Abstract CT149: BOLD-100-001 (TRIO039): a phase 1b/2a dose-escalation study of BOLD-100 in combination with FOLFOX chemotherapy in patients with pre-treated advanced colorectal cancer: interim efficacy, safety and tolerability analysis

Abstract Background: BOLD-100 is a first-in-class ruthenium-based anticancer agent in Phase 1b/2a clinical development for the treatment of advanced gastrointestinal (GI) cancers in combination with FOLFOX. BOLD-100 demonstrated synergy in established preclinical models in combination with various anticancer therapies, particularly in resistant cell lines. In the first interim analysis of the phase 1b dose-escalation component of the clinical trial, BOLD-100 plus FOLFOX was well-tolerated in patients (pts) with advanced GI solid cancers. Methods: This is a prospective, Phase 1b dose-escalation (Part A) and Phase 2a dose-expansion (Part B) study of BOLD-100 in combination with FOLFOX for colorectal (CRC), pancreatic (PDAC), gastric (GC) and biliary tract (BTC) cancers. Pts receive BOLD-100 with FOLFOX on day 1 of each 14-day cycle. In Part A, pts were enrolled in a 3+3 design to determine the combination recommended Phase 2 dose (RP2D), with BOLD-100 dose-escalation (420, 500 and 625 mg/m2). Part B comprises 4 cohorts treated at the RP2D of 625 mg/m2 until progressive disease or unacceptable toxicity. The primary objective of Part B is to evaluate the efficacy of BOLD-100 in three clinical endpoints (PFS, OS, and ORR). Bayesian modelling is used to continually reassess these endpoints; the posterior probability of superiority to a historical landmark for each endpoint. Results: As of 31 Dec 2022, 17 pts with advanced metastatic colorectal cancer median age 62 years were treated. Pts received a median of 4 prior systemic therapies, 14 had received prior FOLFOX and 16 (94%) were enrolled with stage IV disease. Median number of cycles completed was 7 (range 1-12). Median PFS was 4.7 [2.9,8.6] months, median OS 9.8 [5.2,22] months, and ORR 13% [3,36] compared to the historical benchmark of 2.0 months, 7.1 months, and 1.6% respectively for similar patients treated with approved standard of care. Two pts achieved a partial response and 11 pts had stable disease for an overall disease control rate of 87% (13/15 [64%,97%]). This compares favorably to the historical control 44%. 16 pts reported 1 or more treatment-emergent adverse events (AEs), most commonly neutrophil count decreased (n=9, 52.9%), fatigue (n=6, 35.3%), pyrexia (n=4, 23.5%), platelet count decreased (n=4, 23.5%) and decreased appetite (n=4, 23.5%). Most of the AEs were grade (G) 1-2. 12 G3 AEs were observed (mostly neutrophil count decreased [8]). Conclusion: BOLD-100 plus FOLFOX is an active and well-tolerated treatment regimen in the heavily pre-treated metastatic CRC trial population. There were no new safety signals. PK and PD data are forthcoming. The preliminary mPFS, mOS, ORR and DCR data in this interim analysis demonstrate significant improvement over the currently available approved therapies. Citation Format: Jennifer Spratlin, Grainne O'Kane, Do-Youn Oh, Sun Young Rha, Elaine McWhirter, Elena Elimova, Petr Kavan, Moon Ki Choi, Dae Won Kim, Rachel Goodwin, J Randolph Hecht, Seung Tae Kim, Dong-Hoe Koo, Khalif Halani, E Russell McAllister, Michelle Jones, Malcolm Snow, Yasmin Lemmerick, Gonzalo Spera, Jim Pankovich. BOLD-100-001 (TRIO039): a phase 1b/2a dose-escalation study of BOLD-100 in combination with FOLFOX chemotherapy in patients with pre-treated advanced colorectal cancer: interim efficacy, safety and tolerability analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT149.