Phase II Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Small Cell Lung Cancer Cohort

Abstract

Purpose: E7389-LF is a liposomal formulation of eribulin that contributes to tumor vascular remodeling. The phase 2 part of this phase 1b/2 study assessed the efficacy/safety of E7389-LF in combination with nivolumab in several disease cohorts; herein, we report results from the small cell lung cancer (SCLC) cohort. Patients and Methods: Patients with unresectable/measurable SCLC and disease progression with first-line platinum-based chemotherapy with/without an immune-checkpoint inhibitor (ICI) were enrolled to receive E7389-LF 2.1mg/m2 plus nivolumab 360mg intravenously Q3W. The primary objective of this part was to assess the objective response rate (ORR). Secondary objectives included assessments of safety and progression-free survival (PFS); exploratory assessments included overall survival (OS) and biomarkers. Results: Thirty-four patients were enrolled. By the data cutoff date (May 31, 2022), 29 (85.3%) had discontinued. Efficacy/biomarker analyses included 33 patients (1 had their diagnosis changed postenrollment); the ORR of E7389-LF plus nivolumab was 24.2% (95% CI 11.1–42.3), the median PFS was 3.98 months (95% CI 2.63–4.40), and, at a median follow-up of 10.6 months, the median OS was not reached (95% CI not estimable). Notably, 27/33 patients (81.8%) had received an ICI as their prior first-line therapy. Treatment-related, treatment-emergent adverse events occurred in 97.1% (any grade) and 82.4% (grade ≥3) of enrolled patients; the most common event was neutropenia. Changes in vascular and immune-related plasma markers were observed. Conclusions: 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.

The Evolving Scenario of ES-SCLC Management: From Biology to New Cancer Therapeutics

“…There were great expectations of the PARPis; however, taking together the results from the various clinical trials, we can conclude that the activity of these drugs administered alone or in combination with different drugs (CT, ICI and mTKI) is poor in an unselected patient population [ 110 , 134 , 139 , 140 , 141 , 142 , 143 , 144 ]. Some studies reported that SLFN11 is a predictor of response to platinum and PARPis in SCLC [ 12 , 130 , 221 ].…”

“…In order to improve the effectiveness of anti-PD-(L)-1, attempts have been made to combine these ICIs with other drugs. In several studies, anti-PD1 was combined with chemotherapy (amrubicin, paclitaxel, gemcitabine, and liposomal formulation [LF]-eribulin) in pretreated patients with SCLC but with limited benefit, as reported in Table S9 [ 139 , 140 , 141 , 142 ]. Two phase II trial evaluated apatinib (anti-VEGFR2) plus camrelizumab (an anti-PDL-1) and anlotinib (a multi-tyrosine kinase inhibitor [mTKI]) plus penpulimab (an anti-PDL-1) [ 143 , 144 ].…”