Abstract LB432: Clinical-stage anticancer agent BOLD-100 demonstrates protective effects against oxaliplatin-induced peripheral neuropathy in an in-vivo rat model
Notice bibliographique
Résumé
Abstract BOLD-100 is a first-in-class, ruthenium-based anticancer agent in Phase 2 clinical development for advanced gastrointestinal (GI) cancers in combination with FOLFOX. Clinical results have shown that BOLD-100 combined with FOLFOX improves overall survival (OS) and progression-free survival (PFS) in patients with advanced colon, gastric, and bile duct cancers. Emerging clinical evidence indicates a very well tolerated safety profile for BOLD-100 in combination with FOLFOX. While FOLFOX is a first- or second-line standard-of-care therapy for GI cancers, its clinical utility is limited by the induction of acute and chronic peripheral neuropathies. Notably, in clinical trial BOLD-100-001 (NCT04421820), an unexpected reduction in oxaliplatin-induced peripheral neuropathy (OIPN) was observed. In patients treated with BOLD-100 and FOLFOX, any-grade neuropathy was reduced compared to benchmark FOLFOX-alone patients: mCRC (14% vs. 53%), BTC (36% vs. 67%), and GC (19% vs. 63%). However, translational and preclinical investigations into the neuroprotective effects of BOLD-100 are necessary. To assess BOLD-100’s neuroprotective effects in an in-vivo model, Sprague-Dawley (SD) rats received intraperitoneal low-dose oxaliplatin (0.5 mg/kg) or high-dose oxaliplatin (1.5 mg/kg) twice weekly until Day 17. Concurrently, BOLD-100 (40 mg/kg) or vehicle (10 mL/kg) was administered via slow IV bolus (∼30 seconds) twice weekly. Cold allodynia was measured using the acetone spray test at baseline (Day -1) and 0.5 hours post-oxaliplatin administration on each dosing day. Rats treated only with oxaliplatin developed significant cold allodynia by Day 7 (high dose) and Day 10 (low dose), whereas animals co-treated with BOLD-100 substantially prevented the development of peripheral neuropathy at both oxaliplatin doses. In the high-dose model, significant attenuation of OIPN was observed as early as Day 7 (p = 0.02), with highly significant reductions from Day 10 (p = 0.0009) to Day 21 (p < 0.000001). In the low-dose model, a complete attenuation of OIPN was observed from Day 10 (p = 0.01) to Day 21 (p = 0.00007). To elucidate possible mechanisms, we used plasma samples from patients in clinical trial BOLD-100-001, we observed a strong induction of multiple cytokines relevant to neuroprotective effects. Importantly, patients who developed neurotoxicity-related adverse events during the study appeared to have a reduced capacity to induce these cytokines after BOLD-100 treatment. Collectively, these findings provide strong evidence that BOLD-100 not only enhances oxaliplatin-based therapy in GI malignancies but also improves its clinical utility by markedly reducing OIPN. Ongoing clinical studies are evaluating BOLD-100’s neuroprotective benefits and its potential to enhance the therapeutic index of standard-of-care regimens for advanced GI cancers. Citation Format: Ashish Kumar, Brian Park, Malcolm Snow, Russell McAllister, Jim Pankovich, Mark Bazett. Clinical-stage anticancer agent BOLD-100 demonstrates protective effects against oxaliplatin-induced peripheral neuropathy in an in-vivo rat model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB432.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 0,001 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».