Oncology Conference update 

Update from ESGO 2026 – PYNNACLE Phase 2 study: Interim results from the ovarian cancer cohort

Clinical insights and expert discussion

Prof. Domenica Lorusso

Prof. Domenica Lorusso
Prof. Jean-Sebastien Frenel

Prof. Jean-Sebastien Frenel
Publication Date

Mar 2026

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Profs Domenica Lorusso and Jean-Sebastien Frenel share expert insights on the PYNNACLE Phase 2 interim analysis at ESGO 2026. The PYNNACLE study evaluates rezatapopt*, a first-in-class p53 reactivator, in TP53 Y220C–mutant advanced solid tumours, including ovarian cancer.

 

In this video, the experts discuss: 

  • TP53, the Y220C variant, and the rationale for mutant p53 reactivation 
  • Study overview and practice implications, spotlighting ovarian cancer 
  • Testing strategies for early and accurate patient identification 

 

Clinical takeaways

  • Rezatapopt is a first-in-class investigational p53 reactivator that selectively binds to the mutated p53 Y220C protein, stabilising its structure to restore wild-type tumour suppressor activity   
  • Rezatapopt demonstrates rapid, durable and broad antitumour activity in heavily pretreated patients with TP53 Y220C-mutated advanced ovarian cancer, where effective targeted therapies and biomarkers are limited  
  • Looking ahead, it will be important to prioritise early and accurate identification through up-front comprehensive genomic profiling using NGS with TP53 gene coverage. Tissue is preferred; when tissue is limited, selected ctDNA assays capable of excluding CHIP may be used 

 

*Rezatapopt is an investigational agent which is not approved by a regulatory agency

  • Educate on the role of TP53 as a tumour suppressor gene, its mutation in cancer, and the significance of the Y220C variant​
  • Highlight the importance of treating cancers based on genomic mutations​
  • Emphasise the need for genomic testing to identify patients with the TP53 Y220C mutation​
  • Educate clinicians on the ongoing clinical trials, such as the PYNNACLE trial

Prof. Domenica "Ketta" Lorusso obtained her degree in Medicine and Surgery in 1995, her residency in Obstetrics and Gynecology in 1999 and her PhD in Obstetrics and Gynecology in 2003. She is currently Associate Professor of Obstetrics and Gynecology at the Catholic University of Rome and responsible for clinical research at Fondazione Policlinico Gemelli IRCCS.

She is an active member of the European Network of Gynaecological Oncological Trial groups (ENGOT), where she leads the Gynecological Cancer Academy (since 2020). Dr Lorusso is a member of the Board of Directors of the Gynecologic Cancer InterGroup (GCIG), where she is the past chair of the Endometrial Cancer Committee and the Nomination and Meeting Committee. Currently, she is a member of the ESGO Council and scientific coordinator of the ESMO Gynaecological Cancers Congress. She is involved in preclinical and clinical research in gynaecological cancer, and she is the author of more than 250 papers on gynaecological cancers. Her work has hugely contributed to improving the quality of care and clinical outcome and to reducing the toxicity of treatments in women with advanced gynaecological malignancies.

Prof. Domenica Lorusso has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

MSD, GSK, Novartis, Clovis Oncology, AstraZeneca, Eisai, PharmaMar, ImmunoGen, Genmab

Prof. Frenel is a Medical Oncologist at the Institut de Cancerologie de L’Ouest in Nantes France. He is a professor of medicine at Nantes University and a member of the Board of the GINECO group.

Prof. Jean-Sebastien Frenel has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Astra Zeneca, GSK, Esai, MSD, Lilly, Pfizer, Novartis, Daichi Sankyon, Seagen, ABBVIE, ROCHE, Pharma End, Boehringer
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Profs Domenica Lorusso and Jean-Sebastien Frenel share expert insights on the PYNNACLE Phase 2 interim analysis at ESGO 2026. The PYNNACLE study evaluates rezatapopt*, a first-in-class p53 reactivator, in TP53 Y220C–mutant advanced solid tumours, including ovarian cancer.

 

In this video, the experts discuss: 

  • TP53, the Y220C variant, and the rationale for mutant p53 reactivation 
  • Study overview and practice implications, spotlighting ovarian cancer 
  • Testing strategies for early and accurate patient identification 

 

Clinical takeaways

  • Rezatapopt is a first-in-class investigational p53 reactivator that selectively binds to the mutated p53 Y220C protein, stabilising its structure to restore wild-type tumour suppressor activity   
  • Rezatapopt demonstrates rapid, durable and broad antitumour activity in heavily pretreated patients with TP53 Y220C-mutated advanced ovarian cancer, where effective targeted therapies and biomarkers are limited  
  • Looking ahead, it will be important to prioritise early and accurate identification through up-front comprehensive genomic profiling using NGS with TP53 gene coverage. Tissue is preferred; when tissue is limited, selected ctDNA assays capable of excluding CHIP may be used 

 

*Rezatapopt is an investigational agent which is not approved by a regulatory agency

  • Educate on the role of TP53 as a tumour suppressor gene, its mutation in cancer, and the significance of the Y220C variant​
  • Highlight the importance of treating cancers based on genomic mutations​
  • Emphasise the need for genomic testing to identify patients with the TP53 Y220C mutation​
  • Educate clinicians on the ongoing clinical trials, such as the PYNNACLE trial

Prof. Frenel is a Medical Oncologist at the Institut de Cancerologie de L’Ouest in Nantes France. He is a professor of medicine at Nantes University and a member of the Board of the GINECO group.

Prof. Jean-Sebastien Frenel has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

Astra Zeneca, GSK, Esai, MSD, Lilly, Pfizer, Novartis, Daichi Sankyon, Seagen, ABBVIE, ROCHE, Pharma End, Boehringer

Prof. Domenica "Ketta" Lorusso obtained her degree in Medicine and Surgery in 1995, her residency in Obstetrics and Gynecology in 1999 and her PhD in Obstetrics and Gynecology in 2003. She is currently Associate Professor of Obstetrics and Gynecology at the Catholic University of Rome and responsible for clinical research at Fondazione Policlinico Gemelli IRCCS.

She is an active member of the European Network of Gynaecological Oncological Trial groups (ENGOT), where she leads the Gynecological Cancer Academy (since 2020). Dr Lorusso is a member of the Board of Directors of the Gynecologic Cancer InterGroup (GCIG), where she is the past chair of the Endometrial Cancer Committee and the Nomination and Meeting Committee. Currently, she is a member of the ESGO Council and scientific coordinator of the ESMO Gynaecological Cancers Congress. She is involved in preclinical and clinical research in gynaecological cancer, and she is the author of more than 250 papers on gynaecological cancers. Her work has hugely contributed to improving the quality of care and clinical outcome and to reducing the toxicity of treatments in women with advanced gynaecological malignancies.

Prof. Domenica Lorusso has received financial support/sponsorship for research support, consultation, or speaker fees from the following companies:

MSD, GSK, Novartis, Clovis Oncology, AstraZeneca, Eisai, PharmaMar, ImmunoGen, Genmab
pdf Download Poster - PDF clock
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