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Targeting TP53 Mutations in Advanced Solid Tumors
Volume 1
Issue 1

Kummar on the Investigation of Rezatapopt in TP53 Y220C–Mutated Advanced Solid Tumors

Dr Kummar discusses the significance of targeting TP53 Y220C in solid tumors and early data reported with rezatapopt in TP53 Y220C–mutant solid tumors.

Welcome to OncLive On Air®! I’m your host today, Courtney Flaherty.

OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, sponsored by PMV Pharmaceuticals, we had the pleasure of speaking with Shivaani Kummar, MBBS, FACP, about the ongoing investigation of the first-in-class p53 reactivator rezatapopt (PC14586) for patients with TP53 Y220C–mutated advanced solid tumors. Dr Kummar is the Margaret and Lester DeArmond Endowed Chair of Cancer Research, professor, and division head in the Division of Hematology/Medical Oncology at the Oregon Health & Science University School of Medicine in Portland. She is also the codirector of the Center for Experimental Therapeutics and the co-deputy director of the Knight Cancer Institute.

The development of tumor-agnostic agents, such as rezatapopt, is revolutionizing cancer treatment by focusing on specific molecular targets across different tumor types rather than histologic classification. Rezatapopt has activity in advanced solid tumors harboring this mutation, particularly ovarian, breast, lung, and endometrial cancers, with notable response rates and manageable adverse effects.

Updated results from the phase 1/2 PYNNACLE trial (NCT04585750) revealed a 38% confirmed overall response rate (ORR) with rezatapopt monotherapy administered at the recommended phase 2 dose (RP2D) of 2000 mg daily in patients with TP53 Y220C–mutant, KRAS wild-type tumors (n = 16). Within the ovarian cancer cohort, partial responses were achieved by 7 of the 15 patients with measurable disease at baseline, and 7 patients achieved stable disease. These early data support further investigation of rezatapopt in the phase 2 segment of the trial, which is currently assessing the efficacy of rezatapopt at the RP2D across various cohorts of patients with TP53 Y220C–mutant, KRAS wild-type solid tumors.

In our exclusive interview, Dr Kummar discussed the significance of targeting TP53 Y220C in solid tumors, early efficacy and safety data reported with rezatapopt in TP53 Y220C–mutant solid tumors, and directions for future development of TP53-directed drugs both alone and in combination regimens.


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