KTRA: VAL-083 Poster Updates
NASDAQ:KTRA
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Kintara Therapeutics Inc. (NASDAQ: KTRA) provided an update to their VAL-083 ongoing newly-diagnosed, recurrent and first line glioblastoma (GBM) Phase II trials in two posters presented at the Society of Neuro-Oncology (SNO) annual meeting on November 20. The trials are enrolling MGMT-unmethylated (1) glioblastoma (GBM) patients in the recurrent and newly diagnosed adjuvant and newly diagnosed first line settings. The larger trial at MD Anderson in Texas is evaluating 77 patients in the recurrent group and 27 in the newly-diagnosed, adjuvant group. The second trial is being conducted in China at the Sun Yat-sen University Cancer Center and is evaluating 29 newly diagnosed first line patients. Results from these studies have helped guide the design of the upcoming Global Coalition for Adaptive Research (GCAR) AGILE study which is expected to enroll Kintara patients before year end.
We provide an update to the two active Phase II trials and a review of the posters recently presented. Newly diagnosed patients in the adjuvant setting at the MD Anderson trial achieved 10.0 months of median progression free survival (mPFS) compared to a historical range of 5.3 to 6.9 months. Recurrent patients in the other arm of this same trial reached 8.5 months of median overall survival (mOS), which compares to previous observations of 7.2 months. The Sun Yat-sen trial achieved 8.7 months of mPFS for newly diagnosed first line patients which also compares to historical benchmarks of 5.3 and 6.9 months.
The posters provide updated interim analysis on the trial being conducted at MD Anderson in Texas and in China at Sun Yat-sen University.
‣ Phase 2 clinical trial of VAL-083 in newly diagnosed MGMT-unmethylated GBM
◦ The “MD Anderson” study
‣ Phase 2 Study of VAL-083 in MGMT-unmethylated GBM in the recurrent and adjuvant setting
◦ The “Sun Yat-sen” study
MD Anderson
The first poster presented results from the MD Anderson study with data updated as of October 23, 2020. The trial enrolled 84 subjects into the recurrent arm (Group 1) and 30 subjects into the adjuvant arm (Group 2). Group 1 is split between the 40 mg/m2/d and 30 mg/m2/d dosing groups. The dose was reduced to address the higher potential for myelosuppression and increase the number of VAL-083 cycles a patient may receive.
Interim results for the Group 1 MD Anderson study are mOS of 7.6 months, with the 40 mg cohort at 6.5 months and the 30 mg cohort at 8.5 months. Results for Group 1 are placed into context with recurrent historical results for lomustine with an mOS of 7.2 months.
Interim results for Group 2 was mPFS of 10.0 months and mOS of 16.5 months. Group 2 results are relative to use of temozolomide with mPFS of 6.9 months. The design of the Group 2 study is the structure that will be used in the upcoming GCAR trial.
Exhibit I – MD Anderson Evaluable Subjects, Newly-Diagnosed, Adjuvant (2)
Assessment of the MD Anderson trials supports a 30 mg/m2/d dose as the optimal balance between safety and disease control. VAL-083 at this dose is well tolerated in the unmethylated GBM population and may provide greater mOS than temozolomide.
Sun Yat-sen
The Sun Yat-sen study, with data updated as of October 21, 2020, has enrolled a total of 29 newly diagnosed patients that receive VAL-083 after surgery. Median progression free survival for all patients was 9.3 months, and mPFS for the 30 mg/m2/d of 8.7 months (3). Median overall survival was 19.6 months for all dosage groups and 18.2 months for the 30 mg/m2/d group.
Exhibit II – Sun Yat-sen Survival (4)
The Sun Yat-sen study poster concluded that VAL-083 at 30 mg/m2/d in combination with radiation is generally safe and well tolerated with multiple treatment cycles successfully completed in the adjuvant setting. Compared to historical studies using temozolomide, VAL-082 was able to improve PFS and OS in the same setting.
Global Coalition for Adaptive Research (GCAR) Study
The Global Coalition for Adaptive Research (GCAR) study, which we have discussed in our initiation has introduced another sponsor to its roster. The Australian company Kazia Therapeutics (NASDAQ: KZIA) was added to the GBM AGILE pivotal study with the drug paxalisib, a small molecule inhibitor of the PI3K/AKT/mTOR pathway. Kazia expects to enroll first patients in 1Q:21 and recently presented a poster at SNO which reported median progression free survival of 8.4 months and median overall survival of 17.5 months. Kazia joins Bayer (XTERA: BAYN.DE) and its GBM candidate regorafenib.
Kintara announced that it had been selected to participate in the GCAR GBM AGILE pivotal study in a June 4, 2020 release. GCAR is an international partnership including some of the world's leading clinical, translational, and basic science investigators. The group is working on development projects in GBM to advance effective therapies in promising biomarker defined populations. GBM AGILE is uniquely designed as a long-standing platform which will evaluate multiple investigational therapies for newly diagnosed or recurrent GBM to determine if new treatments are an improvement over standard of care. Unlike traditional trials that evaluate one therapy at a time, GBM AGILE will test several therapies or treatment arms simultaneously. One of the key benefits of the structure is a shared control arm that has already started enrolling. Not only will this reduce the number of additional subjects needed when Kintara begins enrolling, it will also allow them to share the cost of the arm with other participants. Another important benefit of the structure is that new treatment arms can be quickly added and evaluated at any time, while under-performing approaches can be dropped. GCAR selected GBM as a target indication due to the high death rate and lack of other effective therapies. The trial design is a seamless Phase II (Efficacy and Safety) / Phase III (Confirmatory) trial that can provide pivotal data for approval.
Participation in the program is a huge win for Kintara as it includes industry-recognized luminaries in the GBM oncology space. The FDA has cleared the trial design and has provided a letter of support to GCAR and trial sites are already enrolling. This saves months of time, effort and cost for Kintara and provides an independent affirmation of VAL-083. The adaptive trial design is another plus that can expand the target population appropriate for VAL-083.
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1. MGMT: O(6)-methylguanine-DNA methyltransferase
2. O’Brien, B. et al. Phase 2 study of dianhydrogalactitol (VAL-083) in patients with MGMT unmethylated, bevacizumab naïve glioblastoma in the recurrent and adjuvant setting. Poster Presentation 25th Annual Scientific Meeting of the Society for Neuro-Oncology (SNO). November 2020.
3. The 30 mg/m2/d dose will be exclusively used in the registrational GCAR trial.
4. Chen, Z. et al. Phase 2 Clinical Trial of VAL-083 in Newly Diagnosed MGMT-unmethylated GBM. Poster Presentation 25th Annual Scientific Meeting of the Society for Neuro-Oncology (SNO). November 2020.
