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BMC Cancer
Published in: BMC Cancer 1/2023

Open Access 01-12-2023 | NSCLC | Research

A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer

Authors: Ernest Nadal, Mansoor Saleh, Santiago Ponce Aix, Maria Ochoa-de-Olza, Sandip Pravin Patel, Scott Antonia, Yumin Zhao, Ivelina Gueorguieva, Michael Man, Shawn T. Estrem, Jiangang Liu, Emin Avsar, Wen Hong Lin, Karim A. Benhadji, Leena Gandhi, Susan C. Guba, Inmaculada Ales Diaz

Published in: BMC Cancer | Issue 1/2023

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Abstract

Background

In this phase Ib/II open-label study, tumor immune suppression was targeted in patients with advanced refractory solid tumors and patients with recurrent/refractory non-small cell lung cancer (NSCLC) using galunisertib with nivolumab.

Methods

Eligible patients were ≥ 18 years old, had an Eastern Cooperative Oncology Group performance status ≤ 1, and were treatment-naive for anti-programmed cell death-1, its ligand, or transforming growth factor β receptor 1 kinase inhibitors. Phase Ib was an open-label, dose-escalation assessment of the safety and tolerability of galunisertib with nivolumab in patients with advanced refractory solid tumors. Phase II evaluated the safety of galunisertib with nivolumab in NSCLC patients who had received prior platinum-based treatment but were immuno-oncology agent-naive.

Results

This trial was conducted between October 2015 and August 2020. No dose-limiting toxicities were observed in phase I. In the phase II NSCLC cohort (n = 25), patients received 150 mg twice daily galunisertib (14 days on/14 days off dosing schedule for all phases) plus nivolumab at 3 mg/kg (intravenously every 2 weeks). In this phase, the most frequent treatment-related adverse events (AEs) were pruritus (n = 9, 36%), fatigue (n = 8, 32%), and decreased appetite (n = 7, 28%). No grade 4 or 5 treatment-related AEs were observed. Six (24%) patients had confirmed partial response (PR) and 4 (16%) had stable disease; 1 additional patient had confirmed PR after initial pseudo-progression. The median duration of response was 7.43 months (95% confidence interval [CI]: 3.75, NR). Among the 7 responders, including the delayed responder, 1 had high PD-L1 expression (≥ 50%). The median progression-free survival was 5.26 months (95% CI: 1.77, 9.20) and the median overall survival was 11.99 months (95% CI: 8.15, NR). Interferon gamma response genes were induced post-treatment and cell adhesion genes were repressed, although the association of these observations with tumor response and clinical outcomes was not statistically powered due to limited samples available.

Conclusions

The study met its primary endpoint as galunisertib combined with nivolumab was well tolerated. Preliminary efficacy was observed in a subset of patients in the Phase 2 NSCLC cohort.

Trial registration

Trial registered with ClinicalTrials.gov (NCT02423343; 22.04.2015).
Appendix
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Metadata
Title
A phase Ib/II study of galunisertib in combination with nivolumab in solid tumors and non-small cell lung cancer
Authors
Ernest Nadal
Mansoor Saleh
Santiago Ponce Aix
Maria Ochoa-de-Olza
Sandip Pravin Patel
Scott Antonia
Yumin Zhao
Ivelina Gueorguieva
Michael Man
Shawn T. Estrem
Jiangang Liu
Emin Avsar
Wen Hong Lin
Karim A. Benhadji
Leena Gandhi
Susan C. Guba
Inmaculada Ales Diaz
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-023-11153-1

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