1041P - Phase I open-label, dose escalation and expansion study of YH003, an anti-CD40 agonist monoclonal antibody in combination with toripalimab in patients (pts) with advanced solid tumours

Background

Agonistic CD40 antibodies have been shown to promote anti-tumour T cell responses and promising activity has been observed in advanced solid tumours. Here we report the results of a multicenter, open-label study of YH003 + Toripalimab in dose escalation for pts with advanced solid tumours.

Methods

This was a phase I dose-escalation and expansion study. Part 1 was dose-escalation stage using an accelerated “3+3” design. The primary objective of Part 1 was safety and tolerability and to identify a maximum tolerated dose (MTD). Patients with advanced solid tumours received YH003 by IV administration Q3W as monotherapy at 0.03, 0.1, 0.3, 1.0 and 3.0 mg/kg for the first cycle (21 days), then in combination with fixed-dose Toripalimab at 240 mg Q3W from cycle 2. Patients tolerating treatment and deriving benefit could continue treatment for up to 1 year.

Results

Between 29 Jul 2020 and 26 May 2022, 20 pts were treated in Part 1. A DLT (dose-limiting toxicity) was observed at 1.0 mg/kg dose level (grade 3 transaminitis) in 1 pt. The MTD was not reached. Among Part 1 pts, 13 (65%) had any grade treatment related adverse events (TRAEs). The most common (≥ 10%) TRAEs were infusion related reactions, pyrexia, fatigue, nausea, elevated AST/ALT. No Grade 3-5 TRAEs and treatment-related SAEs occurred. 8 pts had received prior immunotherapy (PD-1/PD-L1 or PD-1+CTLA-4). Among 16 pts assessable for response, 1 pt achieved a complete response (CR), another pt achieved a partial response (PR) and 3 pts achieved stable disease (SD). A pt with anti-PD1/anti-CTLA4 refractory ocular melanoma with liver metastases (0.1 mg/kg dose level) achieved PR at the first tumour assessment in week 10 and ultimately a CR after nearly 2 years of study treatment. YH003 was well tolerated up to 3.0 mg/kg dose levels when combined with Toripalimab. Combining safety and preliminary efficacy data, the recommended dose of YH003 for part 2 was 0.3 mg/kg.

Conclusions

YH003 was well tolerated up to 3.0 mg/kg dose levels when combined with Toripalimab, and 0.3mg/kg was deemed the RP2D. YH003 has shown encouraging antitumour activity in patients with advanced solid tumours.

Clinical trial identification

NCT04481009.

Editorial acknowledgement

Legal entity responsible for the study

Eucure (Beijing) Biopharma Co., Ltd.

Funding

Eucure (Beijing) Biopharma Co., Ltd.

Disclosure

B. Markman: Financial Interests, Personal, Advisory Board: Amgen, MSD, Bristol Myers Squibb, BeiGene, AstraZeneca. J. Coward: Financial Interests, Institutional, Research Funding: AstraZeneca. M. Millward: Financial Interests, Personal, Advisory Board: BeiGene Australia Pty Ltd, Bristol Myers Squibb Australia Pty Ltd, AstraZeneca Australia Pty Ltd, The Limbic, Eli Lilly Australia Pty Ltd, IQVIA Australia Pty Ltd, Amgen Australia Pty Ltd, Merck Pte Ltd, Pfizer Australia Pty Ltd, Guardant Health, Roche Products Pty Ltd; Financial Interests, Personal, Full or part-time Employment, Employee: University of Western Australia; Financial Interests, Personal, Other, Consultant: Linear Clinical Research; Financial Interests, Institutional, Local PI, Trial payments to Institution: Bristol Myers Squibb, Genentech/Roche, BeiGene, Eli Lilly, Albion Laboratories, Akeso Biopharma, AbbVie, Five Prime Therapeutics, Dizal Pharma, Maxinovel, Amgen, Atridia, INXMED, Alpine Immune Sciences, Turning Point Therapeutics, IMPACT Therapeutics, Kinnate Biopharma, Rely Therapeutics, GenFleet Therapeutics, Vivace Therapeutics, Eucure Biopahrma, InventisBio, Cullinan Oncology, Tyra Biosciences, Axelia Oncology; Non-Financial Interests, Other, Scientific Advisory Committee member: Thoracic Oncology Group Australasia. All other authors have declared no conflicts of interest.