CTNI-32 - Phase 2 Study of VAL-083 and Radiotherapy in Newly Diagnosed MGMT-unmethylated GBM

Friday, November 18, 2022

7:30 PM – 9:30 PM ET

Location: West/Central Hall

Author(s)

Jeffrey Bacha, BSc., MBA

Edison Oncology Holding Corp
Menlo Park, United States
SK

Sarath Kanekal

Kintara Therapeutics
Menlo Park, United States
CK

Claire Kwan, MS

Kintara Therapeutics Inc.
Menlo Park, United States
GJ

Gregory Johnson, M.Sc.

Kintara Therapeutics Inc.
Victoria, Canada
RS

Richard Schwartz, MD

Kintara Therapeutics Inc.
Burlingame, United States

Poster Presenter(s)

John M. Langlands, PhD

Kintara Therapeutics
Vancouver, Canada

Author(s)

Dennis M. Brown, PhD

Valent Technologies, LLC
Menlo Park, United States
QY

Qunying Yang, MD,Ph.D.

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Guangzhou, China (People's Republic)
JL

Jia-Wei Li

Sun Yat Sen University Cancer Center
Guangzhuo, China (People's Republic)
ZhongPing Chen, MD,Ph.D.

Sun Yat-sen University Cancer Center
GuangZhou, China (People's Republic)
Hairong Wang, Bachelor

Neuro-oncology, Sun Yat-sen University Cancer Center
Guangzhou, Guangdong Province, China, China (People's Republic)
SW

Shao-xiong Wu, MD,Ph.D.

Sun Yat-sen University Cancer Center
Guangzhuo, China (People's Republic)

Author(s)

CG

Chengcheng Guo, MD,PhD

Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine
Guangzhou, China (People's Republic)
JC

JianGen Chen

Sun Yat-sen University Cancer Center
GuangZhou, China (People's Republic)

VAL-083 is a novel bi-functional DNA targeting agent that induces inter-strand DNA cross-links at N7-guanine, leading to DNA double-strand breaks and cell death. In vitro and in vivo studies have demonstrated VAL-083 circumvents MGMT-mediated chemoresistance and differentiates it from other therapies used in the treatment of GBM, including temozolomide (TMZ). VAL-083 also acts as a radiosensitizer against GBM cancer stem cells in vitro. A Phase 2 study was conducted to evaluate the safety and tolerability of VAL-083 when administered concurrently with radiation therapy (RT) in newly diagnosed MGMT unmethylated GBM. Stage 1 was a dose-escalation phase to confirm the dose of VAL-083 in this setting. Patients received VAL-083 at 20, 30, or 40 mg/m²/day x 3 days every 21 days in combination with standard radiation treatment (RT) (2 Gy/day, 5 days/week for 6 weeks). Stage 2 was an expansion phase to enroll up to 20 additional patients at the 30 mg/m²/day of VAL-083 with RT. A total of 29 patients were enrolled in the study and completed treatment, with 25 patients receiving 30 mg/m²/day VAL-083. The median number of cycles completed by all patients was 9 (range 2-13). Consistent with our prior experience, myelosuppression was the most common adverse event. Pharmacokinetics (Cmax and AUC) of VAL-083 were broadly linear with respect to dose, and drug half-life was 0.8 hrs. In a sub-group of patients, levels of VAL-083 in CSF were found to be at least as high as those in plasma. The median progression free survival (PFS) for all patients enrolled was 9.3 (95%CI: 6.4-12.0) months. Eighteen (18/29; 62.1%) patients have died, and median overall survival for all patients enrolled was 19.6 (95%CI: 14.0-22.4) months. These results support the potential benefit of VAL-083 as a treatment alternative against GBM tumors with MGMT-mediated resistance to TMZ. Clinicaltrials.gov: NCT03050736.