EVT801 Is Well Tolerated, Elicits Disease Control in Advanced Ovarian Cancer

John Friend, MD

EVT801, a highly selective, small molecule, VEGFR3 TKI, was well tolerated in patients with advanced solid tumors, and patients with advanced ovarian cancer experienced a stable disease rate of 46%, according to data from a phase 1 trial (NCT05114668).¹

The study included 26 patients with 11 different tumor types, including colorectal cancer, renal cell carcinoma (RCC), and pancreatic cancer, though advanced ovarian cancer (n = 11) was the most common tumor type among patients included in the study. EVT801 was administered across 6 cohorts at doses ranging from 50 mg per day to 500 mg twice per day, and the majority of toxicities were mild/moderate and transient in nature.

The study’s safety review team concluded that the trial met its primary objective of safety/tolerability and determining the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), along with the secondary objectives of pharmacokinetics (PK) and preliminary antitumor activity. The MTD was established at 500 mg twice per day. Notably, 400 mg twice per day was identified as the RP2D under the condition that continuous monotherapy will be used in future clinical trials.

"We are extremely pleased that the primary and secondary end points of stage 1 of the phase 1 clinical trial have been met,” John Friend, MD, chief executive officer of Kazia Therapeutics, stated in a news release. “The signals of clinical activity, especially in patients with advanced ovarian cancer are highly encouraging as we continue to progress the clinical development program for EVT801 as a potential first-in-class VEGFR3 inhibitor. With a median survival time of less than 4 years, there is a large unmet need for new therapies in patients with high-grade serous ovarian cancer."

EVT801 is designed to target tumor angiogenesis, and based on preclinical data, Kazia Therapeutics—the agent’s developer—believes the VEGFR3 TKI has favorable immune activity through the reduction of immunosuppressive cells and no effect on the proliferation of CD3-positive T cells. Additionally, the agent could stabilize tumor blood vessels to minimize hypoxia and decrease the potential for metastatic spread.

The open-label phase 1 study evaluated the safety, tolerability, and PK of EVT801 in patients with advanced or metastatic solid tumors who were unresponsive to standard treatment or had no standard treatment available.

Patients needed to be at least 18 years of age with histologically confirmed advanced or metastatic solid tumors with measurable or evaluable disease per RECIST v1.1 criteria. An EGOG performance status of 0 or 1; a life expectancy greater than 3 months; and adequate organ and bone marrow function were required.2 In stage 2, patients will also need to have histologically confirmed advanced RCC (stage 2A) or advanced soft tissue sarcoma (stage 2B).

Key exclusion criteria include a recent history of antitumor therapy; unresolved toxicities from prior treatment to grade 2 or lower; central nervous system tumors; and clinically significant cardiac disease or impaired cardiac function.

Stage 1 of the study evaluated EVT801 at escalating doses. Stage 2 will evaluate the dose at the MTD/RP2D in patients with advanced solid tumors and in biomarker expansion cohorts. Among the 11 patients with ovarian cancer treated during stage 1, the mean age was 67 years (range, 56-76), and the median time from diagnosis was 9 years.¹

The final data from stage 1 and the next steps of development for EVT801 will be shared at an upcoming medical conference in the second half of 2024.

References

1. Kazia reports successful stage 1 completion of the EVT801 phase 1 clinical trial in advanced cancer patients. News release. Kazia Therapeutics. May 1, 2024. Accessed May 1, 2024. https://www.prnewswire.com/news-releases/kazia-reports-successful-stage-1-completion-of-the-evt801-phase-1-clinical-trial-in-advanced-cancer-patients-302133011.html
2. Safety, tolerability, and pharmacokinetics of EVT801 in patients with advanced solid tumours. ClinicalTrials.gov. Updated May 19, 2023. Accessed May 1, 2024. https://clinicaltrials.gov/study/NCT05114668