Gynaecological Cancers (Systemic Therapy and Clinical Trials) Group

Our mission is to improve the outcomes of women with gynaecological cancers. We contribute to the achievement of this goal by collaborating nationally and internationally on clinical studies. We work closely with laboratory scientists to help take forward pre-clinical findings through to patients in the clinic. The interaction between the clinic and lab is key to understanding mechanisms of resistance and identifying patients most likely to benefit from therapies.

We also aim to address important clinical and biological questions in retrospective analyses including patients treated at The Royal Marsden NHS Foundation Trust. This can be very useful to enhance our understanding of the behaviour of rare gynaecological cancers.

In addition to developing new systemic therapy options, our group is focusing on research to help improve the patient experience while undergoing cancer treatment.

We work closely with ICR laboratories and the Drug Development Unit to help take preclinical findings and early-phase clinical trials forward in gynaecological cancers. Below is a list of examples of current trials,

The OCTOPUS trial (Chief Investigator Dr Susana Banerjee) is a multicentre, randomised, phase II umbrella trial of weekly Paclitaxel +/- novel agents in platinum-resistant ovarian cancer. The first arm (vistusertib, dual mTORC1/2 inhibitor), based on results of the TAX-TORC trial and preclinical work from Prof Banerji’s laboratory involves a translational research collaboration with Professor Udai Banerji (ICR) and Professor Iain McNeish (Imperial).

The ATARI/ENGOTGyn1 trial (ICR-sponsored, Chief Investigator Professor Susana Banerjee, ICR-CTSU) is an international (ENGOT/GCIG/NCRI led), multi-centre proof of concept study in clear cell carcinoma and other rare gynaecological cancers based on preclinical studies from Professor Chris Lord’s group. It is the first trial selecting treatment (ATR inhibitor (AZD6738, ceralasertib) alone or in combination with the PARP inhibitor, olaparib) based on ARID1A status. Additional arms to open in 2023 assesses the combination of ceralasertib with the PD-L1 inhibitor, durvalumab in prior immunotherapy treated endometrial cancer. The translational programme collaboration involves Professor Chris Lord, Dr Rachael Natrajan's groups, Centre for Molecular Pathology, Centre for Translational Immunotherapy and Royal Marsden Gynaecology Unit Pathology groups.

ENGOTov60/GOG3052/RAMP201 (Global Lead Professor Susana Banerjee) is an international phase 2, randomised, clinical trial designed to evaluate the efficacy and safety of VS-6766 (RAF/MEK inhibitor) vs VS-6766 in combination with defactinib (FAK inhibitor) in low grade serous ovarian carcinoma (LGSOC) according to KRAS mutation status. It is based on the results of the ICR-sponsored phase I FRAME trial and the combination has received FDA Breakthrough Therapy Designation for recurrent LGSOC.

The ENGOT/Gyn5 trial (Global Lead Professor Susana Banerjee), due to open in 2023, assesses the clinical activity of NXP800, an innovative, first-in-class HSF1 pathway inhibitor, discovered by Prof Workman’s group at the ICR which shows promising activity in preclinical models of ARID1A mutant ovarian cancer and is currently in phase I development (Prof Banerji).

Our group collaborates with Professor Lord’s group and others to address PARP inhibitor resistance. Our translational research programme includes samples from MONITOR-UK (Chief Investigator Professor Susana Banerjee), a real-world, multicentre trial of niraparib in ovarian cancer and also the Biomarkers in Gynaecological Cancer Study.

The SOPRANO trial (Chief Investigator Professor Susana Banerjee, ICR-sponsored, ICR-CTSU), planned to open in 2023, evaluates stereotactic radiotherapy (followed by observation or rechallenge with a PARP inhibitor) for oligometastatic relapse post PARP inhibitor therapy in ovarian cancer.

The FAIR-O trial (funded by Wellbeing of Women, Royal Marsden sponsored) is the first UK study to assess geriatric assessment and protocol-led interventions in the oncology clinics for women with ovarian cancer over the age of 70. This multi-centre study will also look at sarcopenia and biomarkers and is based on the work from Dr Lucy Dumas’ MD (Res) project (ICR fellow MD 2021, primary supervisor Susana Banerjee).