoxic chemotherapy remains clinically important...For doxorubicin, another anthracycline agent, genetic polymorphisms affecting drug transporters and metabolizing enzymes have been reported to influence pharmacokinetics, including the area under the curve (AUC), pharmacodynamics, and clinical outcomes...Conclusions : The CBR3 rs8133052 GG genotype was independently associated with shorter PFS in patients with relapsed SCLC receiving second-line or later amrubicin therapy. The association with PFS, but not with severe adverse events, suggests that CBR3 genetic variation may modulate antitumor efficacy, possibly through differential AMR metabolism at the tumor site, although this mechanism warrants further investigation."

Clinical • IO biomarker • Lung Cancer • Small Cell Lung Cancer • Solid Tumor • ABCB1 • CBR3 • NQO1

Clinical Outcomes of Second-Line Amrubicin and Platinum-Based Doublet Chemotherapy in Patients with Extrapulmonary Neuroendocrine Carcinoma: A Multicenter Retrospective Study. (PubMed, Cancers (Basel)) - "Grade 3-4 hematologic toxicity was more frequent in the platinum group, whereas severe non-hematologic toxicity was rare in both groups. AMR therapy and platinum-based doublet therapy may exhibit comparable efficacy and acceptable safety profiles as second-line treatment options for advanced EPNEC."

Clinical data • Journal • Retrospective data • Endocrine Cancer • Neuroendocrine Carcinoma • 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

A Phase 3 Study of Sacituzumab Govitecan in Patients With Previously Treated Extensive Stage Small Cell Lung Cancer (IASLC-WCLC 2025) - P3 | "EVOKE-SCLC-04 (NCT06801834) is a global, multicenter, randomized, open-label, phase 3 study evaluating the efficacy and safety of SG versus SOC (topotecan or amrubicin [Japan only]) in previously treated patients with ES-SCLC. Secondary endpoints include progression-free survival, duration of response, patient-reported outcomes (time to first deterioration in shortness of breath and physical functioning), and safety/tolerability. This study is open and actively recruiting as of February 2025 and is planning to enroll 695 patients from approximately 200 sites globally."

Clinical • P3 data • CNS Disorders • Infectious Disease • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor

A phase 3 study of sacituzumab govitecan in patients with previously treated extensive-stage small cell lung cancer. (ASCO 2026) - P3 | "Prior tarlatamab treatment is allowed...Patients will be randomized 1:1 to either SG (10 mg/kg on Days 1 and 8) or SOC: topotecan (1.5 mg/m2 daily on Days 1–5), lurbinectedin (3.2 mg/m2 on Day 1), or amrubicin (40 mg/m2 daily on Days 1–3) administered as intravenous infusion in 21-day cycles, until progressive disease (assessed by investigator review per RECIST v1.1), unacceptable toxicity, or death...The primary endpoint is OS; secondary endpoints include progression-free survival, ORR, duration of response, patient-reported outcomes (time to first deterioration in shortness of breath and physical functioning), and safety/tolerability. This study is open and actively recruiting as of February 2025 and plans to enroll 695 patients from approximately 275 sites globally."

Clinical • P3 data • CNS Disorders • Infectious Disease • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor

Pulmonary carcinoid harboring a KRAS G12C mutation identified through comprehensive genomic profiling and responding to sotorasib: A case report. (PubMed, Rare Tumors) - "The patient was treated sequentially with carboplatin plus etoposide, everolimus, and amrubicin, however, the liver metastases progressed. Sotorasib is effective for treating KRAS G12C-positive pulmonary carcinoids. Because pulmonary NETs rarely harbor driver mutations, CGP testing may be considered."

Journal • Gastrointestinal Neuroendocrine Tumor • Liver Cancer • Lung Adenocarcinoma • Lung Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

A Study to Evaluate Adverse Events and Change in Disease Activity of Intravenous ABBV-706 Versus Standard of Care in Adult Participants With Relapsed/Refractory Small Cell Lung Cancer (clinicaltrials.gov) - P3 | N=531 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • 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 | Recruiting | Sponsor: Daiichi Sankyo | Trial completion date: Feb 2029 ➔ Dec 2029 | Trial primary completion date: Apr 2027 ➔ Jan 2028

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

EGFR Wild-Type Sarcomatoid Carcinoma as Acquired Resistance to Tarlatamab in Small Cell-Transformed EGFR-Mutated Lung Adenocarcinoma: A Case Report. (PubMed, JTO Clin Res Rep) - "After surgery, she received osimertinib and adjuvant cisplatin plus etoposide...Carboplatin plus etoposide and amrubicin were ineffective, whereas third-line tarlatamab induced the disappearance of liver metastases and disease control for 10 months...Genomic analyses revealed a shared TP53 p.H168P mutation across sequential specimens, whereas the recurrent SCLC and tarlatamab-resistant sarcomatoid carcinoma lacked the original EGFR p.E746_A750del-mutant allele. This case highlights dynamic histologic and molecular evolution in EGFR-mutated lung cancer and suggests that tarlatamab resistance may involve the selection of DLL3-negative clones."

Journal • Preclinical • Hepatology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • DLL3 • EGFR • TP53

Development of a simplified population pharmacokinetic-pharmacodynamic framework for exposure-informed risk stratification of neutropenia during amrubicin treatment. (PubMed, Cancer Chemother Pharmacol) - "We developed a simplified PK-PD framework and implemented it in a prototype application to support risk stratification of neutropenia during amrubicin treatment. The framework does not provide dose recommendations but may support identification of patients who could benefit from prophylactic supportive care, such as pegylated G-CSF. Prospective studies are ongoing to evaluate its clinical utility."

Journal • PK/PD data • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

Matching-Adjusted Indirect Comparison of Tarlatamab for Patients with Platinum-Refractory or Platinum-Resistant Extensive-Stage Small-Cell Lung Cancer. (PubMed, Adv Ther) - P2, P3 | "These results suggest that tarlatamab may increase survival relative to paclitaxel and CAV among individuals with platinum-refractory or platinum-resistant ES-SCLC in the 2L setting. These findings are subject to residual confounding and should be interpreted with caution."

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

Platinum rechallenge versus non-platinum regimens as second-line treatment for advanced thymoma: Analysis of the largest retrospective cohort to date. (ASCO 2026) - P=N/A | " Among the 91 patients (median age 59; 91% ECOG PS 0-1) with a median follow-up of 1056 days, 64 (70%) received Pt-rechallenge and 27 received non-Pt regimens (S-1 [tegafur/gimeracil/oteracil], n=15; pemetrexed, n=6; amrubicin, n=5; paclitaxel, n=1). In this largest comparative study to date, platinum rechallenge demonstrated superior response rates compared to non-platinum regimens, particularly in patients with favorable PFI. Study registration: UMIN000048181."

Metastases • Retrospective data • Solid Tumor • Thymoma • Thymus Cancer

Comparative efficacy of tarlatamab and second-line therapies in extensive-stage small cell lung cancer: A network meta-analysis. (PubMed, Lung Cancer) - "Tarlatamab demonstrated statistically significant and clinically meaningful improvement in OS compared with all currently available 2L treatments for ES-SCLC in the overall 2L population and platinum-sensitive subgroup, supporting its potential as a new SOC."

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

A multi-institutional, single-arm, phase 2 study of durvalumab plus amrubicin in patients with relapsed extensive-stage small cell lung cancer (Aphrodite trial). (ASCO 2026) - P | "The combination therapy of durvalumab and AMR suggests favorable efficacy and tolerable safety, particularly in pts with RR, even in those who had already received ICI treatment."

Clinical • P2 data • Febrile Neutropenia • Infectious Disease • Lung Cancer • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor

Real-World Data of Second-Line Amrubicin Monotherapy in Patients With Extensive-Stage Small Cell Lung Cancer Who Received First-Line Chemoimmunotherapy or Chemotherapy: A Multicenter Retrospective Study. (PubMed, Cancer Med) - "Second-line amrubicin monotherapy for relapsed SCLC may be useful and well-tolerated as a treatment option after first-line chemoimmunotherapy or chemotherapy."

Journal • Monotherapy • Real-world evidence • Retrospective data • Febrile Neutropenia • Hematological Disorders • Interstitial Lung Disease • Lung Cancer • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor

Life-Threatening Prolonged ICANS Following Tarlatamab Treatment in Extensive-Stage Small Cell Lung Cancer With Brain Metastases: A Case Report. (PubMed, Respirol Case Rep) - "She had previously received first-line carboplatin, etoposide, and durvalumab, followed by second-line amrubicin. The absence of allergic predisposition or prior neurologic symptoms suggested that untreated intracranial disease, rather than host factors, contributed to the unusually severe and prolonged ICANS. This case highlights that occult or untreated brain metastases may increase susceptibility to life-threatening ICANS during tarlatamab therapy."

Journal • CNS Disorders • Epilepsy • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Tarlatamab vs. Platinum-Based Retreatment in Relapsed Small Cell Lung Cancer: A Comparative Analysis (HOPA 2026) - "In the recent Delphi-304 trial, tarlatamab was compared to topotecan, lurbinectedin, or amrubicin as second-line therapy, and tarlatamab resulted in longer overall survival (OS) than chemotherapy. A total of 85 patients were included in the final analysis with 39 patients receiving retreatment with platinum doublet and 46 patients receiving tarlatamab. The median age at treatment initiation was 69 years. Of these patients, 42 (49.4%) were male and 43 (50.5%) female and 76 (89.4%) patients included were Caucasian."

Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A Retrospective Multicenter Study to Examine the Risk Factors for Febrile Neutropenia during Amrubicin Hydrochloride Therapy for Recurrent Small Cell Lung Cancer (PubMed, Yakugaku Zasshi) - "Multivariate analysis demonstrated that performance status (PS) >2 (odds ratio: 5.8, 95% confidence interval: 1.70-19.80, p=0.005) and hematocrit (HCT) (odds ratio: 0.93, 95% confidence interval: 0.877-0.994, p=0.033) were significantly associated with FN development. These findings suggest that PS and HCT may serve as key indicators for predicting FN during AMR therapy in patients with recurrent SCLC."

Clinical • Journal • Retrospective data • Febrile Neutropenia • Hematological Disorders • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor

Initial Experience with Tarlatamab in Patients with SCLC and at least two previous lines of therapy (DKK 2026) - "Recently the randomized Phase III trial DeLLphi-304 has shown superiority as compared to chemotherapy as second line therapy (topotecan; lurbinectedin or amrubicin) with respect to OS, RR, PFS and DoR accompanied with fewer high grade side effects. Tarlatamab demonstrated a promising clinical activity and a manageable safety profile in patients with relapsed or refractory SCLC. These findings support the further development of tarlatamab as a potential targeted therapy in this difficult-to-treat population."

Clinical • Infectious Disease • Inflammation • Lung Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3