Bold Therapeutics' Bold-100 shows lower neuropathy rates in Phase I/II FOLFOX combination trial

Bold Therapeutics reported that BOLD-100, its ruthenium-based anticancer agent, was associated with substantially lower rates of oxaliplatin-induced peripheral neuropathy in patients receiving FOLFOX chemotherapy across three advanced gastrointestinal cancer types, adding a potential tolerability dimension to a drug already in Phase II development for efficacy.

The BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours trial (NCT04421820) is a global Phase I/II randomized controlled study enrolling patients with advanced gastrointestinal cancers across sites in Canada, the EU, and South Korea.

Compared to historical benchmarks for FOLFOX alone, any-grade neuropathy rates in patients receiving BOLD-100 plus FOLFOX were 14% versus a 53% benchmark in metastatic colorectal cancer, 19% versus 63% in gastric cancer, and 35% versus 58% in biliary tract cancer. The company did not disclose patient numbers for each subgroup, and the comparisons are against historical controls rather than a concurrent randomized arm, which limits interpretation. No formal safety analysis was presented alongside these figures.

The neuropathy data are being presented at the American Association for Cancer Research Annual Meeting on April 21 alongside in vivo and in vitro preclinical modelling intended to provide mechanistic context for the observed clinical signal.

BOLD-100 is a first-in-class ruthenium-based small molecule, distinct from platinum-based agents such as oxaliplatin. Trial evidence links it to downregulation of GRP78, a protein associated with endoplasmic reticulum stress responses in tumor cells, though that target assignment remains incompletely validated. Oxaliplatin, the platinum component of FOLFOX, causes peripheral neuropathy through DNA adduct formation and crosslinking; the mechanism by which a ruthenium compound might attenuate this toxicity is not established from the press release alone and will be addressed in the AACR preclinical presentation. Cross-trial comparisons are limited by differences in patient populations, follow-up duration, and grading criteria, and the neuropathy figures reported here should not be interpreted as equivalent to prospectively powered endpoint data.

The ongoing Phase II randomized trial includes quality-of-life questionnaires focused on neuroprotective outcomes alongside its primary anticancer endpoints, which suggests the company is building a prospective dataset to support the clinical observation reported here. Full data from that trial, including formal efficacy readouts and patient-reported neuropathy assessments, have not yet been disclosed.

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