Study design and participants
NSCLC, colorectal cancer, tumor, CRC, PAD, Tumors
COLORECTAL CANCER, TUMOR, DISEASE, SOLID TUMORS, TUMORS, PAD, NSCLC
ECHO-206 (NCT02959437) was an international, open-label, Phase I/II study in which patients received an epigenetic priming regimen and an immunotherapy doublet consisting of epacadostat and pembrolizumab. The study was undertaken at 11 centers in the United States, United Kingdom, and Spain. Patients enrolled in Phase I had confirmed advanced or metastatic solid tumors and had failed prior standard treatment (no limit to the number of prior regimens). Phase II planned to enroll several refractory solid tumors and ultimately included NSCLC and microsatellite stable (MSS) colorectal cancer (CRC) cohorts. NSCLC patients with prior anti-PD(L)1 were selected because this tumor type is known to be responsive to anti-PD(L)1 therapy, and combination with an epigenetic modifier was hypothesized to improve or restore antitumor activity. MSS CRC does not have a high mutational burden, and the lack of immunogenicity makes this histology unlikely to respond to immunotherapy alone. MSS CRC became a tumor type of interest based on preclinical data suggesting that epigenetic reprogramming could increase the immunogenicity of the tumor and synergize with anti-PD(L1) immunotherapy to promote antitumor activity [Patients in both study phases were adults (≥18 years) with disease that was measurable per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [The Phase I study, which sought to determine the maximum tolerated dose (MTD) or pharmacologically active dose (PAD) of the triple-drug combination, employed a 3 + 3 + 3 study design. The Phase II study employed a Simon two-stage design and consisted of dose-expansion cohorts (to assess the safety and efficacy of the MTD or PAD) and treatment-sequencing, tumor-biopsy cohorts (to evaluate epigenetic changes, as well as changes in the tumor microenvironment). Patients in the dose-expansion cohorts had either NSCLC or MSS CRC and were required to undergo two biopsies, one before treatment and one prior to day 1 of cycle 3 (see Additional file 1: Supplementary Fig. 