drugset / Trial / NCT04585750
The Evaluation of PC14586 in Patients With Advanced Solid Tumors Harboring a TP53 Y220C Mutation (PYNNACLE)
Non-randomizedParallel-groupOpen-labelTreatment
Summary
The Phase 2 monotherapy portion of this study is currently enrolling and will evaluate the efficacy and safety of PC14586 (INN rezatapopt) in participants with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. The Phase 1 portion of the study will assess the safety, tolerability and preliminary efficacy of multiple dose levels of rezatapopt as monotherapy and in Phase 1b in combination with pembrolizumab.
Timeline
- Start
- 2020-10-29
- Primary completion
- 2026-08-15
- Completion
- 2027-12-31
Publications
- Dumbrava EE, Shapiro GI, Parikh AR, Johnson ML, Tolcher AW, Thompson JA, El-Khoueiry AB, Vandross AL, Kummar S, Shepard DR, LeDuke K, Sheehan L, Alland L, Haque A, Jalota D, Fellous M, Schram AM. Phase 1 Study of Rezatapopt, a p53 Reactivator, in TP53 Y220C-Mutated Tumors. N Engl J Med. 2026 Feb 26;394(9):872-883. doi: 10.1056/NEJMoa2508820.
- Schram AM, Fellous M, LeDuke K, Schmid A, Dumbrava EE. PYNNACLE phase II clinical trial protocol: rezatapopt (PC14586) monotherapy in advanced or metastatic solid tumors with a TP53 Y220C mutation. Future Oncol. 2025 Oct;21(24):3159-3166. doi: 10.1080/14796694.2025.2557176. Epub 2025 Sep 11.
- Papavassiliou KA, Vassiliou AG, Papavassiliou AG. Rezatapopt: A promising small-molecule "refolder" specific for TP53Y220C mutant tumors. Neoplasia. 2025 Sep;67:101201. doi: 10.1016/j.neo.2025.101201. Epub 2025 Jun 20.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | rezatapopt | Small molecule | 150 mg | Oral |
| Subject | rezatapopt | Small molecule | 300 mg | Oral |
| Subject | rezatapopt | Small molecule | 600 mg | Oral |
| Subject | rezatapopt | Small molecule | 1150 mg | Oral |
| Subject | rezatapopt | Small molecule | 1500 mg | Oral |
| Subject | rezatapopt | Small molecule | 2000 mg | Oral |
| Subject | rezatapopt | Small molecule | 2500 mg | Oral |
| Background | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |