Research

Cancer Immune Therapy

I lead the cancer immunotherapy group at Barts with Professor Thomas Powles, overseeing clinical and translational research on immune checkpoint inhibitors and other immune strategies. The group currently runs more than 10 early clinical trials of single agent or combination cancer immunotherapy treatments, focusing on breast, genitourinary and thoracic cancers.

Predictive Epigenetics

We are now researching epigenetic 'signatures' of different cancers in order to treat patients with the right medicine for their specific disease. We focus on the role of epigenetics in therapeutic resistance. The aim is to match medicines to patients and reduce the number of patients needlessly subjected to uncomfortable side effects. During this genetic and epigenetic mapping, we also aim to find new cancer-specific targets for drug development.

Novel DNA Damage and Stability Biomarkers and Therapeutic Targets

Over the next 5 years, a variety of novel DDR and chromatin maintenance mechanisms will be validated and, in collaboration with the newly appointed Chairs in Drug Discovery and Medicinal Chemistry, potential inhibitors for synthetic lethality strategies will be identified.

Trials Targeting Therapeutic Resistance

• OPPORTUNE is a window-of-opportunity trial to assess whether the addition of the PI3K inhibitor Pictilisib increases the anti-tumour effects of short-term, preoperative treatment with the aromatase inhibitor anastrozole in ER-positive primary breast cancer. This design provides access to tumour tissue before and after treatment for comprehensive biomarker analysis thus providing critical insight into the optimal patient population and potential mechanisms of resistance.
• MANTA is an international, 4-arm randomised trial testing efficacy of the novel TORC1/2 inhibitor AZD2014 in combination with Fulvestrant relative to Fulvestrant alone or Fulvestrant and Everolimus in metastatic ER-positive breast cancer.
• PAKT is a double-bind, international randomised trial to evaluate the benefit of adding the AKT inhibitor AZD5363 to paclitaxel chemotherapy in triple-negative breast cancer.
• TORCMEK is designed to define the optimal regimen and the efficacy of the combination of the TORC1/2 inhibitor AZD2014 and the MEK inhibitor Selumetinib in triple-negative breast cancer and non-small cell lung cancer.

Two international window-of-opportunity trials that Professor Schmid leads focus on establishing the role of targeting the androgen receptor (AR) in early breast cancer, using the novel anti-androgen Enzalutamide:

• ARB1 will evaluate short-term, preoperative treatment with Enzalutamide in AR-positive, triple-negative breast cancer.
• ARB2 will investigate whether the addition of Enzalutamide increases the anti-tumour effects of short-term, preoperative treatment with the aromatase inhibitor exemestane in ER-positive primary breast cancer.

I also lead a national clinical trial that investigates whether the addition of the HSP27-targeting antisensce oligoneucleotide Apatorsen to chemotherapy can improve the outcome of patients with squamous cell lung cancers.

These trials are supported by NIHR and CRUK funding to the Barts/Brighton Experimental Cancer Medicine Centre. UK recruitment is also supported by the NIHR Cancer Research Network and the UK Experimental Cancer Medicine Centre network.

Circulating Biomarkers

Our international collaborative group studies circulating biomarkers for screening, diagnosis, patient management and surveillance of breast cancers. The programme includes:

• LERG-BC1, a prospective international biomarker study set-up in 2007 to systematically analyse circulating biomarkers in 800 patients with primary breast cancer before and immediately after primary surgery and during follow-up. Currently in analysis, first results will be presented in 2015.
• CirculER, a second international biomarkers study looks at circulating biomarker changes over time to characterise the plasticity of hormone-dependent breast cancers and therapeutic resistance development. This trial is ongoing, supported by Breast Cancer Campaign.

Other Activities

• 2014-Faculty, IMPACT Training Course
• 2012-Faculty Member, Innovators in Breast Cancer
• 2011- Scientific Advisory Board Member, Breast Cancer Campaign (ongoing)
• Member of UK NCRN Breast Cancer CSG, ongoing
• 2010- Clinical Expert for the UK National Institute for Health and Clinical Excellence (NICE), nominated by the Royal College of Physicians
• 2009- Interdisciplinary National Board, Metastatic Breast Cancer, Germany
• Chair, Imperial College Charing Cross Clinical Trials Unit (until 2010)
• 2008- International Cancer Research UK CTAAC Advisory Panel (until 2012)
• 2007- Consensus Panel, Management of Metastatic Breast Cancer, organised by the Central European Cooperative Oncology Group
• 2006- Chair, Drugs and Therapeutics Group, West London Cancer Network
• Fractional Lecturer, Postgraduate Certificate/Diploma MSc in Oncology, The Institute of Cancer Research, London UK (ongoing)
• 2005- Elected to Steering Committee, Breast Cancer Group, German Cooperative Group of Medical Oncology (AIO)
• 2004- Faculty and Lecturer, German Postgraduate Certificate/Diploma in Palliative Medicine
• Elected speaker of National Expert Commission "Off-label use in breast cancer" of the German Government Agency for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte)
• 2003- Consensus Panel, Management of Metastatic Breast Cancer, organised by the Central European Cooperative Oncology Group
• 2001-Founder and Chair of the German Interdisciplinary Working Group for Communication Training in Oncology (until 2008)

Major Funding

• 2018-2020- Roche Products Ltd, Phase II study Investigating preoperative combination strategies for immunotherapy in Breast Cancer, £1,795,833.49
• 2017-2019- AZ AstraZeneca UK Limited, TORC-MEK clinical trial, £429,569
• 2015-2020- Barts Charity, Comprehensive analysis of circulating biomarkers in breast cancer patients, £473,705
• 2014-2018- Astellas Pharma Europe Ltd, Phase II window of opportunity study of short term preoperative treatment with enzalutamide in patients with triple-negative primary breast cancer, £1,913,856
• 2014-2017- AstraZeneca UK Limited, Paclitaxel in combination with the Akt Inhibitor AZD5363 in triple-negative advanced or metastatic breast Cancer (PAKT), £1,972,925
• 2013-2018- AZ AstraZeneca UK Limited, MANTA - Fulvestrant in combination with the dual mTOR inhibitor AZD2014, £7,398,910

Recent Publications

Health-related quality of life and work productivity in UK patients with HER2-positive breast cancer: a cross-sectional study evaluating the relationships between disease and treatment stage Verrill M, Wardley AM, Retzler J et al. Health and Quality of Life Outcomes (2020) 18(7)

The development and initial evaluation of the Diarrhoea Management Diary (DMD) in patients with metastatic breast cancer Harder H, Shilling VM, May SF et al. Breast Cancer Research and Treatment (2020) 183(7) 629-638

A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER⁺ HER2^- Primary Breast Cancer Robertson JFR, Evans A, Henschen S et al. Clinical cancer research : an official journal of the American Association for Cancer Research (2020) 26(7) 4242-4249

Evaluation of pathologic complete response as a surrogate for long-term survival outcomes in triple-negative breast cancer Huang M, O'Shaughnessy J, Zhao J et al. JNCCN Journal of the National Comprehensive Cancer Network (2020) 18(7) 1096-1104

Pembrolizumab for Early Triple-Negative Breast Cancer. Reply Schmid P, Dent R, O'Shaughnessy J The New England journal of medicine (2020) 382(7) e108

Patient-reported outcomes from the phase III IMpassion130 trial of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancer Adams S, Diéras V, Barrios CH et al. Annals of Oncology (2020) 31(7) 582-589

Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study Schmid P, Salgado R, Park YH et al. Annals of Oncology (2020) 31(7) 569-581

Pembrolizumab plus Neoadjuvant Chemotherapy Improves Pathologic Complete Response Rates in Triple-Negative Breast Cancer Schmid P, Cortes L, Pusztai L Journal of Clinical Outcomes Management (2020) 27(7) 53-55

TROPiCS-02: A Phase III study investigating sacituzumab govitecan in the treatment of HR+/HER2-metastatic breast cancer Rugo HS, Bardia A, Tolaney SM et al. Future Oncology (2020) 16(7) 705-712

Enhancing global access to cancer medicines Cortes J, Perez-García JM, Llombart-Cussac A et al. CA Cancer Journal for Clinicians (2020) 70(7) 105-124

Team

Group Leaders in the Centre
Dr Ranjit Manchanda, Professor Thomas Powles

Postdoctoral Researchers
Dr Alice Shia, Dr Graeme Thorn

PhD Students
Ms Juliette Chupin, Ms Farah Louise Lim

Biography

Profile

• Professor of Experimental Cancer Medicine and Honorary Consultant in Medical Oncology, St Bartholomew's Hospital & Barts Cancer Institute, November 2013-present
• Foundation Professor of Cancer Medicine and Honorary Consultant in Medical Oncology, BSUH NHS Trust, BSMS, 2010-2013
• Clinical Director, Clinical Investigation and Research Unit, BSUH NHS Trust, BSMS, 2010-2013
• Senior Clinical Lecturer and Consultant in Medical Oncology, Director Hammersmith Early Clinical Trials Unit, Imperial College London, 2005-2010
• Research Lead, Breast Cancer & Phase 1 Programme, Charité University Hospital, Berlin, Germany, 2002-2005
• Lead Oncologist for Breast Cancer Services at Multidisciplinary Breast Centre, Charité University Hospital, Berlin, Germany, 2001-2005
• Director, Clinical Trials Unit, Department of Oncology & Haematology, Charité University Hospital, Berlin, Germany, 2000-2005