Kazia Therapeutics Ltd’s (ASX:KZA) (NASDAQ:KZIA) promising GDC-0084 drug is joining the pivotal GBM AGILE trial, an international, academic-led, multi-drug adaptive phase II / III study in glioblastoma.
GDC-0084, a small molecule inhibitor of the PI3K/AKT/mTOR pathway, is being developed to treat glioblastoma, the most common and aggressive form of primary brain cancer in adults.
It is expected that data from GBM AGILE will be used to seek marketing approval for GDC-0084 from FDA and other regulatory agencies.
Edison Investment Research Limited has maintained its indicative value of US$93 million for Kazia (US$12.9 per ADR; current price US$4.35 per ADR).
Following is an extract from Edison’s research report on Kazia:
AGILE: A new approach to a potentially pivotal study
The Glioblastoma (GBM) Adaptive Global Innovative Learning Environment (GBM AGILE, NCT03970447) trial is an adaptive Phase II/III platform designed to evaluate multiple therapies against one rolling control group; it currently has 11 US centers and plans to add leading international centers to its network. It is a clinician-led trial with an FDA-agreed single Master Clinical Trial Application. On entering the study, the newly diagnosed GBM AGILE patients undergo surgery to remove the tumor followed by radiation therapy combined with temozolomide (TMZ) (Stupp regimen). The difference tested is overall survival in the randomized maintenance phase using either TMZ or GDC-0084.
AGILE uses a stage 1, which recruits up to 150 patients to assess efficacy compared against patients with a similar profile in the control arm. If this stage appears positive, up to 50 patients might be recruited to a stage 2 expansion cohort for confirmatory data. Currently, the kinase inhibitor regorafenib (Stivarga, Bayer), approved for advanced gastrointestinal cancers but not GBM, is being tested. AGILE has several advantages: a faster start, an existing design and an expanding infrastructure plus involvement of key opinion leaders, a big benefit in the event of positive data, regulatory review and launch. However, Kazia will not have direct control over the study, so any problems or delays might take longer to resolve.
Kazia presented a poster in 2019 on the Phase IIa (NCT03522298) GDC-0084 dose-ranging results showing median progression-free survival (PFS) of 8.4 months in TMZ-resistant patients. Published studies indicate comparison PFS values of 5.9 months. Kazia is recruiting a 20-patient expansion cohort and further data should be available during 2020; this will help to inform AGILE expectations.
Cantrixil efficacy indications expected in 2020
Cantrixil is in a small Phase I study, with results expected by management in H120. Cantrixil could become a standard treatment for third-line ovarian cancer patients who now have few therapy alternatives. Interim data were presented in September.
Valuation: Indicative value of $93m
Kazia is aiming for a 2024 GDC-0084 US launch. It had $3.7m cash at 30 June 2019, boosted in H120 by a $2.6m net placing and the expected cash $1.0m tax credit in December. We maintain our indicative value of $93m ($12.9/share). We have assumed that Cantrixil will be partnered If the current trial data is strong.