A promising combination therapy that offers a new approach to targeting a highly aggressive and treatment-resistant type of breast cancer, has advanced to clinical trial for the first time. This novel treatment could offer hope for patients who have few options to treat the deadly disease.
The world-first clinical trial is recruiting 24 women with metastatic triple-negative breast cancer, who will receive the combination therapy at sites in Queensland.
It stems from pivotal research led by QIMR Berghofer scientists in collaboration with Australian drug development company Kazia Therapeutics, which combined its drug candidate, paxalisib, with immunotherapy in pre-clinical models.
The team discovered that this combination approach triggers a molecular epigenetic process where dormant cancer cells are re-programmed, making them visible to the immune system, while also reinvigorating the immune cells to fight the tumour cells.
Triple-negative breast cancer is more commonly diagnosed in younger women, aged under 40 years. If the disease has spread to other parts of the body, treatment options are very limited, with immunotherapy and other standard treatments only effective for a small subset of patients. There is an urgent need for new treatment options.
QIMR Berghofer’s Professor Sudha Rao said the hope is to prolong survival of patients through the new combined therapy, which targets the dormant cancer cells that drive the spread and recurrence of the disease, and rejuvenates the immune system to more effectively fight the cancer.
“There is no cure for advanced triple-negative breast cancer and the life expectancy for these women is tragically short. We want to identify treatments to extend the duration and quality of life of these patients,”
“Immunotherapy works by activating the patients’ own immune system to fight off cancer. Our pre-clinical research has shown for the first time that paxalisib activates dormant cancer cells, making them visible to the immune system and helping immunotherapy to effectively function.
“This could be a game changer because we know immunotherapy is only successful in a handful of patients with metastatic triple-negative breast cancer. Our pre-clinical findings have given us real hope that paxalisib could ensure immunotherapy is effective for more patients,” Professor Rao said.
Paxalisib, which was designed to treat brain cancers, has the unique quality of being able to cross the blood-brain barrier. This is significant for metastatic triple-negative breast cancer because the brain is one of the common sites the cancer spreads to when disease progresses.
Known as the “Advanced Breast Cancer – paxalisib” study (ABC-Pax), it is the first clinical trial to assess the safety and efficacy of paxalisib in combination with pembrolizumab (KEYTRUDA®) or olaparib (LYNPARZA®) in women with triple-negative or BRCA mutation-associated metastatic breast cancer.
The multi-centre, open-label phase 1b study is being sponsored by Kazia Therapeutics, and will enrol 24 patients from leading cancer treatment centres in Queensland, including the Royal Brisbane and Women’s Hospital, with participants receiving the combination therapy for up to 12 months.
"The novelty of the science that Professor Rao has proposed with this dual combination of paxalisib and immunotherapy could advance the treatment of women with aggressive breast cancer, and we are excited to support this unique clinical study,” Dr John Friend, CEO Kazia Therapeutics said.
“These new pre-clinical data were presented at the San Antonio Breast Cancer Symposium on December 12, 2024, and highlight the potential therapeutic synergies between paxalisib and the checkpoint inhibitor, pembrolizumab (KEYTRUDA®) as well as paxalisib and the PARP inhibitor, olaparib (LYNPARZA®), when used in combination in a pre-clinical model of immunotherapy-resistant triple-negative breast cancer,” he said.
In another world-first, the ABC-Pax clinical trial will also test a ground-breaking, non-invasive liquid biopsy digital pathology platform developed by Professor Rao and her team, which aims to monitor the behaviour of cancer cells and immune cells in real time.
“By regularly analysing blood samples from trial participants using our liquid biopsy digital pathology platform, we will be able to track the effectiveness of the treatment. This approach represents a major advance in precision medicine by offering a faster and more accurate way to monitor patient progress,” Professor Rao said.
“We hope this liquid biopsy test could one day become a standard tool for detecting the spread of cancer early, when treatment could be most effective.”
Professor Rao said she is grateful for the generous support she has received to advance the test, including from the Daniela Dwyer Foundation, Breast Friends, and the family and friends of Canberra mother-of-two Melanie Swan.
“This support is vital to help us advance our work. In particular, my team and I are inspired every day by two very special women who championed our research – my friend Melanie Swan who passed away from metastatic breast cancer when she was 43 years old, and Daniela Dwyer who was 34 years old when she passed away from brain cancer. Daniela’s blood samples, which she provided after receiving paxalisib on compassionate grounds, have been pivotal to helping us advance our research,” Professor Rao said.
About the clinical trial:
- Interested participants are asked to discuss this trial and the specific eligibility criteria with their oncologist.
- The clinical trial has begun recruiting patients at the Royal Brisbane and Women’s Hospital, with more trial sites planned for the Sunshine Coast and Gold Coast in Queensland.