On October 23, 2023 Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused drug development company, reported that selected clinical data from the company’s ongoing Phase 1 clinical trial evaluating EVT801 in patients with advanced solid tumours was presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 (ESMO 2023) on Saturday, 21 October 2023 (Press release, Kazia Therapeutics, OCT 23, 2023, View Source [SID1234636250]).
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Professor Carlos A Gomez-Roca, (IUCT-Oncopole, Toulouse France) presented data from a correlation analysis of tumour biopsies from six (6) enrolled patients with high grade serous ovarian cancer (HGS-OC). To date, twenty (20) patients with advanced solid tumors have been dosed in in the ongoing Phase 1 clinical trial, and the trial has advanced to dose escalation cohort 6.
Key Points from the presentation:
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The hypothesis for EVT801’s mechanism of action involves three (3) sequential anti-cancer mechanisms, all of which are thought to contribute to the potential inhibition of tumour growth and metastasis:
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Preventing tumour growth by impairing both tumour angiogenesis and (lymph)angiogenesis, thereby stabilizing the tumour vasculature, reducing metastasis, and reducing hypoxia in the tumour microenvironment.
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Enhancing anti-cancer immunity as reflected by a decrease in immunosuppressive cytokines and cells in the circulation and tumour environment.
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Promoting T-cell infiltration into the tumour, ultimately supporting an enhanced and long-lasting anti-tumour immune response.
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In a data analysis of biopsies from six (6) HGS-OC patients, high levels of VEGFR3 expression tended to be correlated with the following:
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Higher levels of hypoxia;
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Increased immune checkpoint (PD1) resistance; and
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Negatively correlated with CD8 positive T-cells infiltration.
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While these findings would need to be confirmed in patients in other indications, these correlations are encouraging and suggest that patients with hypoxic HGS-OC tumours that are poorly infiltrated with CD8 positive T-cells and with high VEGFR3 expression may benefit from EVT801 treatment.
"In spite of recent advances in treatments for ovarian cancer, there is an extremely high rate of recurrence. The success of immune checkpoint inhibitors in other solid tumours has not carried through to high grade serous ovarian cancer. In data previously presented at AACR (Free AACR Whitepaper) 2023, we demonstrated a high prevalence of VEGFR-3 expression in HGS-OC tumours, and we have now presented data showing a positive correlation between VEGFR-3 expression and hypoxia and PD1 resistance signature and a negative correlation with CD8 positive T-cell infiltration," said Dr. John Friend, Chief Executive Officer of Kazia. "We look forward to completing dose escalation in stage 1 of the ongoing study and progressing to stage 2 of the Phase 1 Study ."