NTS071-101: A phase 1/2a study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of NTS071 in patients with advanced solid tumors harboring a TP53 Y220C mutation
Presenter: Qiancheng Shen, PhD Session: Phase I and Phase II Clinical Trials in Progress Time: 4/21/2026 2:00:00 PM → 4/21/2026 5:00:00 PM
Authors
Qiancheng Shen , Yan Xu , Yinqun Wu , Shuhan Shen , Guoqiang Zhou Nutshell Therapeutics (Shanghai) Co., LTD., Shanghai, China
Abstract
Background: The TP53 gene encodes a tumor suppressor that binds to DNA and transcriptionally activates a network of target genes responsible for cell-cycle checkpoint, apoptosis, DNA repair, and other cellular processes. The normal function of p53 protein is inactivated by different mutations in about half of all cancer cases. Y220C is a prevalent TP53 missense mutation affecting approximately 100,000 new cancer cases per year worldwide. NTS071 is a novel small molecule designed to selectively bind and stabilize TP53 Y220C mutant protein, restoring wild type p53 function. In preclinical studies, NTS071 has demonstrated superior in vitro potency, favorable ADME/T profile, and enhanced in vivo antitumor efficacy versus PC14586 (an investigational drug with the same targeting mechanism). No therapies targeting TP53 Y220C are currently approved, highlighting the significant unmet medical need. Methods: NTS071-101 is a first-in-human, open-label, multi-center phase 1/2a study designed for patients with TP53 Y220C-mutated advanced solid tumors who have failed standard therapies. The study comprises two parts: phase 1 (dose escalation with backfilling) and phase 2a (dose optimization). Phase 1 employs an accelerated titration design for 100 and 200 mg dose levels, followed by Bayesian Optimal Interval (BOIN) design with backfilling. The planned dose levels for the dose escalation stage include 100, 200, 400, 800, 1200, 1600, and 2000 mg, administered orally once daily (QD) in 21‑day treatment cycles. The primary objectives of phase 1 are to evaluate the safety and tolerability, and to determine the Maximum Tolerated Dose (MTD). Secondary objectives include pharmacokinetic (PK) profiling and preliminary efficacy assessment. The phase 2a study aims to evaluate the preliminary clinical efficacy of NTS071. Secondary objectives include further characterization of its efficacy profile, determination of the Recommended Phase 2b Dose(s) (RP2bD), assessment of safety, and PK profiling. Exploratory objectives are to evaluate the correlations between NTS071’s pharmacodynamic profiles, efficacy outcomes, and relevant biomarkers. Summary: The first-in-human trial of NTS071 marks a critical milestone in advancing such precision oncology therapies for those patients with limited treatment options and poor prognosis. The first patient for NTS071-101 enrolled in August 2025, with active recruitment continuing in both the U.S. and China.
Disclosure
Q. Shen, None.. Y. Xu, None.. Y. Wu, None.. S. Shen, None.. G. Zhou, None.
Cited in
Control: 9975 · Presentation Id: 12220 · Meeting 21436