Adult Phase I Clinical Trial
Phase I clinical trial of p28 in adult patients with metastatic solid tumors expressing p53
We completed a first-in-class, first-in-human Phase I clinical trial of our lead compound, p28 (NSC7451040) in patients with recurrent, refractory and progressive solid tumors. A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3+3 dose escalation design until either a grade 3-related adverse event occurred or the maximum tolerated dose (MTD) was reached. Single-dose and steady-state serum pharmacokinetics were characterized.
No patients exhibited any dose-limiting toxicities (DLTs), significant adverse events or exhibited an immune response (IgG) to p28. Seven patients demonstrated stable disease, three a partial response, and one a complete response (Range Alive: 238-256 weeks (>4.5 years), Median 247 weeks (4.8 years). Range DOD: 7-152 weeks).
p28 is well tolerated in patients with recurrent, refractory, and progressive solid tumors. Pharmacokinetics data suggest that in adults a dose of 30 mg/kg can be administered for a prolonged period without toxicity and possibly with considerable clinical efficacy. Evidence of anti-tumor activity indicates a highly favorable therapeutic index and demonstrates proof of concept for this new class of non-HDM2-mediated peptide inhibitors of p53 ubiquitination.