In a rare and significant milestone for an Australian-discovered therapy, Pfizer Inc has commenced a Phase 3 clinical trial to study a potential new medicine for advanced breast cancer, based on pioneering research from Monash University and the Cancer Therapeutics Cooperative Research Centre (CTx).
The first-in-class therapy is being studied as a treatment in adults with HR+, HER2- advanced or metastatic breast cancer whose disease progressed following prior treatments.
The potential medicine, referred to as 'PF-07248144' and co-invented by scientists from the Monash Institute of Pharmaceutical Sciences (MIPS), blocks two proteins – KAT6A and KAT6B – which help control how genes are switched on and off. Because these proteins influence how cells grow and develop, finding ways to block them can 'turn down the volume' on those genes and slow the cancer's ability to grow and spread.
The advancement to Phase 3 clinical trials is supported by highly encouraging Phase 1 results, where PF-07248144, in combination with fulvestrant (a type of hormone therapy), achieved a 37 per cent objective response rate in patients.
The KAT6 platform was licensed to Pfizer through the CTx' commercialisation partner Oncology One in 2018, and Pfizer progressed the program to ultimately deliver PF-07248144. From MIPS, the project was co-led by medicinal chemists, Professor Paul Stupple and Dr Ylva Bozikis.
Professor Stupple said it's exciting to see PF-07248144 in Phase 3 clinical trials and a step closer to patients. "The discovery of "PF-07248144 is an important scientific advance. For the first time, selective targeting of KAT6 opens new avenues for the treatment of advanced breast cancers."
"This program represents what can be achieved through scientific collaboration and uniting diverse expertise. By bringing together skills and knowledge across academia and industry we were able to translate early stage research into a promising new therapy now advancing in clinical trials. Seeing this work benefit patients and progress to Phase 3 trials is a wonderful testament to the impact of true collaboration."
Professor Susan Charman who has also played a critical role in the development of the KAT6 inhibitors through the Centre for Drug Candidate Optimisation, MIPS, said the candidate "represents a marked improvement in potency, selectivity, and drug-like properties."
While treatment options have improved, patients with HR+, HER2- advanced breast cancer continue to face significant challenges from therapy resistance and disease progression.
Professor Brendon Monahan, former Chief Scientific Officer for the CRC and now based at MIPS, added "Pfizer's Phase 1 study provided a strong clinical proof of concept that targeting KAT6 offers a novel epigenetic approach for treating patients with breast cancer. The direct advancement to Phase 3 trials underscores the significance of this work and highlights the quality of the contribution from MIPS and the wider CTx group in discovering this first-in-class therapy."
Cancer Therapeutics CRC evolved into Canthera Discovery in 2021. Managing Director, Dr Alan Robertson said, "This is a major milestone, and we thank Pfizer for their tireless efforts in advancing the program. Our goal has always been to find new cancer treatment options for patients, and with this announcement, we are one step closer to fulfilling that vision."
This program was a multidisciplinary and collaborative effort including Australian researchers from MIPS, WEHI, Peter MacCallum Cancer Centre, CSIRO, Griffith University, St Vincent's Institute of Medical Research, and Children's Cancer Institute.
