Abstract 44P
Background
BOLD-100 is a novel ruthenium-based small molecule targeting GRP78 to modulate the unfolded protein response and generate reactive oxygen species leading to DNA damage and cell cycle arrest. This dual action triggers cell death across a spectrum of cancer types, including those resistant to current treatments.
Methods
This prospective, phase 2 study evaluates BOLD-100 + FOLFOX in pts with metastatic colorectal cancer (mCRC) (n=38) who have received prior standard treatment, including FOLFOX or CAPOX. Pts received 625 mg/m2 of BOLD-100 + FOLFOX on day 1 of each 14-day cycle and treated until progressive disease or unacceptable toxicity. The primary objective is to evaluate PFS, OS, and ORR in treated patients. Disease Control Rate (DCR) was also determined.
Results
As of 14Mar24, 38 advanced mCRC pts relapsed or refractory to at least two lines of therapy were treated. Median age was 62 years (range 40-78), 53% women, all pts were ECOG 0 (26%) or 1 (74%). Pts had a median of 4 prior systemic therapies [range 2-8]. All but one patient had stage IV disease. Patients received a median of 6 cycles of BOLD-100 + FOLFOX [range 1-18]. Median PFS was 4.2 [95% credible interval 3.0, 6.0] months, median OS 8.3 [5.7,13] months, ORR 10% [3,24] and DCR 77% [61,89] in 31 evaluable pts. Three pts achieved a partial response; 2 pts had target tumor lesion decreases between 20-29%. Treatment was well tolerated. Of the 38 treated pts, 35 had 1 or more treatment-related adverse events (AEs), most common neutropenia (n=18, 47%), nausea (n=16, 42%), vomiting (n=8, 21%), fatigue (n=8, 21%), infusion related reaction (n=8, 21%), and pruritus (n=6, 16%). Most related AEs were grade (G) 1-2. Sixteen pts (42%) had G3/4 neutropenia. Despite previous oxaliplatin treatment, fewer than 5% of pts reported peripheral neuropathy; those reported were G1/2.
Conclusions
There remains an unmet need for improved treatment options for patients with mCRC. BOLD-100 + FOLFOX is an active and well-tolerated treatment despite a heavily pretreated population. The mPFS, mOS, ORR and DCR data demonstrate clinical benefit with minimal neuropathy or significant toxicities. This promising treatment combination should be further studied.
Clinical trial identification
NCT04421820.
Legal entity responsible for the study
Bold Therapeutics Inc.
Funding
Bold Therapeutics Inc.
Disclosure
D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD, LG Chem, Astellas, AbbVie, J-Pharma, Mirati Therapeutics, Eutilex, Moderna, Idience; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD, Daiichi Sankyo, Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Indivumed, AstraZeneca; Financial Interests, Other, Durg supply for clinical trial: Merck; Financial Interests, Institutional, Invited Speaker, Drug supply for clincal trial: MSD; Financial Interests, Institutional, Invited Speaker, drug supply for clinical trial: zy,meworks; Financial Interests, Institutional, Invited Speaker, drug supply for clincial trial: BeiGene; Financial Interests, Invited Speaker: Roche. E. Elimova: Financial Interests, Personal, Invited Speaker: Roche, Daiichi; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: BeiGene, Signatera, AbbVie, Astellas, Viracta Tx; Financial Interests, Institutional, Invited Speaker, Institution recieves: Jazz; Financial Interests, Institutional, Invited Speaker: Jazz, Zymeworks, Amgen, AstraZeneca, BMS; Other, A family member employed by Merck Vaccines: Merck. R.A. Goodwin: Financial Interests, Personal, Advisory Board, AdBoard and Speaker: AAA/Novartis; Financial Interests, Personal, Advisory Board, Advisory Board and Speaker: Ipsen, Pfizer, Amgen, AstraZeneca, Eisai, BMS, Astellas; Financial Interests, Personal, Advisory Board, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker, Advisory Board and Speaker: Merck, Taiho; Non-Financial Interests, Leadership Role, Scientific and Medical Advisory Board Executive: CNET; Non-Financial Interests, Leadership Role, Co-chair of Colon Disease Oriented GroupIND/ GI Liason: CCTG; Non-Financial Interests, Personal, Other, Travel Grant: Ipsen; Non-Financial Interests, Institutional, Other, Independent Grant: Ipsen, Pfixer. K. Halani: Financial Interests, Personal, Full or part-time Employment: Emmes Canada. R. McAllister, M. Jones, M.D. Snow: Financial Interests, Personal, Full or part-time Employment: Bold Therapeutics Inc.; Financial Interests, Personal, Stocks/Shares: Bold Therapeutics Inc. Y. Lemmerick, G. Spera: Financial Interests, Personal, Full or part-time Employment: Translational Research In Oncology. J. Pankovich: Financial Interests, Personal, Full or part-time Employment: Bold Therapeutics Inc. All other authors have declared no conflicts of interest.