Pravitinib (carboxyamidotriazole orotate) / Tactical Therap - LARVOL DELTA

Carboxyamidotriazole orotate (CTO) with temozolomide (TMZ) for recurrent high-grade gliomas (rHGG) and in combination with TMZ/RT->TMZ in newly diagnosed glioblastoma (ndGBM): Long term follow-up of phase IB trial (AACR 2025) - "Background: CTO, an oral brain penetrant inhibitor of calcium signaling pathways was evaluated in rHGG and ndGBM. Addition of CTO to TMZ or TMZ/RT respectively was safe with no DLT. Survival in both recurrent HGG and newly diagnosed GBM patients compares favorably with historical controls. Phase 2 randomized trials are planned.Overall Survival Summary-rHGG and ndGBM: CTO vs Historical ControlsCohortStatusNPercent censoredrHGGFailed23Censored311.54%ndGBMFailed10Censored533.33%------------------------------------------------------------------------------------------------------------------Time (months)rHGG N=26%Alive#at riskndGBM N=15% Alive#at risk010026100156882292.9131247.41092.9121819.0477.492414.2368.88360051.664843.036028.72Median OSmonths 95% Ct10.5(8.0, 14.8)37.8 (20.9,51.9)------------------------------------------------------------------------------------------------------------------Group rHGGDeadTotalMedianOS(months)95% CIp-value..."

Combination therapy • Late-breaking abstract • P1 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Malignant Glioma • Oncology • Solid Tumor • EGFR • MGMT

Safety and Tolerability of Carboxyamidotriazole Orotate (CTO) in Solid Tumors or With Temodar® in Glioblastoma or Other Recurrent Malignant Gliomas or in Combination With Temodar® and Radiation Therapy for Patients With Newly Diagnosed Glioblastoma and Malignant Gliomas (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Tactical Therapeutics, Inc. | Trial completion date: Jan 2024 ➔ Jan 2026 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor

Safety and Tolerability of Carboxyamidotriazole Orotate (CTO) in Solid Tumors or With Temodar® in Glioblastoma or Other Recurrent Malignant Gliomas or in Combination With Temodar® and Radiation Therapy for Patients With Newly Diagnosed Glioblastoma and Malignant Gliomas (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Tactical Therapeutics, Inc. | Unknown status ➔ Active, not recruiting | Trial primary completion date: Jun 2018 ➔ Jan 2024

Combination therapy • Enrollment closed • Metastases • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor

Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas. (PubMed, J Clin Oncol) - "Signals of activity in cohort 1 (n = 27) included partial (n = 6) and complete (n = 1) response, including in O-methylguanine-DNA methyltransferase unmethylated and bevacizumab-refractory tumors. Gene sequencing disclosed a high rate of responses among EGFR-amplified tumors ( P = .005), with mechanisms of acquired resistance possibly involving mutations in mismatch-repair genes and/or downstream components TSC2, NF1, NF2, PTEN, and PIK3CA. Conclusion CTO can be combined safely with TMZ or chemoradiation in GBM and anaplastic gliomas, displaying favorable brain penetration and promising signals of activity in this difficult-to-treat population."

Clinical • Journal • P1 data