Phase 1/2, open-label study of oral bacterial supplementation (EDP1503) plus pembrolizumab in participants with advanced or metastatic microsatellite-stable colorectal cancer, triple-negative breast cancer, and checkpoint inhibitor–relapsed tumors
Judy S. Wang, Edward Arrowsmith, J. Thaddeus Beck, Jennifer Friedmann, Rahima Jamal, Duncan McHale, Humphrey Gardner, Michael Chisamore, Susanna V. Ulahannan
Abstract
We report a phase 1/2 study evaluating EDP1503 (capsule containing Bifidobacterium animalis lactis) ± pembrolizumab in participants with microsatellite-stable colorectal cancer (MSS CRC), triple-negative breast cancer (TNBC), or other tumor types that relapsed after responding to immunotherapy (KEYNOTE-939/EDP1503-101; NCT03775850). Participants (≥ 18 years) had confirmed advanced/metastatic tumors and progressive disease (PD), were intolerant/nonresponsive to recommended treatment, and had measurable disease (RECIST v1.1). Cohorts were: MSS CRC (Cohort A), metastatic/locally advanced TNBC (Cohort B), and PD following partial response/stable disease for ≥ 6 months during anti‒PD-(L)1 therapy (≥ 8 months during anti‒PD-(L)1 therapy plus chemotherapy for non-small-cell lung cancer) (Cohort C). Participants received oral EDP1503 (2 or 4 capsules twice daily [BID]) for 2 weeks, then EDP1503 (2 or 4 capsules BID) plus intravenous pembrolizumab 200 mg every 3 weeks until PD, participant withdrawal, investigator decision, intolerable toxicity, or completion of 35 cycles. Primary endpoints were safety/tolerability, objective response rate (RECIST v1.1), and immune-response rate. Secondary endpoints included duration of clinical benefit, progression-free survival (PFS), and overall survival (OS). Of 69 participants, objective responses were observed in 3 (2 in Cohort B and 1 in Cohort C with partial responses received 4 capsules BID). For participants receiving 4 capsules BID, median duration of clinical benefit (95% CI) was 8.7 months (5.5 months‒not evaluable), median PFS was 1.8 (1.7‒1.9) months, and median OS was 7.8 (2.5‒13.5) months. Grade ≥ 3 adverse events occurred in 28 participants (40.6%), with no new safety signals. EDP1503 plus pembrolizumab had manageable safety but limited clinical activity.Trial registration: KEYNOTE-939, EDP1503-101 trial: ClinicalTrials.gov NCT03775850.