On April 7, 2020 Kazia Therapeutics Limited (ASX: KZA;NASDAQ: KZIA), an Australian oncology-focused biotechnology company, reported to share positive interim data from its ongoing phase II study of paxalisib (formerly GDC-0084) in glioblastoma, the most common and most aggressive form of primary brain cancer (Press release, Kazia Therapeutics, APR 7, 2020, View Source [SID1234556187]).
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Key Points
Interim analysis of Part A (escalation cohort) (n=9) showed median overall survival (OS) of 17.7 months, representing a clinically meaningful extension of life when compared to the 12.7 months associated with the existing standard of care, temozolomide
Interim analysis of all evaluable patients (Part A = 9; Part B = 21) shows median progression-free survival (PFS) of 8.5 months, broadly in line with previous analysis, and comparing favourably to the 5.3 months associated with temozolomide
The longest-treated patient remains progression-free 19 months after diagnosis
Approximately half the enrolled patients remain on drug and both OS and PFS figures may further improve as the trial progresses toward conclusion
Kazia expects to present further data in 2H CY2020 and final data in 1H CY2021
Summary of Paxalisib Data in Comparison to Temozolomide (existing standard of care)
Temozolomide
(FDA-approved treatment)
Paxalisib
(interim phase II data)
Progression-Free Survival (PFS)
Measures ability of a drug to slow
growth of a tumour
5.3 months
8.5 months
Overall Survival (OS)
Measures ability of a drug to
prolong life
12.7 months
17.7 months
Kazia CEO, Dr James Garner, commented, "This is an excellent result, and we are delighted with the emerging data. The ‘gold standard’ for any new cancer treatment is the ability to extend life – an especially challenging goal in a disease such as glioblastoma – and this data provides our first evidence that paxalisib may achieve this objective in a very challenging patient population."
He continued, "There have not been any new drug treatments for newly-diagnosed glioblastoma patients for over twenty years, and we aspire to change that situation. We believe that paxalisib is rapidly becoming one of the most promising drug candidates in the global pipeline for this very challenging disease and we will be working strenuously to make it available to patients as quickly and efficiently as possible. The study continues to follow a number of patients who remain on treatment, and we currently expect to report a further data read-out in the second half of the year."
Background
The reported overall survival (OS) figure of 17.7 months represents a strong signal of clinical efficacy. The existing, FDA-approved standard of care, temozolomide, is associated with an OS of 12.7 months in this patient population[1]. Comparison between different studies is always imprecise, but the magnitude of the numerical difference provides powerful evidence that treatment with paxalisib may extend life in this patient group.
The reported progression-free survival (PFS) figure of 8.5 months is slightly better than the figure of 8.4 months previously reported in November 2019. Temozolomide is associated with a PFS of 5.3 months in this patient population.
Before losing patent protection, temozolomide achieved peak sales in excess of US$ 1 billion per annum, which provides an indication of the commercial opportunity associated with a new treatment for glioblastoma.
Thirty patients were enrolled to this study, comprising 9 in Part A, and 21 in Part B. Data reported here are provisional figures from Part A (for OS) and from the entire study population (for PFS), but may change as ongoing patients proceed through the study. The study has been conducted at leading centers of excellence in the United States.
The safety of paxalisib remained broadly consistent with prior experience, with hyperglycaemia (raised blood sugar), oral mucositis (mouth ulcers), and low-grade rash among the most common drug-related toxicities.
In addition to this phase II study in glioblastoma, four other studies are underway with paxalisib in different forms of brain cancer, and it is anticipated that several of these will provide initial efficacy data during CY 2020.
This data had been accepted for presentation at the annual meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) in San Diego, CA from 24 -29 April 2020. However, given the cancellation of the AACR (Free AACR Whitepaper) meeting due to the COVID-19 outbreak, Kazia has determined to provide an update to investors via this ASX announcement.
Next Steps
The phase II study remains ongoing, with approximately half of the total enrolled patient population still receiving drug at the time of analysis and a number of additional patients still in follow-up. At this stage, Kazia expects to present further data in 2H CY2020, and final data in 1H CY2021.