Abstract CT147: High dose intravenous ascorbate with chemotherapy as NAC for muscle invasive cisplatin ineligible bladder cancer patients

Abstract Purpose: Neoadjuvant cisplatin-based chemotherapy (NAC) is considered the standard of care (SOC) for patients with muscle-invasive bladder cancer (MIBC). However, ∼50% of patients are cisplatin ineligible (CI) and often proceed directly to surgery. Other regimen such as gemcitabine and carboplatin has limited success in this setting. High-dose intravenous ascorbate (IVC) has been shown to have anti-cancer efficacy in pre-clinical and clinical studies, and to improve efficacy of carboplatin and gemcitabine-based therapy in other cancer models. Here we initiated a phase Ib/IIa trial to evaluate IVC with gemcitabine/carboplatin (Gem/Carbo) as NAC in CI-MIBC patients (NCT04046094). Patients and Methods: Patients with newly diagnosed CI-MIBC received single cycle Gem (1000 mg/m2 D1, 8) / Carbo (AUC 5 day 1) and IVC (25-125g titrated to 350-400 mg/dL blood concentrations, and then 2x per week for 21 days) followed by definitive cystectomy. The primary outcome was pathological downstaging (<ypT2N0Mx) at cystectomy. Patient-reported quality of life (QOL) was assessed by FACT-BI at enrollment, end of treatment, and 6 weeks after cystectomy. Results: Sixteen participants were enrolled, with 12 completing the protocol; mean age was 76. Pathological downstaging was present in 4 (33%), with 3/4 patients having a pathologic complete response (pCR, ypT0N0Mx), and 1 with residual ypTisN0Mx only. Of note, 1 CR was seen in a patient with locally advanced plasmacytoid variant. Treatment was well tolerated with minimal treatment related AE/SAEs. At a mean follow-up of 32.3 months (SD 18.9, range 6.6 - 63.8), 4 patients without response recurred and died of disease, 3 with response have recurred with one passing from disease. QOL FACT-Bl showed no decline from baseline to end of treatment (EOT) to 6 weeks post cystectomy. Conclusions: Neoadjuvant, single cycle Gem/Carbo + IVC was well tolerated and had significant activity in a difficult to treat population of CI-MIBC, offering an alternative for patients who otherwise are cisplatin-ineligible and may not realize the benefit of NAC. Response rate (RR) is comparable to SOC in this early Phase trial. Larger trials are warranted to confirm these findings and identify biomarkers of response. Citation Format: Qi Chen, John Taylor, Rahul Parikh, Ben Woolbright, Jeanne Drisko. High dose intravenous ascorbate with chemotherapy as NAC for muscle invasive cisplatin ineligible bladder cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT147.