first in human study to evaluate azd9793 in participants with advanced or metastatic solid tumours

Conditions: Hepatocellular Carcinoma

Summary: this research is designed to determine if experimental treatment with azd9793, a t cell-engaging antibody that targets gpc3, is safe, tolerable and has anti-cancer activity in patients with advanced or metastatic solid tumours which are gpc3+.

this is a first-time in human, modular phase i/ii, open-label multicentre study of azd9793 monotherapy administered intravenously (module 1), or azd9793 monotherapy administered subcutaneously (module 2) in patients with advanced or metastatic solid tumours. each module contains dose-escalation (part a) and dose-expansion (part b).

Eligibility criteria:
key inclusion criteria: * age ≥ 18 at the time of signing the informed consent. * gpc3 positive tumour as determined by a central laboratory using an analytically validated ihc assay. * must have at least one measurable lesion according to response evaluation criteria in solid tumors (recist) v1.1 * eastern cooperative oncology group performance status (ecog ps): 0-1 at screening. * predicted life expectancy of ≥ 12 weeks. * adequate organ and bone marrow function measured within 28 days prior to first dose as defined by the protocol. * contraceptive use by men or women should be consistent with local regulations, as defined by the protocol. * confirmed advanced recurrent and/or metastatic and/or unresectable hcc, which is histopathologically proven based on the criteria established by the world health organization. * barcelona clinic liver cancer (bclc) stage b (that is not eligible for locoregional therapy) or stage c. * child-pugh score class a. * previous therapy: part a: patients who have received at least one prior line of standard systemic therapy for hcc as per nccn or other local scientific guidelines and for which a clinical study is the best option for next treatment based on prior response and/or tolerability and/or patient/investigator decision. part b: patients must not have received more than 1 prior line of systemic therapy in the advanced recurrent and/or metastatic setting. key exclusion criteria: * unresolved toxicity from prior anticancer therapy, including iraes, of common terminology criteria for adverse events (ctcae) grade ≥ 2 except for vitiligo, peripheral neuropathy related to prior anti-cancer therapy, alopecia, endocrine disorders that are controlled with replacement hormone therapy and asymptomatic laboratory abnormalities. * prior to enrolment, participation in another clinical study with an investigational product administered in the last 21 days or 5 half-lives whichever is shorter. * car-t cell therapy within the last 6 months prior to enrolment on this study. * known allergy or hypersensitivity to azd9793 or any of the excipients of the product as outlined in the ib. * requires chronic immunosuppressive therapy (including steroids \> 10 mg prednisone/day or equivalent). * prior treatment with any therapy that is targeted to gpc3. * received any therapy to treat cancer (including chemotherapy, biologics, cellular therapies) within 5 half-lives of an anticancer drug prior to the first dose of study treatment. * received radiation within 14 days; palliative radiation to reduce the risk of tumour lysis syndrome (tls) or crs/neurotoxicity in participants with bulky disease is permitted. * undergone a major surgical procedure within 14 days to allow adequate healing * experienced unacceptable cytokine release syndrome (crs) or immune effector cell associated neurotoxicity (icans) following prior t cell engagers (tce) or chimeric antigen receptor t (car-t) cell therapy. * previous history of hemophagocytic lymphohistiocytosis (hlh) / macrophage activation syndrome (mas). * active or prior documented autoimmune or inflammatory disorders within 3 years of start of treatment. * cardiac conditions as defined by the protocol. * history of thromboembolic event within the past 3 months prior to the scheduled first dose of study intervention. * central nervous system (cns) metastases or cns pathology, as defined by the protocol, within 3 months prior to consent. * infectious disease including active human immunodeficiency virus (hiv), and uncontrolled active systemic fungal, bacterial or other infection.

Keywords: glypican-3 gpc3 gpc3+ tumours t cell-engaging antibody tce azd9793 solid tumours hcc