eribulin liposomal (E7389-LF) / Eisai, Ono Pharma - LARVOL DELTA

A Study of E7389 Liposomal Formulation (E7389-LF) Plus Nivolumab in Participants With Solid Tumor (clinicaltrials.gov) - P1/2 | N=125 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Phase classification: P1b/2 ➔ P1/2 | Trial completion date: Jan 2024 ➔ Mar 2026 | Trial primary completion date: Jan 2024 ➔ Mar 2026

Phase classification • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Liposomal eribulin (E7389-LF) plus nivolumab: a potential treatment option for patients with advanced gastric cancer? (PubMed, J Gastrointest Oncol) - No abstract available

Journal • Metastases • Gastric Cancer • Oncology • Solid Tumor

Phase 1b/2 study of the liposomal formulation of eribulin (E7389-LF) in combination with nivolumab: Results from the phase 2 esophageal cancer cohort. (PubMed, BJC Rep) - P1b/2 | "E7389-LF plus nivolumab showed antitumor activity in patients with unresectable and pretreated esophageal cancer and should be evaluated further in a broader population."

Combination therapy • IO biomarker • Journal • P1/2 data • P2 data • Esophageal Cancer • Hematological Disorders • Leukopenia • Neutropenia • Oncology

E7389-J081-114: Study of E7389 Liposomal Formulation in Participants With Solid Tumor (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Aug 2025 ➔ Mar 2026

Trial completion date • Breast Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

Phase 1b/2 study of the liposomal formulation of eribulin (E7389-LF) in combination with nivolumab: Results from the phase 2 esophageal cancer cohort (Nature) - P1/2 | N=125 | NCT04078295 | Sponsor: Eisai Co., Ltd. | "Of the 35 Japanese patients enrolled, 7 (20.0%) had a partial response as their best overall response, and 14 (40.0%) had stable disease. The ORR was 20.0% (95% CI 8.4–36.9). The duration of response was 5.6 months (95% CI 1.7–not estimable [NE]). The median PFS was 2.81 months (95% CI 1.31–4.17). The median OS was not reached (95% CI 6.54 months–NE). The most common treatment-emergent adverse events were neutropenia (65.7%), pyrexia (60.0%), and leukopenia (57.1%). Select plasma endothelial cell markers levels increased from day 1 of cycle 1 and changes were pronounced between days 8–15 of each cycle."

P2 data • Esophageal Cancer

Combination activity of eribulin liposomal formulation and anti-PD-1 antibody after tumor regrowth during anti-PD-1 antibody treatment in mice (AACR 2024) - P1b/2 | "Currently, Phase 1b/2 clinical trial of ERI-LF plus nivolumab in patients with selected solid cancers (NCT04078295) is underway. Patients with or without prior ICI therapy were enrolled in a small cell lung cancer cohort of this clinical study. Our preclinical results might provide a scientific rationale for a uniqueness of ERI-LF as a post ICI therapy."

IO biomarker • Preclinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD4 • CD8

E7389-J081-114: Study of E7389 Liposomal Formulation in Participants With Solid Tumor (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Aug 2024 ➔ Aug 2025

Trial completion date • Breast Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

Phase 2 Small Cell Lung Cancer (SCLC) Cohort of liposomal Eribulin with nivolumab: Overall survival (OS) Update (JSMO 2024) - No abstract available

Clinical • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Results of a 2 Trial of E7389-LF+nivolumab (NIVO) in Patients (PTS) with Gastric (GC) or Esophageal Cancers (EGC) (JSMO 2024) - No abstract available

Clinical • Esophageal Cancer • Gastrointestinal Cancer • Oncology

E7389-LF AS 1L 1L Chemotherapy for Advanced/Metastatic HER2-Negative Breast Cancer (HER2-BC): Phase 1 Dose-Expansion Study (JSMO 2024) - No abstract available

Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • HER-2

Phase 2 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Gastric Cancer Cohort (Clin Cancer Res) - P1b/2 | N=125 | NCT04078295 | Sponsor: Eisai Co., Ltd. | "In the 31 patients who received E7389-LF in combination with nivolumab, ORR was 25.8% (95% CI 11.9–44.6). The median PFS was 2.69 months (95% CI 1.91–2.99) and median OS was 7.85 months (95% CI 4.47–not estimable). The most common treatment-related TEAEs of any grade were neutropenia (77.4%), leukopenia (74.2%), and decreased appetite (51.6%). E7389-LF in combination with nivolumab significantly increased CD8-positive cells at C2D1 (P=0.039), and 6 of 7 vascular markers and 4 interferon-gamma–related markers showed increases from C1D1."

P2 data • Gastric Cancer

Phase 2 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Gastric Cancer Cohort. (PubMed, Clin Cancer Res) - "Promising antitumor activity was observed with E7389-LF in combination with nivolumab in patients with GC, and no new safety signals were observed, compared with either monotherapy."

Combination therapy • Journal • P2 data • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Solid Tumor • CD8 • IFNG

Phase 2 Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Small Cell Lung Cancer Cohort. (PubMed, Cancer Res Commun) - "E7389-LF 2.1mg/m2 in combination with nivolumab 360mg Q3W showed notable antitumor activity as second-line therapy for SCLC; no new safety signals were observed compared to either agent as monotherapy."

Combination therapy • Journal • P2 data • Hematological Disorders • Lung Cancer • Neutropenia • Oncology • Small Cell Lung Cancer • Solid Tumor

E7389-LF as a first-line (1L) chemotherapy for patients (pts) with metastatic/advanced HER2-negative breast cancer (HER2− BC): Results from a phase I study dose-expansion part (ESMO 2023) - P1 | "Changes in vasculature- and IFNγ-related serum markers were noted. Conclusions E7389-LF showed promising efficacy and a manageable toxicity profile and should be explored as a 1L treatment option for pts with advanced HER2− BC."

Clinical • IO biomarker • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • IFNG • PD-L1

EISAI TO PRESENT RESEARCH FROM ONCOLOGY PORTFOLIO AND PIPELINE AT ESMO CONGRESS 2023 (Eisai Press Release) - "Eisai...announced today the presentation of research across various types of cancer from its oncology portfolio and pipeline during the European Society for Medical Oncology (ESMO) Congress 2023....Research from Eisai’s pipeline will be featured in a poster presentation of findings from the dose-expansion portion of a Phase 1 study evaluating E7389-LF, a liposomal formulation of eribulin, as a potential first-line chemotherapy treatment option for patients with metastatic/advanced HER2-negative breast cancer (Presentation: #405P). Additionally, insights from preclinical research on farletuzumab ecteribulin (FZEC, formerly known as MORAb-202), a folate receptor alpha (FRα)-targeting antibody drug conjugate (ADC), in endometrial cancer will be presented (Presentation: #786P)."

P1 data • Preclinical • Endometrial Cancer • HER2 Negative Breast Cancer

E7389-J081-114: Study of E7389 Liposomal Formulation in Participants With Solid Tumor (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Mar 2024 ➔ Aug 2024 | Trial primary completion date: Mar 2024 ➔ Aug 2024

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

Phase Ib/II Study of a Liposomal Formulation of Eribulin (E7389-LF) plus Nivolumab in Patients with Advanced Solid Tumors: Results from Phase Ib. (PubMed, Cancer Res Commun) - "The combination was tolerable overall; 4 patients had a partial response. Vasculature and immune-related biomarker levels increased, suggesting vascular remodeling."

Journal • Metastases • P1 data • P1/2 data • Oncology • Solid Tumor

E7389-J081-114: Study of E7389 Liposomal Formulation in Participants With Solid Tumor (clinicaltrials.gov) - P1 | N=140 | Active, not recruiting | Sponsor: Eisai Co., Ltd. | Trial completion date: Aug 2023 ➔ Mar 2024 | Trial primary completion date: Apr 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PD-L1

Pilot study of a micro-organosphere drug screen platform to lead care in advanced breast cancer (MODEL-ABC). (ASCO 2023) - P=N/A | "The patient subsequently received single agent chemotherapy per physicians’ choice with either carboplatin, capecitabine, paclitaxel, eribulin, liposomal doxorubicin, gemcitabine, or vinorelbine. Our platform enables efficient establishment of MOS from ABC patient samples and allows for drug dosing studies to be performed in a clinically meaningful timeframe. Our preliminary data suggests it is feasible to obtain biopsies for MOS development and perform drug screens within 14 days. These findings provided the foundation for evaluating this technology as a potential ABC diagnostic tool and warrants further clinical development in ABC."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Phase 2 small cell lung cancer (SCLC) cohort of a phase 1b/2 trial of a liposomal formulation of eribulin in combination with nivolumab. (ASCO 2023) - P1b/2 | "E7389-LF in combination with nivolumab showed notable antitumor activity as 2L therapy in pts with SCLC, as evidenced by the notable ORR of 24.2%. No new safety signals were observed for this combination. Clinical trial information: NCT04078295."

Combination therapy • IO biomarker • P1/2 data • P2 data • Acute Kidney Injury • Cardiovascular • Cough • Hematological Disorders • Immune Modulation • Lung Cancer • Nephrology • Neuroendocrine Tumor • Neutropenia • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor

Eisai Delivers New Data and Highlights Continued Progress of Oncology Portfolio and Pipeline at ASCO 2023 (PRNewswire) - "Additional data from Eisai's pipeline include a poster presentation of findings from a Phase 1b study of E7386, a CREB-binding protein (CBP) / β-catenin interaction inhibitor, in combination with lenvatinib in patients with advanced HCC...and the small cell lung cancer cohort of a Phase 1b/2 trial evaluating E7389-LF, a new liposomal formulation of eribulin, in combination with nivolumab...Insights from preclinical testing of farletuzumab ecteribulin (FZEC), formerly known as MORAb-202, and MORAb-109, antibody drug conjugates (ADC), in rare gynecologic cancers will also be published online."

P1 data • P1/2 data • Preclinical • Gastrointestinal Cancer • Gynecologic Cancers • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Metastatic urothelial carcinoma: Eribulin, with or without gemcitabine, to treat the second most deadly GU cancer (SWOG-Spring 2023) - No abstract available.

Phase 1 Dose Escalation Study of the Liposomal Formulation of Eribulin (E7389-LF) in Japanese Patients with Advanced Solid Tumors. (PubMed, Clin Cancer Res) - "E7389-LF was well-tolerated at 2.0 mg/m Q3W and 1.5 mg/m Q2W. Considering the toxicity profile of both regimens, the recommended dose was 2.0 mg/m Q3W. Expansion cohorts are ongoing."

Journal • P1 data • Febrile Neutropenia • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Solid Tumor • CD31 • FLT4 • ICAM1 • IFNG

Gastric cancer (GC) cohort of a phase 2 trial of E7389-LF (liposomal formulation of eribulin) in combination with nivolumab. (ASCO-GI 2023) - P1b/2 | "E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg Q3W had promising efficacy for pretreated GC, as evidenced by the notable ORR of 25.8% as well as by PFS and OS. No new safety signals were identified for this combination. Biomarker changes suggested vascular remodeling activity and enhancement of antitumor immunity via IFNγ signaling."

Combination therapy • IO biomarker • P2 data • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IFNG • PD-L1

The esophageal cancer cohort of a phase 2 trial of E7389-LF (liposomal formulation of eribulin) + nivolumab. (ASCO-GI 2023) - P1b/2 | "E7389-LF combined with nivolumab showed an ORR of 22.9% in pts with EGC. Despite this modest ORR, the DCR of 62.9% was notable. No new safety signals were observed compared to the known profiles of each monotherapy."

P2 data • Esophageal Cancer • Gastrointestinal Cancer • Oncology