Results from the multicenter phase I/II SCOOP trial exploring the combination of the stemness inhibitor napabucasin (BBI608) and the PD-1 inhibitor pembrolizumab (Keytruda) demonstrated an acceptable safety profile in patients with metastatic colorectal cancer (mCRC).
during the GI Symposium, lead investigator Akihito Kawazoe, MD, of the Department of Gastroenterology and Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan, discussed the study of napabucasin plus pembrolizumab in mCRC.
OncLive: Can you please provide some background on napabucasin?
We know that pembrolizumab showed an objective response rate (ORR) of 40% in microsatellite instability-high (MSI-H) CRC. On the other hand, it showed an ORR of 0% in patients with MSS CRC. It has been reported that WNT/β-catenin signaling has been involved in the elimination of lymphocyte infiltration and resistance to anti–PD-1. CRC is a tumor in which we need better catenin signaling activation. Preclinical models show that napabucasin in combination with anti–PD-1 shows antitumor activity. Thus, we initiated a phase I/II study of napabucasin in combination with pembrolizumab for CRC.
The study has 2 cohorts. Cohort A is MSI-H CRC, and the target number is 10. Cohort B is MSS CRC, with a target number of 40.
What did you find?
The safety profile is tolerable and expected with no DLTs. We decided to recommend a phase II dose of napabucasin at 480 mg per day with pembrolizumab at a fixed dose. One patient on 480 mg per day of napabucasin showed remarkable shrinkage. Also, a biomarker analysis showed that [there was] CD8 infiltration inside the tumor; this was observed by immunohistochemistry and flow cytometry.
What impact could this study have on clinical practice for mCRC?
There are unmet medical needs for MSS CRC in the development of immunotherapy. We will have those promising results in this study, so that we can [hopefully] change the [state of] immunotherapy in MSS CRC by this combination of napabucasin and pembrolizumab.
What do you predict to be the next steps of this combination?
We can show the promising result in this phase I/II trial, so then [we can begin] the phase III trial for MSS CRC of this combination in the future.
Kawazoe A, Kuboki Y, Komatsu Y, et al. Multicenter phase I/II trial of BBI608 and pembrolizumab combination in patients with metastatic colorectal cancer (SCOOP Study): EPOC1503. J Clin Oncol. 2018;36(suppl 4S; abstr 760).
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