VAL-083 Phase II Topline Data (MD Anderson) – Adjuvant Arm
Kintara Therapeutics, Inc. (NASDAQ:KTRA) announced topline results from its Phase II study of lead candidate, VAL-083, as adjuvant therapy in newly-diagnosed glioblastoma multiforme (GBM) patients. The last patient in this group was dosed on June 3rd and the topline announcement is an update from the previous results that were presented in a poster at the American Association for Cancer Research annual meeting in April 2021.
Adjuvant therapy, also known as adjunct therapy, is therapy that is given in addition to primary/initial therapy to increase efficacy; VAL-083 was given as an adjuvant for temozolomide (chemotherapy). The study is an open-label, Phase II study being conducted at MD Anderson Cancer Center in Houston, TX. The trial has two arms enrolling patients with unmethylated O6-methylguanine–DNA methyltransferase (MGMT) promoter (chemotherapy resistant). Topline results from the recurrent arm were announced in July.
The newly-diagnosed adjuvant arm enrolled 39 patients, with 36 evaluable, initially receiving a dose of 30 mg/m2/day on days 1, 2, and 3 of a 21-day cycle. The prior update, which was provided in an April 10 poster and measured results as of March 12, 2021 found median progression free survival (PFS) of 10.0 months and median overall survival (mOS) of 16.5 months. This included 33 patients. In the most recent update, PFS and mOS remained the same but with an increase in evaluable subjects to 36 and a cutoff date of September 13, 2021.
PFS was 10 months, with a confidence interval ranging from 8.2-10.8 months, comparing favorably with historical data in the 5.3-6.9-month range. mOS was 16.5 months, with confidence interval of 13.3-19.3 months, comparing favorably to historical ranges of 12.7-16.0 months. Myelosuppression was the most common adverse event. One patient experienced a serious adverse event that was possibly treatment related.
VAL-083 Phase II Topline Data (MD Anderson) – Recurrent Arm
Kintara provided topline data from the recurrent arm of its MD Anderson Phase II clinical trial in a July 1 press release. Median overall survival (mOS) for the 48 efficacy-evaluable patients at the 30 mg/m2/day dose level was 8.0 months with a 95% confidence interval of 5.9 to 9.9 months. This is a slight increase from the value provided at the prior update of 7.9 months reported in November 2020. The data demonstrate better survival than the adverse side-effect prone lomustine, which has shown a mOS of 7.2 months.2 For all patients in the trial, including the no longer applied 40 mg/m2/day dosing, mOS was 7.5 months, matching the number reported last November.
MD Anderson Trials
Kintara’s MD Anderson trial is a Phase II, open-label, two-arm, biomarker-driven study evaluating VAL-083 in MGMT unmethylated GBM patients, known to be resistant against current standard-of-care chemotherapy. Efficacy endpoints include OS and PFS. The recurrent arm of the study is evaluating glioblastoma multiforme (GBM) patients who have been pre-treated with temozolomide (TMZ). The study was designed to enroll up to 83 patients in total. On April 12, 2021, Kintara provided another update for the trial in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting. The trial enrolled 89 patients into the recurrent arm, with 35 and 54 patients receiving 40 mg/m2/d and 30 mg/m2/d dosing, respectively. At that time, mOS for all 83 evaluable patients who had completed at least one cycle of treatment was 7.5 months. For the 48 evaluable patients initially receiving the 30 mg dose, mOS was last reported at 7.9 months (now at 8.0 months).
GCAR AGILE Trial
In January 2021, Kintara announced the start of patient recruitment in the Global Coalition for Adaptive Research (GCAR) registrational Phase II/III clinical trial for glioblastoma multiforme (GBM). Kintara’s candidate, VAL-083, will be considered in three subpopulations: newly-diagnosed methylated O6-methylguanine-DNA methyltransferase (MGMT) GBM, newly-diagnosed unmethylated MGMT GBM and recurrent GBM.
In the January press release, Kintara announced that GCAR would be adding an additional active arm to VAL-083’s study in newly-diagnosed methylated GBM patients, complementing the existing arms investigating newly-diagnosed unmethylated and recurrent GBM. Methylated GBM patients see some benefit from the current standard-of-care temozolomide (TMZ) and may be better served by VAL-083.
As of May 18th, 2021 GCAR has screened over 600 patients for the AGILE trial. Based on conversations held between Kintara management and GCAR, it is estimated that the first stage of the adaptive trial will graduate into the second stage in 2H:22.
On August 17, Kintara provided an update that 26 US sites had been activated in the GCAR trial as of August 16, 2021. It is expected that 39 sites will be active by year end. Since January, GCAR has accelerated the pace of clinical site activation. GCAR is targeting 150-200 patient enrollment in the Kintara arm of the study at over 40 sites in the US and Canada, with potential of 65 clinical trial centers worldwide.
In the latest update regarding the adjuvant arm of the trial, PFS was 10 months, with a confidence interval ranging from 8.2-10.8 months, comparing favorably with historical data in the 5.3-6.9-month range and mOS was 16.5 months, with confidence interval of 13.3-19.3 months, comparing favorably to historical ranges of 12.7-16.0 months. PFS and mOS match results from the previous update in April. The most common side effect was myelosuppression, and one patient experienced a severe adverse event that may have been treatment-related. Kintara’s VAL-083 candidate is poised to make a material impact in treatment resistant GBM patients, a population that represents more than half of the total GBM population. VAL-083 may also acquire market share in the MGMT-methylated population as well, although its efficacy in this subpopulation is only now being evaluated in the GCAR AGILE trial. Kintara offers exposure to two large oncology markets and is developing two assets primed to enter pivotal studies. With a wealth of data available for VAL-083 and an unmet need in CMBC, we see Kintara as diversified and undervalued.
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1. Compiled by Zacks Analyst
2. Wick, W et al (2017) N.Eng.J.Med . 377:1954 1963 ; 6 . NCCN guidelines (CNS cancers, 2017); 7. Tanguturi SK, et al. NeuroOncol.19(7):908 917 (2017). EORTC 26101, for patients with recurrent MGMT unmethylated GBM treated with lomustine alone.
3. Source: Kintara Corporate Presentation August 2021