"To demonstrate the potential utility of ONC201 in combination...

"To demonstrate the potential utility of ONC201 in combination with paxalisib, we report two recent DIPG case studies of patients that received both ONC201 and paxalisib through compassionate access. These patients underwent radiographic analysis according to response assessment in pediatric neuro-oncology (RAPNO). The first is a 6-year-old patient diagnosed in March, 2021, harboring H3.1K27M, ACVR1, and PIK3R1 mutant DIPG identified following biopsy (Fig. 6A). At diagnosis, a diffuse pontine lesion was identified (Fig. 6B and C, tumor area 1,554 mm²). The patient received 54 Gy of RT delivered in 30 fractions of 1.8 Gy in the 1 to 3 months following diagnosis. After RT MRI indicated a tumor reduction of 38.1% compared with diagnosis (Fig. 6B and D; tumor area 962 mm²). The patient began the combination treatment of ONC201 (15 mg/kg once a week) and paxalisib (27 mg/m² daily) 7 weeks following the after RT scan, corresponding to 5 months after diagnosis. Tumor size remained relatively stable over the next consecutive MRIs (Fig. 6E and F, tumor area = 1,156 and 1,224 mm², respectively). Encouragingly, 9 months after diagnosis, a substantial 62.1% decrease in tumor area based on T2-weighted images was recorded from the previous MRI, representing a 70.1% reduction compared with diagnosis and 51.8% reduction compared with after RT (Fig. 6B and G; tumor area = 464 mm²), showing a partial response. Furthermore, 12 months after diagnosis, 8 months into the ONC201 and paxalisib combination, the tumor had reduced by 80.3% and 68.2%, compared with diagnosis and after RT, respectively (Fig. 6B and H; tumor area = 306 mm²). Clinically, 24 months after diagnosis, the tumor remains stable (Fig. 6I) and the patient continues to do well, experiencing continued reduction in DIPG-associated clinical symptoms, and has returned to school. Intermittent toxicities during treatment included grade II mucositis during the initial few months on the combination, which responded well to dexamethasone mouthwash."
https://aacrjournals.org/cancerres/.../ONC201-in-Combination-with-Paxalisib-for-the