PYNNACLE phase II clinical trial protocol: rezatapopt (PC14586) monotherapy in advanced or metastatic solid tumors with a TP53 Y220C mutation Journal Article
| Authors: | Schram, A. M.; Fellous, M.; LeDuke, K.; Schmid, A.; Dumbrava, E. E. |
| Article Title: | PYNNACLE phase II clinical trial protocol: rezatapopt (PC14586) monotherapy in advanced or metastatic solid tumors with a TP53 Y220C mutation |
| Abstract: | <p>Rezatapopt is an investigational, first-in-class p53 reactivator specific to the TP53 Y220C mutation that works to stabilize and restore wild-type p53 conformation and tumor suppressor function. PYNNACLE (NCT04585750) is a phase I/II, single-arm, multicenter, clinical trial assessing rezatapopt in patients with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation. PYNNACLE phase II is currently enrolling (target enrollment is similar to 114 patients across five cohorts defined by tumor type) and assesses rezatapopt at the recommended phase II dose. Eligible patients are aged >= 18 years (at all global sites except >= 21 years in Singapore and >= 19 years in South Korea) or 12-17 years if weighing >= 40 kg (in Australia, South Korea [12-18 years], and USA only), with locally advanced or metastatic solid tumors harboring a TP53 Y220C mutation and that are KRAS wild-type. Patients must have received >= 1 prior line of systemic therapy or be ineligible for standard of care and have measurable disease at baseline. Patients with KRAS single nucleotide variants are excluded. Eligible patients receive oral rezatapopt at 2000 mg, once daily, taken with food, for continuous 21-day cycles. The primary endpoint is the overall response rate assessed by blinded independent central review.</p><p>PLAIN LANGUAGE SUMMARY</p><p>Rezatapopt is a new drug being tested in clinical trials to help treat people with advanced solid tumors that have a specific mutation (Y220C) of the TP53 gene. Rezatapopt is designed to target p53 proteins that do not function properly due to this mutation. This helps to restore the normal function of the p53 proteins, so they can work to stop cancer cells from growing and spreading. In the phase II PYNNACLE clinical trial, described here, the effectiveness and safety of rezatapopt will be tested in patients with different types of advanced cancer with a TP53 Y220C mutation and who do not have a single nucleotide variant mutation in the KRAS gene (KRAS wild-type). This trial is for adults (18 years of age and older) and teenagers (in selected countries) who have already tried other treatments for their cancer that did not work or have stopped working, or for those who are not eligible to have the standard treatments that are available. To join this clinical trial, patients need to have solid tumors that can be measured. Participants will take rezatapopt once a day with food, over 21-day cycles. Doctors will closely monitor how the cancer responds to the rezatapopt treatment and will check for any side effects. This phase II clinical trial is already underway in several countries and will include around 114 patients.</p> |
| Keywords: | clinical trial; p53; solid tumors; phase 2; mutant p53; cancer; single-arm; rezatapopt; tp53 y220c; reactivator |
| Journal Title: | Future Oncology |
| ISSN: | 1479-6694 |
| Publisher: | Future Medicine |
| Publication status: | Online ahead of print |
| Date Published: | 2025-01-01 |
| Online Publication Date: | 2025-01-01 |
| Language: | English |
| ACCESSION: | WOS:001571396500001 |
| DOI: | 10.1080/14796694.2025.2557176 |
| PROVIDER: | wos |
| Notes: | Article; Early Access -- Source: Wos |
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