and Education (CAHRE) Cabrini Monash University Department of

Cabrini Monash University Department of Medical Oncology – The Szalmuk Family Department of Medical Oncology

Head: Professor Gary Richardson OAM

The department undertakes a wide range of research activities, largely building upon the second largest clinical service in Victoria (the largest private service in Australia). Activities include new drug trials, translational research in breast, colorectal and ovarian cancers, medical informatics and patient-reported outcome measures.

Head of Department Professor Gary Richardson OAM (Phase I trials, Gynaecologic Cancers, Lung Cancer)

Principal Investigators Dr Yoland Antill (Breast Cancer) Associate Professor Ben Brady (Melanoma, Lung Cancer) Dr Anis Hamid (Phase I trials) Dr Andrew Haydon (Gastrointestinal Cancers, Melanoma) Associate Professor Melita Kenealy (Haematologic Malignancies) Associate Professor Lara Lipton (Gastrointestinal Cancers) Dr David Pook (Genitourinary Cancers) Associate Professor Jeremy Shapiro (Gastrointestinal Cancers, Genitourinary Cancers)

Associate Investigators Dr Michael Dickinson Dr Lucy Gately Associate Professor Ian Haines Dr Despina Handolias Dr Henry Januszewicz Dr Sem Liew Dr Esther Lin Dr Ben Markman Professor Miles Prince Dr Gaurav Srivastava Dr Robert Stanley Dr Mark Voskoboynik Dr Michelle White Associate Professor Max Wolff Dr Kirsten Herbert Dr Dan Tran Dr Emma Beardsley Dr Samantha Dean Dr Peter Lau Dr Jo Ann Chow

Senior Research Fellow Dr Tali Lang

Research Coordinators Li Hoon Lai (Team Leader) Demis Balamatsias Lyanne Cottee Theresa Ealdama Kate Hurford Simona Infantino Simer Khaira Leyna Tran Rochelle Woods

CTA Ethics Specialist Dr Luz Yévenes

Family Cancer Clinic Lynne McKaye, Genetic Counsellor Brightways Breast Cancer Program Dr Joanna Morgan, Specialist Breast, Thyroid and Parathyroid Surgeon Dr Karen Taylor, Radiation Oncologoist Melissa Vereker, Data Manager and MDT Meeting Coordinator

Acknowledgement of Research Coordinator Staff who have left (2019-2020) Daphne Antonopoulos, Research Coordinator Stephanie Groube, Associate Genetic Counsellor Jacqui Hastings, Acting Brightways Coordinator Anna Uhe, Clinical Trials Assistant

The program provides significant benefits for patients, including access to treatments not yet in the marketplace, close monitoring and testing, and collection of valuable information that can help others. The department is seen as a partner of choice by the pharmaceutical and biotech industries, particularly in the area of precision medicine. We have a highly trained dedicated team that provide the highest level of care for all patients participating in clinical trials. Development and maintenance of a robust research program not only benefits patients in terms of access to new active anti-cancer agents. It also allows us to attract the best and brightest researchers and clinicians, who improve the consumer experience even more.

Highlights

Cancer Institute Phase I Cabrini secured a $6m grant to begin development of a Cancer Institute. Phase I involves establishment of an interim “Cancer Institute” in the old Day Oncology Unit at Malvern incorporating a Cancer Trials Unit, Trials Pharmacy, Exercise Research (gymnasium and exercise laboratory) and Wellbeing (dietetics, psycho-oncology and pastoral care). The express purpose of phase I is doubling patient numbers on clinical trials and commencing formalised research into exercise and wellbeing in cancer patients. It is anticipated this will be completed by the end of 2020.

Auric Grant The successful grant application will allow development of an innovative project to create a new research stream at Cabrini to investigate novel approaches to improve the outcomes for cancer patients. It will assess the potential positive benefits of exercise and exercise therapy/rehabilitation in patients with cancer, by systematic, sequential, objective physiologic measurements of patients during and after cancer treatment. It is an ambitious project, as there are very few exercise laboratories in the world dedicated to cancer patients. The only other facility like this in Australia is at the Edith Cowan University, and it has a more general exercise laboratory centred on cardiovascular research. The only comparable program is at Memorial Sloan Kettering in New York, one of the world’s leading cancer centres, which concentrates study on the utility of different methods to characterise the chronic and long-term adverse cardiovascular side-effects of conventional and novel cancer therapies. The grant will create a facility that allows original research to break new ground in cancer management.

Phase I Trial Program The Phase I Oncology Clinical Trials program at Cabrini Health addresses a key clinical need in the longitudinal care of cancer patients in the service. Specifically, the program is designed to offer patients with advanced and refractory cancer the opportunity to access therapeutics in development with the primary aim of trialling potentially effective therapy in the context of a clinical trial. The nature of phase I trials is collaborative, involving multiple clinical disciplines, providers and industry sponsors in both research and patient-directed activities. The suite of phase I studies comprise either novel immunotherapy drugs or targeted therapies designed to attack a particular growth regulatory pathway in cancer cells. We have recruited Dr Anis Hamid, who was previously working at the highly esteemed DanaFarber Cancer Institute in Boston, USA, to develop and run the program. He has opened trials for both unselected tumour types and in selected tumour types. The program is highly successful and offers our patients treatments that would normally not be available for years.

Our Research

Phase I Trial Program A phase I study of APL-501, an anti-PD-1 antibody, in patients with recurrent or advanced solid tumours. APL-501 is a humanised monoclonal antibody targeting programmed cell death-1 (PD-1). It was evaluated in patients with advanced recurrent and relapsed solid tumors who had not been previously treated with an immune checkpoint inhibitor. Twenty-two patients were enrolled with a mean age of 62.1 (SD: 12.2) years. No dose limiting toxicities were reported. Fifteen patients (68.2%) had related AEs; two patients (9.1%) had Grade ≥ 3 related AEs to APL-501. Eight patients had stable disease and two patients had partial response by RECIST (esophageal adenocarcinoma and cancer of unknown primary). Seven patients remained on therapy for ≥ 24 weeks. The recommended phase 2 dose (RP2D) has been determined to be 400 mg IV every 14 days (non-weight-based) based on safety and PK modeling. Preliminary results indicate clinical activity of APL-501 in relapsed/refractory malignant disease with a generally tolerable safety profile. Clinical trial information: NCT03053466.

Immunotherapy Program Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: EORTC 1325-MG/Keynote 054 double-blinded phase 3 trial. Phase 3 double-blind trial to evaluate pembrolizumab vs placebo in patients with resected high-risk stage III melanoma. A total of 1019 patients were randomised to pembrolizumab at a flat dose of 200 mg (N=514) or placebo (N=505) every three weeks for a total of 18 doses or until disease recurrence or unacceptable toxicity. In the overall population, the three-year cumulative incidence of distant metastasis being the first recurrence was 22.3% (pembrolizumab group) vs 37.3% (placebo group) (HR 0.55, 95% CI 0.44-0.69). Relapse-free survival was increased in all patient subgroups, including stage, Braf-V600E/K mutation status, and PD-L1 score. Clinical trial information: NCT02362594

Medical Informatics: Database Evaluation Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2+/HR+ metastatic breast cancer: TABITHA Database Analysis. Endocrine therapy is the backbone of treatment in hormone receptor positive (HR+) disease, but the role of the addition of endocrine therapy following chemotherapy in HER2+/HR+ disease remains unclear as pivotal first line clinical trials excluded endocrine therapy use. Data from a multi-site community cohort of consecutive HER2+ metastatic breast cancer patients diagnosed between 1 January 2012 and 31 August 2019 was examined. Of 132 eligible patients included in the analysis, 78 (59.1%) received endocrine therapy and 54 (40.9%) did not. Median follow up was 25.9 months. The addition of endocrine therapy was associated with improved progression free (HR 2.1, 95% CI 1.2-3.5, p = 0.007) and overall survival (HR 2.7, 95% CI 1.2-5.5, p = 0.007) in multivariate analysis.

Dr Anis Hamid

PRINCIPAL INVESTIGATOR (PHASE I TRIALS)

Dr Anis Hamid has found great pleasure in joining the Cabrini Institute as a medical oncologist with a specific interest in the development and conduct of early phase cancer trials. Anis studied medicine at the University of Melbourne and completed clinical training at tertiary academic centres around Melbourne including Cabrini, culminating in a Clinical Trial Fellowship at the Olivia Newton-John Cancer Wellness and Research Centre focusing on early drug development, phase I and genitourinary cancer trials. He then worked at Dana-Farber Cancer Institute in Boston, Massachusetts as a translational researcher and PhD student with a focus on prostate cancer genomics, computational oncology and precision cancer medicine, ongoing between Boston and the University of Melbourne.

Phase I trial program growth Anis returned to the Cabrini Institute to help spearhead the phase I trial program with Professor Gary Richardson OAM, a distinct privilege which enables him to translate his research interests to outstanding care for patients in the Cabrini community.

The Cabrini Institute has grown an exceptional clinical trial program exemplified by diverse and novel studies in the phase I portfolio. Phase I or ‘early phase’ clinical trials are centered around offering patients the opportunity to participate in studies of novel drugs-in-development. Our mission is critical in the cancer journey of many patients with a diagnosis of advanced care. Enrolment in phase I trials often allows patients to trial a promising class of treatment, such as immunotherapy, that may be otherwise unavailable due to a lack of mature evidence from later phase studies. Over the last six months, the phase I program has grown considerably as we assess and offer more patients the option of enrolment on up to six to ten trials at any one time. Teamwork has been crucial in the growth of the program, with medical investigators working closely with study coordinators, nursing staff, pharmacists, research associates and industry sponsors to deliver the exemplary level of care we expect for our patients at Cabrini. A growing team requires outstanding communication and commitment; indeed this is a cornerstone value of the Cabrini Institute as a center of excellence in clinical trial research.

Future focus The future holds exciting opportunities to expand the diversity of early phase trials at Cabrini to ultimately provide more opportunity and choice for patients. We are actively pursuing trials of novel treatments: ‘pathway-directed’ therapies, immunotherapies and those that target specific genetic features of an individual patient’s cancer. In this sense, we are excited to build precision genomic therapies and tumour sequencing as a special area of focus. We have recently launched a multi-disciplinary molecular tumour board, chaired by Professor Gary Richardson OAM, to engage colleagues and partner institutions in this area. It is key that efforts to expand clinical trials and associated research are ultimately tied back to the needs of our patients. As a new Cancer Institute is realised at Cabrini in the coming years, the role developing effective cancer therapies and launching early phase clinical trials remains ever crucial in the mission of providing forwardlooking and holistic patient care.